Materiały źródłowe

• #1 Lupus Nephritis from Pathogenesis to New Therapies: An Update

  https://www.mdpi.com/1422-0067/25/16/8981

  Lupus Nephritis (LN) still represents one of the most severe complications of Systemic Lupus Erythematosus (SLE) and a major risk factor for morbidity and mortality. […] However, over the last few years, several studies have paved the way for a deeper understanding of its pathogenetic mechanisms and more targeted treatments. […] The pathogenesis of LN is complex and multi-factorial. It involves a variety of extra- and intra-renal pathogenic mechanisms, resulting from genetic predisposition as well as environmental and hormonal factors. […] Over 100 susceptibility loci in the human genome are linked to SLE and LN. Genetic variants are involved in loss of tolerance against nuclear autoantigens, abnormal lymphocyte and complement function and kidney damage. […] The strongest LN genetic association relates to the major histocompatibility complex (MHC) region, with an increased risk due to amplified tissue inflammation (HLA-DR2 and HLA-DR15); on the other hand, different HLA alleles may exert a protective effect (HLA-DR4 and HLA-DR11).

• #2 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  Systemic lupus erythematosus (SLE) is the prototype of autoimmune disorders caused by a loss of tolerance to endogenous nuclear antigens triggering an aberrant autoimmune response targeting various tissues. […] Lupus nephritis (LN), a major cause of morbidity and mortality in patients with SLE, affects up to 60% of patients. […] The recent insights into the genetic and molecular basis of SLE and LN paved the way for newer therapies to be developed for these patients. […] Acknowledging that multiple extrarenal and intrarenal pathways contribute to kidney-specific autoimmunity and injury may help refine the individual therapeutic and prognostic characterization of such patients. […] The scope of this review is to provide an insight into the current knowledge of LN pathogenesis and future therapeutic strategies.

• #3

  https://journals.lww.com/jasn/fulltext/2013/09000/the_pathogenesis_of_lupus_nephritis.7.aspx

  Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. […] The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies.

• #4 Epidemiology, pathophysiology and management of Lupus Nephritis – Conquest Health

  https://conquest.health/epidemiology-pathophysiology-and-management-of-lupus-nephritis/

  Lupus nephritis (LN) is a form of glomerulonephritis that constitutes one of the most severe organ manifestations of the autoimmune disease systemic lupus erythematosus (SLE). […] The pathogenesis of LN involves extrarenal and intrarenal pathogenic mechanisms. Extrarenal influences include complicated genetic variation combinations that are unique to each patient, explaining the wide range of clinical symptoms. The nucleic acid content of nuclear particles from apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. The intrarenal pathology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which includes B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #5 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  SLE and LN pathogenesis clearly involve a genetic predisposition as first-degree relatives of patients with SLE are at higher risk of SLE and other autoimmune disorders. […] Over the past decades, with the advent of extensive genome-wide association studies, more than 100 susceptibility loci that were linked to SLE and LN were identified. […] Genes that are potentially involved in SLE pathogenesis can be broadly classified into four categories: genes involved in lymphocyte function, genes involved in innate immune signaling, genes involved in DNA clearance and complement pathway, and genes contributing to renal injury. […] In SLE and LN, the crosstalk between autoreactive B-cells and T-cells is essential. […] Signaling through type I IFN (interferon) receptor (IFNαRII) is a molecular hallmark of SLE and LN, and several single-nucleotide polymorphisms related to the genes involved in the downstream signal transduction pathways seem to be involved in the expression of IFN stimulated genes (ISGs) affecting key functions of innate and acquired immunity and, possibly, of resident renal cells.

• #6 Lupus Nephritis from Pathogenesis to New Therapies: An Update

  https://www.mdpi.com/1422-0067/25/16/8981

  Lupus Nephritis (LN) still represents one of the most severe complications of Systemic Lupus Erythematosus (SLE) and a major risk factor for morbidity and mortality. […] However, over the last few years, several studies have paved the way for a deeper understanding of its pathogenetic mechanisms and more targeted treatments. […] The pathogenesis of LN is complex and multi-factorial. It involves a variety of extra- and intra-renal pathogenic mechanisms, resulting from genetic predisposition as well as environmental and hormonal factors. […] Over 100 susceptibility loci in the human genome are linked to SLE and LN. Genetic variants are involved in loss of tolerance against nuclear autoantigens, abnormal lymphocyte and complement function and kidney damage. […] The strongest LN genetic association relates to the major histocompatibility complex (MHC) region, with an increased risk due to amplified tissue inflammation (HLA-DR2 and HLA-DR15); on the other hand, different HLA alleles may exert a protective effect (HLA-DR4 and HLA-DR11).

• #7 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  SLE and LN pathogenesis clearly involve a genetic predisposition as first-degree relatives of patients with SLE are at higher risk of SLE and other autoimmune disorders. […] Over the past decades, with the advent of extensive genome-wide association studies, more than 100 susceptibility loci that were linked to SLE and LN were identified. […] Genes that are potentially involved in SLE pathogenesis can be broadly classified into four categories: genes involved in lymphocyte function, genes involved in innate immune signaling, genes involved in DNA clearance and complement pathway, and genes contributing to renal injury. […] In SLE and LN, the crosstalk between autoreactive B-cells and T-cells is essential. […] Signaling through type I IFN (interferon) receptor (IFNαRII) is a molecular hallmark of SLE and LN, and several single-nucleotide polymorphisms related to the genes involved in the downstream signal transduction pathways seem to be involved in the expression of IFN stimulated genes (ISGs) affecting key functions of innate and acquired immunity and, possibly, of resident renal cells.

• #8 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  SLE and LN pathogenesis clearly involve a genetic predisposition as first-degree relatives of patients with SLE are at higher risk of SLE and other autoimmune disorders. […] Over the past decades, with the advent of extensive genome-wide association studies, more than 100 susceptibility loci that were linked to SLE and LN were identified. […] Genes that are potentially involved in SLE pathogenesis can be broadly classified into four categories: genes involved in lymphocyte function, genes involved in innate immune signaling, genes involved in DNA clearance and complement pathway, and genes contributing to renal injury. […] In SLE and LN, the crosstalk between autoreactive B-cells and T-cells is essential. […] Signaling through type I IFN (interferon) receptor (IFNαRII) is a molecular hallmark of SLE and LN, and several single-nucleotide polymorphisms related to the genes involved in the downstream signal transduction pathways seem to be involved in the expression of IFN stimulated genes (ISGs) affecting key functions of innate and acquired immunity and, possibly, of resident renal cells.

• #9 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  SLE and LN pathogenesis clearly involve a genetic predisposition as first-degree relatives of patients with SLE are at higher risk of SLE and other autoimmune disorders. […] Over the past decades, with the advent of extensive genome-wide association studies, more than 100 susceptibility loci that were linked to SLE and LN were identified. […] Genes that are potentially involved in SLE pathogenesis can be broadly classified into four categories: genes involved in lymphocyte function, genes involved in innate immune signaling, genes involved in DNA clearance and complement pathway, and genes contributing to renal injury. […] In SLE and LN, the crosstalk between autoreactive B-cells and T-cells is essential. […] Signaling through type I IFN (interferon) receptor (IFNαRII) is a molecular hallmark of SLE and LN, and several single-nucleotide polymorphisms related to the genes involved in the downstream signal transduction pathways seem to be involved in the expression of IFN stimulated genes (ISGs) affecting key functions of innate and acquired immunity and, possibly, of resident renal cells.

• #10 Lupus Nephritis from Pathogenesis to New Therapies: An Update

  https://www.mdpi.com/1422-0067/25/16/8981

  Lupus Nephritis (LN) still represents one of the most severe complications of Systemic Lupus Erythematosus (SLE) and a major risk factor for morbidity and mortality. […] However, over the last few years, several studies have paved the way for a deeper understanding of its pathogenetic mechanisms and more targeted treatments. […] The pathogenesis of LN is complex and multi-factorial. It involves a variety of extra- and intra-renal pathogenic mechanisms, resulting from genetic predisposition as well as environmental and hormonal factors. […] Over 100 susceptibility loci in the human genome are linked to SLE and LN. Genetic variants are involved in loss of tolerance against nuclear autoantigens, abnormal lymphocyte and complement function and kidney damage. […] The strongest LN genetic association relates to the major histocompatibility complex (MHC) region, with an increased risk due to amplified tissue inflammation (HLA-DR2 and HLA-DR15); on the other hand, different HLA alleles may exert a protective effect (HLA-DR4 and HLA-DR11).

• #11 Update on Lupus Nephritis Management – Renal and Urology News

  https://www.renalandurologynews.com/news/update-on-lupus-nephritis-management/

  Investigators are making strides in understanding the pathogenesis and management of lupus nephritis. […] Genetics play a role in lupus nephritis development and progression. Patients with lupus nephritis who have a high genetic load have increased odds for end-stage kidney disease and death, according to a study by Lars Rnnblom, MD, of Uppsala University in Sweden and colleagues. […] STAT4 and TLRI genes carry risk variants for lupus nephritis. A study found that smoking in the presence of the STAT4 risk gene variant increases the risk for nephritis. Other research suggests a common pathway underlying systemic lupus erythematosus and lupus nephritis. […] Decreases in species diversity in the intestinal microbiome may trigger lupus nephritis, according to a team led by Gregg J Silverman, MD, of New York University School of Medicine in New York, New York.

• #12 Lupus Nephritis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330369-overview

  Autoimmunity plays a major role in the pathogenesis of lupus nephritis. The immunologic mechanisms include production of autoantibodies directed against nuclear elements. Characteristics of the nephritogenic autoantibodies associated with lupus nephritis are as follows: […] These autoantibodies form pathogenic immune complexes intravascularly, which are deposited in glomeruli. Alternatively, autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils. […] The histologic type of lupus nephritis that develops depends on numerous factors, including the antigen specificity and other properties of the autoantibodies and the type of inflammatory response that is determined by other host factors. In more severe forms of lupus nephritis, proliferation of endothelial, mesangial, and epithelial cells and the production of matrix proteins lead to fibrosis.

• #13 Lupus Nephritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499817/

  Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE) a chronic autoimmune disease that causes inflammation and damage to multiple organ systems, with the kidneys as a primary target. […] The pathogenesis of lupus nephritis involves a combination of genetic, environmental, and immune system factors. The condition is primarily driven by a type III hypersensitivity reaction, which leads to the formation of immune complexes. Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies bind to DNA, which forms anti-dsDNA immune complexes. These immune complexes deposit in the mesangium, subendothelial, or subepithelial spaces near the glomerular basement membrane, triggering an inflammatory response. This activates the complement pathway, resulting in the influx of neutrophils and other inflammatory cells, which contribute to the development of lupus nephritis.

• #14 Mechanisms of tissue injury in lupus nephritis | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar3528

  Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occurs in approximately 50% of lupus patients. […] Much of what is known about pathogenic factors in tissue damage in lupus nephritis was derived from studies of murine models of lupus, with confirmation as possible in humans. […] The presence of autoantibodies is a requirement for development of lupus nephritis. Antibodies to dsDNA/nucleosomes are most closely linked with development of nephritis, although what separates pathogenic from nonpathogenic anti-dsDNA antibodies is not clear. Pathogenic anti-dsDNA antibodies deposit as immune complexes.

• #15 Lupus Nephritis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330369-overview

  Autoimmunity plays a major role in the pathogenesis of lupus nephritis. The immunologic mechanisms include production of autoantibodies directed against nuclear elements. Characteristics of the nephritogenic autoantibodies associated with lupus nephritis are as follows: […] These autoantibodies form pathogenic immune complexes intravascularly, which are deposited in glomeruli. Alternatively, autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils. […] The histologic type of lupus nephritis that develops depends on numerous factors, including the antigen specificity and other properties of the autoantibodies and the type of inflammatory response that is determined by other host factors. In more severe forms of lupus nephritis, proliferation of endothelial, mesangial, and epithelial cells and the production of matrix proteins lead to fibrosis.

• #16 Lupus nephritis

  https://www.kidneypathology.com/English_version/Lupus_nephritis.html

  Lupus nephritis is a type-3 hypersensitivity reaction. This occurs when immune complexes are formed. The characteristics of the autoantibodies in relevance to lupus nephritis are: i) Anti-dsDNA antibodies may cross-react with the glomerular basement membrane; ii) Higher-affinity autoantibodies may result in intravascular immune complexes that get deposited in glomeruli; iii) Cationic autoantibodies have a greater affinity for the anionic basement membrane; iiii) Activation of complements by autoantibodies of certain isotypes. These autoantibodies make immune complexes within the vessels that are deposited in glomeruli. Alternatively, autoantibodies may form immune complexes in situ by binding to antigens that are already located in the glomerular basement membrane. Immune complexes induce an inflammatory response by the activation of the complement system and recruitment of inflammatory cells. Glomerular thrombosis is another phenomenon that plays a part in the pathogenesis of lupus nephritis particularly in patients with antiphospholipid syndrome and is believed to be the result of an interaction between antibodies and negatively charged phospholipid-proteins.

• #17 Lupus Nephritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499817/

  Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE) a chronic autoimmune disease that causes inflammation and damage to multiple organ systems, with the kidneys as a primary target. […] The pathogenesis of lupus nephritis involves a combination of genetic, environmental, and immune system factors. The condition is primarily driven by a type III hypersensitivity reaction, which leads to the formation of immune complexes. Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies bind to DNA, which forms anti-dsDNA immune complexes. These immune complexes deposit in the mesangium, subendothelial, or subepithelial spaces near the glomerular basement membrane, triggering an inflammatory response. This activates the complement pathway, resulting in the influx of neutrophils and other inflammatory cells, which contribute to the development of lupus nephritis.

• #18 Lupus nephritis – Wikipedia

  https://en.wikipedia.org/wiki/Lupus_nephritis

  Lupus nephritis develops through a mix of genetic, environmental, and immune system influences. […] It is mainly caused by a type III hypersensitivity reaction, where antibodies against double-stranded DNA (anti-dsDNA) form immune complexes with DNA. […] These complexes build up in areas of the kidney like the mesangium and around the glomerular basement membrane. […] This triggers the complement system, bringing in neutrophils and other immune cells, which cause inflammation and kidney damage. […] The pathophysiology of lupus nephritis has autoimmunity contributing significantly. […] Autoantibodies direct themselves against nuclear elements. […] The characteristics of nephritogenic autoantibodies (lupus nephritis) are antigen specificity directed at nucleosome, high affinity autoantibodies form intravascular immune complexes, and autoantibodies of certain isotypes activate complement.

• #19 Lupus Nephritis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330369-overview

  Autoimmunity plays a major role in the pathogenesis of lupus nephritis. The immunologic mechanisms include production of autoantibodies directed against nuclear elements. Characteristics of the nephritogenic autoantibodies associated with lupus nephritis are as follows: […] These autoantibodies form pathogenic immune complexes intravascularly, which are deposited in glomeruli. Alternatively, autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils. […] The histologic type of lupus nephritis that develops depends on numerous factors, including the antigen specificity and other properties of the autoantibodies and the type of inflammatory response that is determined by other host factors. In more severe forms of lupus nephritis, proliferation of endothelial, mesangial, and epithelial cells and the production of matrix proteins lead to fibrosis.

• #20 Lupus nephritis: Diagnosis and classification – UpToDate

  https://www.uptodate.com/contents/lupus-nephritis-diagnosis-and-classification/print

  Anti-dsDNA immune complex formation – These immune complexes are primarily composed of DNA and anti-dsDNA. […] The immune deposits in LN can occur in the mesangium, subendothelial, and/or subepithelial compartments of the glomerulus. […] The degree and nature of immune deposition as well as the response to the deposits determine whether the patient develops mild disease limited to the mesangium or a more severe focal or diffuse proliferative glomerulonephritis. […] Immune complex deposition can activate other arms of the inflammatory response. […] Although kidney disease is primarily due to anti-dsDNA complexes, some data suggest that autoantibodies against C1q, a complement component, may correlate with LN. […] The induction of nephritis by anti-dsDNA may not require immune complex formation.

• #21 Lupus Nephritis from Pathogenesis to New Therapies: An Update

  https://www.mdpi.com/1422-0067/25/16/8981

  The role of autoantibodies and IC production in kidney inflammation is well known. […] Stimulation of autoantibodies requires a source of extracellular DNA in an immunologically accessible form, such as extracellular DNA emerging from dead and dying cells due to abnormal apoptosis. […] Autoantibodies directed against nuclear and cellular antigens lead to the formation of ICs, which accumulate in both glomeruli and interstitium, activating complement and recruiting immune cells. […] Complement plays a dual role in LN pathogenesis. Effective clearance of ICs by early complement components protects against the development of LN, as shown by the consequences of genetic defects in complement; however, its uncontrolled activation promotes kidney damage in SLE. […] Vitamin D deficiency (serum 25-hydroxyvitamin D < 15 ng/mL) is common in SLE due to a variety of reasons: reduced sun exposure to avoid photosensitivity, possible interference by glucocorticoids (GC) and hydroxychloroquine (HCQ), presence of autoantibodies against it.

• #22 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  Neutrophils emerged as important players in SLE and LN pathogenesis, the expression of neutrophil-specific genes being prevalent and correlating with disease activity. […] Neutrophils are the first line of defense mechanism against infections, but also important contributors to autoimmunity through a unique form of cell death called NETosis (neutrophil extracellular trap). […] The complement system has a dual role in the pathogenesis of SLE, especially LN. […] The complement activation through both classical and alternate pathways is an important mediator to autoantibody-mediated renal injury. […] The progress that has been made in the understanding of LN pathogenesis created the premises for new therapeutic agents to be developed. […] Currently, several molecular pathways are being explored as potential therapeutic targets in LN, thus offering the possibility to better individualize patient management.

• #23 Lupus Nephritis from Pathogenesis to New Therapies: An Update

  https://www.mdpi.com/1422-0067/25/16/8981

  The role of autoantibodies and IC production in kidney inflammation is well known. […] Stimulation of autoantibodies requires a source of extracellular DNA in an immunologically accessible form, such as extracellular DNA emerging from dead and dying cells due to abnormal apoptosis. […] Autoantibodies directed against nuclear and cellular antigens lead to the formation of ICs, which accumulate in both glomeruli and interstitium, activating complement and recruiting immune cells. […] Complement plays a dual role in LN pathogenesis. Effective clearance of ICs by early complement components protects against the development of LN, as shown by the consequences of genetic defects in complement; however, its uncontrolled activation promotes kidney damage in SLE. […] Vitamin D deficiency (serum 25-hydroxyvitamin D < 15 ng/mL) is common in SLE due to a variety of reasons: reduced sun exposure to avoid photosensitivity, possible interference by glucocorticoids (GC) and hydroxychloroquine (HCQ), presence of autoantibodies against it.

• #24 Lupus Nephritis from Pathogenesis to New Therapies: An Update

  https://www.mdpi.com/1422-0067/25/16/8981

  The role of autoantibodies and IC production in kidney inflammation is well known. […] Stimulation of autoantibodies requires a source of extracellular DNA in an immunologically accessible form, such as extracellular DNA emerging from dead and dying cells due to abnormal apoptosis. […] Autoantibodies directed against nuclear and cellular antigens lead to the formation of ICs, which accumulate in both glomeruli and interstitium, activating complement and recruiting immune cells. […] Complement plays a dual role in LN pathogenesis. Effective clearance of ICs by early complement components protects against the development of LN, as shown by the consequences of genetic defects in complement; however, its uncontrolled activation promotes kidney damage in SLE. […] Vitamin D deficiency (serum 25-hydroxyvitamin D < 15 ng/mL) is common in SLE due to a variety of reasons: reduced sun exposure to avoid photosensitivity, possible interference by glucocorticoids (GC) and hydroxychloroquine (HCQ), presence of autoantibodies against it.

• #25 Lupus nephritis: Diagnosis and classification – UpToDate

  https://www.uptodate.com/contents/lupus-nephritis-diagnosis-and-classification/print

  Lupus nephritis (LN) typically develops early in the disease course. […] The pathogenesis of LN is complicated. The pathogenesis may involve the expression of genes, both in the peripheral blood as well as in the kidneys, leading to neutrophil activation and increased expression of interferon and upregulation of myeloid cell and proinflammatory transcriptomes. […] Neutrophils and dying neutrophils may release neutrophil extracellular traps (NETs) composed of chromatin, histones, and immunostimulatory proteins that become a source of nuclear antigens allowing antigen-specific autoantibody production. […] Complement activation in LN may damage the kidney through endothelial damage and enhancement of kidney inflammation. […] The pattern of glomerular injury seen in SLE (and in other immune complex-mediated glomerular diseases) is generally related to the site of formation of the immune deposits, which are primarily due to anti-double-stranded DNA (anti-dsDNA or anti-DNA) antibodies.

• #26 Lupus Nephritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499817/

  Immune system dysregulation in SLE has been well-understood for many decades. Lupus nephritis is a type III hypersensitivity reaction that results from the formation of immune complexes. Autoimmunity has a crucial role in the development of lupus nephritis, leading to the production of autoantibodies directed against nuclear elements. […] These autoantibodies form immune complexes within blood vessels, which are then deposited in the glomeruli. Additionally, autoantibodies may bind to glomerular basement membrane antigens, forming immune complexes in situ. These immune complexes trigger an inflammatory response by activating the complement system and recruiting inflammatory cells. […] Lupus nephritis can progress in severity over time through a phenomenon called „epitope spreading,” where autoantibodies initially recognize one epitope, then expand to recognize additional epitopes on the same molecule, followed by recognition of epitopes on other molecules. […] Uncontrolled complement activation also contributes to the pathogenesis of SLE, involving all 3 complement pathways. Low C3 levels are more strongly correlated with lupus nephritis than low C4 levels, highlighting the significance of the alternative complement pathway in this process.

• #27 Lupus Nephritis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25699

  Lupus nephritis can progress in severity over time through a phenomenon called „epitope spreading,” where autoantibodies initially recognize one epitope, then expand to recognize additional epitopes on the same molecule, followed by recognition of epitopes on other molecules. This process involves both intramolecular and intermolecular epitope spreading. Initially, deposits form in the mesangium (class I/II), but as epitope spreading occurs, additional antibodies are produced, leading to deposits in the subendothelial and subepithelial compartments (class III/IV). […] Anti-dsDNA antibodies are a hallmark of SLE, with apoptotic cells providing the extracellular DNA against which these antibodies are directed. These autoantibodies form immune complexes with nucleosomes that are deposited in the glomeruli and interstitial space. Additionally, anti-dsDNA antibodies activate the complement system and immune cells, particularly B lymphocytes and dendritic cells. However, anti-enolase-1 and anti-histone-2 antibodies may correlate more strongly with lupus nephritis than anti-dsDNA antibodies. […] Uncontrolled complement activation also contributes to the pathogenesis of SLE, involving all 3 complement pathways. Low C3 levels are more strongly correlated with lupus nephritis than low C4 levels, highlighting the significance of the alternative complement pathway in this process.

• #28 Mechanisms of tissue injury in lupus nephritis | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar3528

  A recent series of investigations implicates a third mechanism, anti-dsDNA/chromatin antibodies binding to nucleosomes/DNA present in the glomerular matrix, as the most compelling. […] Complement has a dual role in lupus. Deposition of complement proteins in glomeruli is a key feature of lupus nephritis. There is strong evidence that complement activation is deleterious in lupus nephritis. […] Recent findings implicate the alternative complement pathway as a key component of complement-mediated damage in lupus nephritis. […] Blocking the alternative complement pathway either genetically or pharmacologically leads to significantly decreased severity of renal disease in murine lupus models. […] Another mechanism by which ICs may lead to tissue damage is via activation of activating FcRs, upon binding of immunoglobulin Fc regions by FcR-expressing cells.

• #29 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  Neutrophils emerged as important players in SLE and LN pathogenesis, the expression of neutrophil-specific genes being prevalent and correlating with disease activity. […] Neutrophils are the first line of defense mechanism against infections, but also important contributors to autoimmunity through a unique form of cell death called NETosis (neutrophil extracellular trap). […] The complement system has a dual role in the pathogenesis of SLE, especially LN. […] The complement activation through both classical and alternate pathways is an important mediator to autoantibody-mediated renal injury. […] The progress that has been made in the understanding of LN pathogenesis created the premises for new therapeutic agents to be developed. […] Currently, several molecular pathways are being explored as potential therapeutic targets in LN, thus offering the possibility to better individualize patient management.

• #30 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  Neutrophils emerged as important players in SLE and LN pathogenesis, the expression of neutrophil-specific genes being prevalent and correlating with disease activity. […] Neutrophils are the first line of defense mechanism against infections, but also important contributors to autoimmunity through a unique form of cell death called NETosis (neutrophil extracellular trap). […] The complement system has a dual role in the pathogenesis of SLE, especially LN. […] The complement activation through both classical and alternate pathways is an important mediator to autoantibody-mediated renal injury. […] The progress that has been made in the understanding of LN pathogenesis created the premises for new therapeutic agents to be developed. […] Currently, several molecular pathways are being explored as potential therapeutic targets in LN, thus offering the possibility to better individualize patient management.

• #31 Lupus nephritis: Diagnosis and classification – UpToDate

  https://www.uptodate.com/contents/lupus-nephritis-diagnosis-and-classification/print

  Lupus nephritis (LN) typically develops early in the disease course. […] The pathogenesis of LN is complicated. The pathogenesis may involve the expression of genes, both in the peripheral blood as well as in the kidneys, leading to neutrophil activation and increased expression of interferon and upregulation of myeloid cell and proinflammatory transcriptomes. […] Neutrophils and dying neutrophils may release neutrophil extracellular traps (NETs) composed of chromatin, histones, and immunostimulatory proteins that become a source of nuclear antigens allowing antigen-specific autoantibody production. […] Complement activation in LN may damage the kidney through endothelial damage and enhancement of kidney inflammation. […] The pattern of glomerular injury seen in SLE (and in other immune complex-mediated glomerular diseases) is generally related to the site of formation of the immune deposits, which are primarily due to anti-double-stranded DNA (anti-dsDNA or anti-DNA) antibodies.

• #32 SLE & Lupus Nephritis: Pathophysiology & Diagnosis – GlomCon (pubs)

  https://pubs.glomcon.org/sle-lupus-nephritis-pathophysiology-diagnosis/

  The critical step in lupus nephritis is the occurrence of antigen-antibody complexes in the kidney […] Recently, it has been demonstrated that antibodies may form at tertiary lymphoid tissues within the kidney itself. […] These antigen-antibody complexes then set off an inflammatory cascade, which recruits neutrophils. […] These neutrophils produce inflammatory cytokines, apoptosis, and make NETs, resulting in further antigen exposure within the kidney.

• #33 The Pathogenesis of Lupus Nephritis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3752952/

  Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. […] The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. […] The nucleic acid content of nuclear particles from netting or apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. […] The intrarenal etiology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which include B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #34 Epidemiology, pathophysiology and management of Lupus Nephritis – Conquest Health

  https://conquest.health/epidemiology-pathophysiology-and-management-of-lupus-nephritis/

  Lupus nephritis (LN) is a form of glomerulonephritis that constitutes one of the most severe organ manifestations of the autoimmune disease systemic lupus erythematosus (SLE). […] The pathogenesis of LN involves extrarenal and intrarenal pathogenic mechanisms. Extrarenal influences include complicated genetic variation combinations that are unique to each patient, explaining the wide range of clinical symptoms. The nucleic acid content of nuclear particles from apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. The intrarenal pathology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which includes B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #35 Lupus nephritis: Diagnosis and classification – UpToDate

  https://www.uptodate.com/contents/lupus-nephritis-diagnosis-and-classification/print

  Neutrophils and NETs may add to antigen-specific autoantibody production facilitating inflammation, endothelial damage, and local interferon alpha production in the kidney. […] A variety of genes and genetic factors reportedly predispose patients to the development of SLE and influence the clinical picture of kidney disease in SLE. […] The increased frequency and severity of LN among African Americans has led to the examination of genetic factors that might predispose them to LN.

• #36 Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/82/8/999

  Neutrophils, particularly low-density granulocytes, and neutrophil products, including neutrophil extracellular traps (NETs), remain a potential source of stimulatory nucleic acid and innate immune system activation. […] Serum NET levels are elevated in patients with lupus nephritis and correlate with proteinuria, and blood and tissues contain increased NETs in association with IL-33, a member of the IL-1 cytokine family, in active lupus. […] The specific targets of the autoimmune response in SLE include intracellular and intranuclear particles that include nucleic acid and nucleic acid-binding proteins. […] Lupus nephritis is understood to depend on deposition of autoantibodies, often in the form of immune complexes, in renal glomeruli, accompanied by complement activation and recruitment of neutrophils.

• #37 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  The type I interferon system is an essential component of innate and adaptive immunity that, for decades, was regarded as the main line of defense against viral infections. […] However, the type I IFN system has additional important roles in the pathogenesis of autoimmune disorders, especially in SLE and LN. […] The driver of IFN-α in LN are the interferogenic immune complexes (ICs) containing nucleic acids (DNA/RNA). […] The pathogenic relevance of type I IFN system was explored clinically as anifrolumab, a type I IFN receptor antagonist, substantially reduced disease activity in patients with moderate to severe SLE. […] Renal injury in LN occurs through either circulating immune complex deposition, autoantibodies binding to “planted” glomerular antigens, or in situ immune complex formation within glomeruli.

• #38 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  SLE and LN pathogenesis clearly involve a genetic predisposition as first-degree relatives of patients with SLE are at higher risk of SLE and other autoimmune disorders. […] Over the past decades, with the advent of extensive genome-wide association studies, more than 100 susceptibility loci that were linked to SLE and LN were identified. […] Genes that are potentially involved in SLE pathogenesis can be broadly classified into four categories: genes involved in lymphocyte function, genes involved in innate immune signaling, genes involved in DNA clearance and complement pathway, and genes contributing to renal injury. […] In SLE and LN, the crosstalk between autoreactive B-cells and T-cells is essential. […] Signaling through type I IFN (interferon) receptor (IFNαRII) is a molecular hallmark of SLE and LN, and several single-nucleotide polymorphisms related to the genes involved in the downstream signal transduction pathways seem to be involved in the expression of IFN stimulated genes (ISGs) affecting key functions of innate and acquired immunity and, possibly, of resident renal cells.

• #39 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  The type I interferon system is an essential component of innate and adaptive immunity that, for decades, was regarded as the main line of defense against viral infections. […] However, the type I IFN system has additional important roles in the pathogenesis of autoimmune disorders, especially in SLE and LN. […] The driver of IFN-α in LN are the interferogenic immune complexes (ICs) containing nucleic acids (DNA/RNA). […] The pathogenic relevance of type I IFN system was explored clinically as anifrolumab, a type I IFN receptor antagonist, substantially reduced disease activity in patients with moderate to severe SLE. […] Renal injury in LN occurs through either circulating immune complex deposition, autoantibodies binding to “planted” glomerular antigens, or in situ immune complex formation within glomeruli.

• #40 Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

  https://www.mdpi.com/1422-0067/22/7/3766

  The type I interferon system is an essential component of innate and adaptive immunity that, for decades, was regarded as the main line of defense against viral infections. […] However, the type I IFN system has additional important roles in the pathogenesis of autoimmune disorders, especially in SLE and LN. […] The driver of IFN-α in LN are the interferogenic immune complexes (ICs) containing nucleic acids (DNA/RNA). […] The pathogenic relevance of type I IFN system was explored clinically as anifrolumab, a type I IFN receptor antagonist, substantially reduced disease activity in patients with moderate to severe SLE. […] Renal injury in LN occurs through either circulating immune complex deposition, autoantibodies binding to “planted” glomerular antigens, or in situ immune complex formation within glomeruli.

• #41 New insights into the role of renal resident cells in the pathogenesis of lupus nephritis

  https://www.kjim.org/journal/view.php?number=170008

  Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. […] In this review, we describe recent advances in the role of renal resident cells, including podocytes, mesangial cells, and epithelial cells, in the pathogenesis of lupus nephritis. […] Recent evidence supports a direct role for renal resident cells, including podocytes, mesangial cells, and tubular epithelial cells, in the development of lupus nephritis. […] Podocyte injury is common in patients with lupus nephritis, as shown in a large cohort study of patients with renal-biopsy-proven lupus nephritis. […] Several lines of evidence support the role of podocytes in the pathogenesis of lupus nephritis.

• #42

  https://journals.lww.com/co-rheumatology/fulltext/2023/03000/pathogenesis_of_lupus_nephritis__the_contribution.7.aspx

  Lupus nephritis is associated with significant mortality and morbidity. We lack effective therapeutics and biomarkers mostly because of our limited understanding of its complex pathogenesis. […] Recent studies have identified distinct roles for each resident kidney cell in the pathogenesis of lupus nephritis. Podocytes share many elements of innate and adaptive immune cells and they can present antigens and participate in the formation of crescents in coordination with parietal epithelial cells. Mesangial cells produce pro-inflammatory cytokines and secrete extracellular matrix contributing to glomerular fibrosis. Tubular epithelial cells modulate the milieu of the interstitium to promote T cell infiltration and formation of tertiary lymphoid organs. Modulation of specific genes in kidney resident cells can ward off the effectors of the autoimmune response including autoantibodies, cytokines and immune cells.

• #43

  https://journals.lww.com/co-rheumatology/fulltext/2023/03000/pathogenesis_of_lupus_nephritis__the_contribution.7.aspx

  Lupus nephritis is associated with significant mortality and morbidity. We lack effective therapeutics and biomarkers mostly because of our limited understanding of its complex pathogenesis. […] Recent studies have identified distinct roles for each resident kidney cell in the pathogenesis of lupus nephritis. Podocytes share many elements of innate and adaptive immune cells and they can present antigens and participate in the formation of crescents in coordination with parietal epithelial cells. Mesangial cells produce pro-inflammatory cytokines and secrete extracellular matrix contributing to glomerular fibrosis. Tubular epithelial cells modulate the milieu of the interstitium to promote T cell infiltration and formation of tertiary lymphoid organs. Modulation of specific genes in kidney resident cells can ward off the effectors of the autoimmune response including autoantibodies, cytokines and immune cells.

• #44 Pathogenesis of lupus nephritis: the contribution of immune and kidney resident cells

  https://research.bidmc.org/george-tsokos/publications/pathogenesis-lupus-nephritis-contribution-immune-and-kidney-resident-cells

  Lupus nephritis is associated with significant mortality and morbidity. […] We aim to present an overview of the recent advances in the field to gain a deeper understanding of the underlying cellular and molecular mechanisms involved in lupus nephritis pathogenesis. […] Recent studies have identified distinct roles for each resident kidney cell in the pathogenesis of lupus nephritis. Podocytes share many elements of innate and adaptive immune cells and they can present antigens and participate in the formation of crescents in coordination with parietal epithelial cells. Mesangial cells produce pro-inflammatory cytokines and secrete extracellular matrix contributing to glomerular fibrosis. Tubular epithelial cells modulate the milieu of the interstitium to promote T cell infiltration and formation of tertiary lymphoid organs. Modulation of specific genes in kidney resident cells can ward off the effectors of the autoimmune response including autoantibodies, cytokines and immune cells.

• #45

  https://journals.lww.com/co-rheumatology/fulltext/2023/03000/pathogenesis_of_lupus_nephritis__the_contribution.7.aspx

  Lupus nephritis is associated with significant mortality and morbidity. We lack effective therapeutics and biomarkers mostly because of our limited understanding of its complex pathogenesis. […] Recent studies have identified distinct roles for each resident kidney cell in the pathogenesis of lupus nephritis. Podocytes share many elements of innate and adaptive immune cells and they can present antigens and participate in the formation of crescents in coordination with parietal epithelial cells. Mesangial cells produce pro-inflammatory cytokines and secrete extracellular matrix contributing to glomerular fibrosis. Tubular epithelial cells modulate the milieu of the interstitium to promote T cell infiltration and formation of tertiary lymphoid organs. Modulation of specific genes in kidney resident cells can ward off the effectors of the autoimmune response including autoantibodies, cytokines and immune cells.

• #46 New insights into the role of renal resident cells in the pathogenesis of lupus nephritis

  https://www.kjim.org/journal/view.php?number=170008

  Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. […] In this review, we describe recent advances in the role of renal resident cells, including podocytes, mesangial cells, and epithelial cells, in the pathogenesis of lupus nephritis. […] Recent evidence supports a direct role for renal resident cells, including podocytes, mesangial cells, and tubular epithelial cells, in the development of lupus nephritis. […] Podocyte injury is common in patients with lupus nephritis, as shown in a large cohort study of patients with renal-biopsy-proven lupus nephritis. […] Several lines of evidence support the role of podocytes in the pathogenesis of lupus nephritis.

• #47 New insights into the role of renal resident cells in the pathogenesis of lupus nephritis

  https://www.kjim.org/journal/view.php?number=170008

  The production of type I IFN by renal resident cells, including mesangial cells, may aggravate autoimmune kidney diseases. […] Mesangial cells have also been implicated in the pathogenesis of lupus nephritis. […] Renal tubular epithelial cells are another type of renal resident cell likely to be involved in the pathophysiology of lupus nephritis. […] Identification of a common intracellular pathway that mediates not only aberrant immune cell activation related to autoimmunity but also podocyte dysfunction, will lead to a better understanding of the pathogenesis of lupus nephritis.

• #48 New insights into the role of renal resident cells in the pathogenesis of lupus nephritis

  https://www.kjim.org/journal/view.php?number=170008

  The production of type I IFN by renal resident cells, including mesangial cells, may aggravate autoimmune kidney diseases. […] Mesangial cells have also been implicated in the pathogenesis of lupus nephritis. […] Renal tubular epithelial cells are another type of renal resident cell likely to be involved in the pathophysiology of lupus nephritis. […] Identification of a common intracellular pathway that mediates not only aberrant immune cell activation related to autoimmunity but also podocyte dysfunction, will lead to a better understanding of the pathogenesis of lupus nephritis.

• #49 SLE & Lupus Nephritis: Pathophysiology & Diagnosis – GlomCon (pubs)

  https://pubs.glomcon.org/sle-lupus-nephritis-pathophysiology-diagnosis/

  The critical step in lupus nephritis is the occurrence of antigen-antibody complexes in the kidney […] Recently, it has been demonstrated that antibodies may form at tertiary lymphoid tissues within the kidney itself. […] These antigen-antibody complexes then set off an inflammatory cascade, which recruits neutrophils. […] These neutrophils produce inflammatory cytokines, apoptosis, and make NETs, resulting in further antigen exposure within the kidney.

• #50 The Pathogenesis of Lupus Nephritis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3752952/

  Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. […] The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. […] The nucleic acid content of nuclear particles from netting or apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. […] The intrarenal etiology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which include B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #51 The Pathogenesis of Lupus Nephritis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3752952/

  Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. […] The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. […] The nucleic acid content of nuclear particles from netting or apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. […] The intrarenal etiology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which include B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #52 Epidemiology, pathophysiology and management of Lupus Nephritis – Conquest Health

  https://conquest.health/epidemiology-pathophysiology-and-management-of-lupus-nephritis/

  Lupus nephritis (LN) is a form of glomerulonephritis that constitutes one of the most severe organ manifestations of the autoimmune disease systemic lupus erythematosus (SLE). […] The pathogenesis of LN involves extrarenal and intrarenal pathogenic mechanisms. Extrarenal influences include complicated genetic variation combinations that are unique to each patient, explaining the wide range of clinical symptoms. The nucleic acid content of nuclear particles from apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. The intrarenal pathology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which includes B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #53 The Pathogenesis of Lupus Nephritis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3752952/

  Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. […] The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. […] The nucleic acid content of nuclear particles from netting or apoptotic neutrophils activates innate and adaptive immunity by TLR7 and TLR9, which triggers an IFN-mediated antiviral host defense program that accounts for many of the nonspecific SLE symptoms. […] The intrarenal etiology of LN involves antibody binding to intrarenal nuclear autoantigens, local complement, and FcR activation. Tertiary lymph follicles, to some degree, form inside the kidney, which include B cells with local proinflammatory effects as well as plasma cells that secrete autoantibody inside the kidney.

• #54 Lupus Nephritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499817/

  Immune system dysregulation in SLE has been well-understood for many decades. Lupus nephritis is a type III hypersensitivity reaction that results from the formation of immune complexes. Autoimmunity has a crucial role in the development of lupus nephritis, leading to the production of autoantibodies directed against nuclear elements. […] These autoantibodies form immune complexes within blood vessels, which are then deposited in the glomeruli. Additionally, autoantibodies may bind to glomerular basement membrane antigens, forming immune complexes in situ. These immune complexes trigger an inflammatory response by activating the complement system and recruiting inflammatory cells. […] Lupus nephritis can progress in severity over time through a phenomenon called „epitope spreading,” where autoantibodies initially recognize one epitope, then expand to recognize additional epitopes on the same molecule, followed by recognition of epitopes on other molecules. […] Uncontrolled complement activation also contributes to the pathogenesis of SLE, involving all 3 complement pathways. Low C3 levels are more strongly correlated with lupus nephritis than low C4 levels, highlighting the significance of the alternative complement pathway in this process.

• #55 Lupus Nephritis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25699

  Lupus nephritis can progress in severity over time through a phenomenon called „epitope spreading,” where autoantibodies initially recognize one epitope, then expand to recognize additional epitopes on the same molecule, followed by recognition of epitopes on other molecules. This process involves both intramolecular and intermolecular epitope spreading. Initially, deposits form in the mesangium (class I/II), but as epitope spreading occurs, additional antibodies are produced, leading to deposits in the subendothelial and subepithelial compartments (class III/IV). […] Anti-dsDNA antibodies are a hallmark of SLE, with apoptotic cells providing the extracellular DNA against which these antibodies are directed. These autoantibodies form immune complexes with nucleosomes that are deposited in the glomeruli and interstitial space. Additionally, anti-dsDNA antibodies activate the complement system and immune cells, particularly B lymphocytes and dendritic cells. However, anti-enolase-1 and anti-histone-2 antibodies may correlate more strongly with lupus nephritis than anti-dsDNA antibodies. […] Uncontrolled complement activation also contributes to the pathogenesis of SLE, involving all 3 complement pathways. Low C3 levels are more strongly correlated with lupus nephritis than low C4 levels, highlighting the significance of the alternative complement pathway in this process.

• #56 Lupus Nephritis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25699

  Lupus nephritis can progress in severity over time through a phenomenon called „epitope spreading,” where autoantibodies initially recognize one epitope, then expand to recognize additional epitopes on the same molecule, followed by recognition of epitopes on other molecules. This process involves both intramolecular and intermolecular epitope spreading. Initially, deposits form in the mesangium (class I/II), but as epitope spreading occurs, additional antibodies are produced, leading to deposits in the subendothelial and subepithelial compartments (class III/IV). […] Anti-dsDNA antibodies are a hallmark of SLE, with apoptotic cells providing the extracellular DNA against which these antibodies are directed. These autoantibodies form immune complexes with nucleosomes that are deposited in the glomeruli and interstitial space. Additionally, anti-dsDNA antibodies activate the complement system and immune cells, particularly B lymphocytes and dendritic cells. However, anti-enolase-1 and anti-histone-2 antibodies may correlate more strongly with lupus nephritis than anti-dsDNA antibodies. […] Uncontrolled complement activation also contributes to the pathogenesis of SLE, involving all 3 complement pathways. Low C3 levels are more strongly correlated with lupus nephritis than low C4 levels, highlighting the significance of the alternative complement pathway in this process.

• #57 Lupus Nephritis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330369-overview

  Autoimmunity plays a major role in the pathogenesis of lupus nephritis. The immunologic mechanisms include production of autoantibodies directed against nuclear elements. Characteristics of the nephritogenic autoantibodies associated with lupus nephritis are as follows: […] These autoantibodies form pathogenic immune complexes intravascularly, which are deposited in glomeruli. Alternatively, autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils. […] The histologic type of lupus nephritis that develops depends on numerous factors, including the antigen specificity and other properties of the autoantibodies and the type of inflammatory response that is determined by other host factors. In more severe forms of lupus nephritis, proliferation of endothelial, mesangial, and epithelial cells and the production of matrix proteins lead to fibrosis.

• #58 Lupus Nephritis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330369-overview

  Autoimmunity plays a major role in the pathogenesis of lupus nephritis. The immunologic mechanisms include production of autoantibodies directed against nuclear elements. Characteristics of the nephritogenic autoantibodies associated with lupus nephritis are as follows: […] These autoantibodies form pathogenic immune complexes intravascularly, which are deposited in glomeruli. Alternatively, autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils. […] The histologic type of lupus nephritis that develops depends on numerous factors, including the antigen specificity and other properties of the autoantibodies and the type of inflammatory response that is determined by other host factors. In more severe forms of lupus nephritis, proliferation of endothelial, mesangial, and epithelial cells and the production of matrix proteins lead to fibrosis.

• #59 Lupus nephritis

  https://www.kidneypathology.com/English_version/Lupus_nephritis.html

  The presence of subendothelial deposits in glomerular capillaries is crucial in the induction of severe damage and they correlate with endocapillary proliferation, necrosis, karyorrhexis and crescents. […] The survival of patients and the preservation of the renal function have improved in the last decades. The treatment is based on corticosteroids and other immunosuppressors. The renal disease is one of the main causes of death in SLE. […] There is hypocomplementemia in most of patients with active disease, and, at least in some, complement levels correlate with the activity of the renal disease. There is a variety of autoantibodies that can be detected in the serum: ANAs, anti-dsDNA, anti-Sm (very specific but few sensible), anti-RNP, anti-Ro, anti-La, anti-histona, and others; anti-DNA antibodies seem important in the pathogenesis of the active lupus nephritis.

• #60 Lupus Nephritis – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/glomerular-disorders/lupus-nephritis

  Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). […] Pathophysiology involves immune complex deposition with development of glomerulonephritis. The immune complexes consist of […] Subendothelial, intramembranous, subepithelial, or mesangial deposits are characteristic. […] Wherever immune complexes are deposited, immunofluorescence staining is positive for complement and for IgG, IgA, and IgM in varying proportions. […] Epithelial cells may proliferate, forming crescents. […] Classification of lupus nephritis is based on histologic findings. […] Activity is estimated by the activity score as well as clinical criteria (eg, urine sediment, increasing urine protein, increasing serum creatinine). […] The activity score describes the degree of inflammation.

• #61 Lupus Nephritis – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/glomerular-disorders/lupus-nephritis

  Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). […] Pathophysiology involves immune complex deposition with development of glomerulonephritis. The immune complexes consist of […] Subendothelial, intramembranous, subepithelial, or mesangial deposits are characteristic. […] Wherever immune complexes are deposited, immunofluorescence staining is positive for complement and for IgG, IgA, and IgM in varying proportions. […] Epithelial cells may proliferate, forming crescents. […] Classification of lupus nephritis is based on histologic findings. […] Activity is estimated by the activity score as well as clinical criteria (eg, urine sediment, increasing urine protein, increasing serum creatinine). […] The activity score describes the degree of inflammation.

• #62 Lupus Nephritis – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/glomerular-disorders/lupus-nephritis

  The chronicity index describes the degree of scarring. […] Treatment for proliferative lupus nephritis combines corticosteroids with other immunosuppressants. […] Induction therapy for focal or diffuse lupus nephritis usually consists of corticosteroids in combination with either mycophenolate or intravenous cyclophosphamide. […] After an appropriate renal response has been achieved with induction therapy, immunosuppressive therapy is continued for at least 2 years and often longer. […] For patients with pure lupus membranous nephropathy, there is a lack of consensus regarding the role of immunosuppressive therapy. […] Kidney transplantation is an option for patients with kidney failure due to lupus nephritis. […] Class of nephritis influences renal prognosis, as do other renal histologic features, baseline kidney function, and race. […] Patients with lupus nephritis are at high risk of cancers, primarily B-cell lymphomas.

• #63 Lupus nephritis: current perspectives and moving forward | JIR

  https://www.dovepress.com/lupus-nephritis-current-perspectives-and-moving-forward-peer-reviewed-fulltext-article-JIR

  For instance, Chung et al described genetic variants in STAT4, ITGAM, K1AA1542, BANK1, and UBE2L3 that are associated with the presence of anti-dsDNA antibodies and may contribute to LN. […] In addition, there is an association of SNP rs7708392 and rs495881 in TNIP1 with LN in a large multi-racial cohort. […] Polymorphisms of APOL1 (apolipoprotein L1 gene) were shown to be significantly associated with the risk of developing end-stage kidney disease due to LN and other nephropathies in individuals of West African descent. […] The identification of new genetic autoimmunity triggers and their validation in animal models is necessary to understand the molecular processes that are essential for the development of LN. […] With an increasing understanding of the pathogenesis of SLE and LN, therapeutics that target single immune elements or signaling pathways might replace conventional unspecific therapeutics such as glucocorticoids or unselective immunosuppressant drugs. […] Inhibition of cytokines or pathways with newly developed biological agents showed positive effects and might inspire future research to develop even more specific, targeted treatments.

• #64 Lupus nephritis, an update | Revista Colombiana de Reumatología (English Edition)

  https://www.elsevier.es/es-revista-revista-colombiana-reumatologia-english-edition–474-articulo-lupus-nephritis-an-update-S2444440523000687

  There is no single way to treat LN; it varies depending on the severity of the disease and the risk of progressive kidney damage, according to the result of the renal biopsy standardized by the ISN/RPS classification of LN. […] Treatment for LN seeks to improve renal function, decrease proteinuria, correct immunological markers, and prevent or reduce cumulative organ damage, in order to achieve complete remission (CR) or partial remission (PR) at 6months, thus avoiding ESRD, dialysis, transplantation and death, and preserving quality of life.

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