Materiały źródłowe

• #1 Granulomatosis with polyangiitis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/granulomatosis-with-polyangiitis/symptoms-causes/syc-20351088

  Granulomatosis with polyangiitis (GPA) is a rare disease that causes swelling, also called inflammation, of small blood vessels. […] The cause of GPA isn’t clear, but the immune system may play a role. […] The exact cause of granulomatosis with polyangiitis (GPA) isn’t clear. The immune system may play a role. Some white blood cells may not function as they should, and they may be involved in the disease. The immune system makes proteins called antibodies that protect the body from germs such as viruses and bacteria. GPA has been linked with the presence of certain antibodies that attack healthy cells by mistake. […] GPA doesn’t spread from person to person. And it likely doesn’t pass from parents to children through genes.

• #2 Granulomatosis With Polyangiitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557827/

  Several complex interactions involving genetics and microbes have been implicated in the etiology of GPA. […] The presumption that ANCAs are responsible for inflammation in GPA is now widely accepted. […] Defective immune-regulatory responses to environmental factors, such as infection or autoantigens, can lead to excessive production of cytokines, which in turn may develop inflammatory granulomatous vascular lesions. […] Understanding the 2 primary types of ANCAs—anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO)—is crucial for comprehending the disease process. […] Some studies suggest that the specific type of ANCA may have better prognostic value compared to the clinical presentation of the disease. […] Genetic associations in GPA include a defective allele for alpha-1 antitrypsin, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), PR3 gene, major histocompatibility complex, class II, DP alpha-1 (HLA-DP) gene, and certain types of FC gamma receptor III b on the surface of neutrophils and macrocytes or monocytes.

• #3 Granulomatosis with Polyangiitis (GPA, formerly Wegener Granulomatosis): Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/332622-overview

  The pathologic hallmarks of GPA are vasculitis of the small- to medium-sized vessels, „geographic” necrosis, and granulomatous inflammation, particularly in the airways. The initial pathologic lesion is that of the granuloma believed to be caused by cellular immune processes. […] Environmental exposures, including respiratory tract infections, have been implicated as inciting factors for granuloma formation. A better understanding of the progression from granuloma to vasculitis may shed light on the possible etiology and pathogenesis of GPA. It is probable that a complex interaction exists between the environment and host factors, many of which are genetically determined. Cellular immune processes are also involved in tissue injury owing to the inflammatory cascade. […] The discovery of ANCAs within neutrophils in the majority of patients with GPA suggested the role of humoral autoimmunity. GPA is usually associated with the presence of diffuse staining cytoplasmic ANCA (C-ANCA) directed against serine proteinase 3 antigen (PR3-ANCA), the so-called Wegener autoantigen.

• #4 Granulomatosis With Polyangiitis (GPA, formerly Wegener’s)

  https://my.clevelandclinic.org/health/diseases/granulomatosis-with-polyangiitis-formerly-wegeners-granulomatosis

  Granulomatosis with polyangiitis (GPA) is an autoimmune disease that can affect your whole body, but especially affects your lungs and kidneys. […] GPA, like other types of vasculitis, is an autoimmune disease. This means your immune system generates ongoing inflammation in your blood vessels. Normally, your immune system sends inflammation to target infections. But in autoimmune diseases, it targets your healthy tissues by mistake. […] Researchers have associated the onset of GPA with certain severe bacterial and viral infections. […] Granulomatosis with polyangiitis (GPA) belongs to a group of conditions called ANCA-associated vasculitis, or AAV. These are types of vasculitis that involve a specific antibody called ANCA. Researchers believe this antibody plays a role in triggering the inflammation in these conditions, including GPA.

• #5 Granulomatosis with Polyangiitis – Vasculitis Foundation

  https://vasculitisfoundation.org/education/vasculitis-types/granulomatosis-with-polyangiitis/

  Granulomatosis with polyangiitis (GPA) is a form of vasculitis, a family of rare disorders characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues. […] The cause of GPA is not yet fully understood. Vasculitis is classified as an autoimmune disorder—a disease that occurs when the body’s natural defense system mistakenly attacks healthy tissue. Abnormal function of white blood cells (neutrophils) is thought to be involved in the disease. […] Researchers believe an infection may contribute to the onset of GPA, but it is unlikely that an infection alone can explain this complex disorder. Environmental and genetic factors may play a role as well. Research is ongoing, but so far, no specific infectious, genetic, or environmental factor has been conclusively associated with GPA.

• #6 Granulomatosis with polyangiitis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/granulomatosis-with-polyangiitis/

  Granulomatosis with polyangiitis (GPA) is a condition that causes inflammation that primarily affects the respiratory tract (including the lungs and airways) and the kidneys. […] The genetic basis of GPA is not well understood. Having a particular version of the HLA-DPB1 gene is the strongest genetic risk factor for developing this condition, although several other genes, some of which have not been identified, may be involved. It is likely that a combination of genetic and environmental factors lead to GPA. […] GPA is an autoimmune disorder. Such disorders occur when the immune system malfunctions and attacks the body’s own tissues and organs. Approximately 90 percent of people with GPA have an abnormal immune protein called an anti-neutrophil cytoplasmic antibody (ANCA) in their blood.

• #7 Granulomatosis with Polyangiitis (GPA, formerly Wegener Granulomatosis): Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/332622-overview

  A pathogenic role for PR3-ANCAs in GPA has been proposed, because PR3-ANCA is strongly associated with the disease; over 90% of GPA patients have been reported to have ANCA positivity during active disease. […] Evidence also comes from in vitro studies. The in vitro effects of PR3-ANCA described to date include activation of primed neutrophils, leading to production of reactive oxygen species, and release of lytic enzymes such as elastase and PR3, which act to promote tissue injury. […] In vivo experimental studies have demonstrated a pathogenic role for MPO-ANCA in mice and rat models. MPO-ANCA induces a pauci-immune necrotizing glomerulonephritis and hemorrhagic capillaritis in these animal models. […] Typically, most autoimmune diseases are attributed to a genetic predisposition combined with exposure to an inciting factor. Genotypic associations in GPA include the following: Carrying a defective allele for alpha-1 antitrypsin; Possessing certain polymorphisms of CTLA-4 (cytotoxic T-lymphocyte antigen 4), which is involved in T-cell activation; Possessing the PTPN22*620W allele, which is typically associated with a positive ANCA status and is also associated with T-cell activation; Carrying the DPB1*0401 allele, which is also associated with chronic beryllium disease, a granulomatous disease; Exhibiting certain forms of the Fc receptor IIIb on the surface of neutrophils and monocytes/macrophages.

• #8 Granulomatosis with Polyangiitis (GPA) – Johns Hopkins Vasculitis Center

  https://www.hopkinsvasculitis.org/types-vasculitis/granulomatosis-with-polyangiitis/

  ANCAs may be not only markers for Granulomatosis with Polyangiitis and related disorders, but they may also be actors in pathogenesis. Studies show that when neutrophils are exposed to cytokines such as tumor necrosis factor, small amounts of serine proteinase and myeloperoxidase, the targets for ANCAs, are expressed on the surface of neutrophils. […] The diagnosis of Granulomatosis with Polyangiitis is established most securely by biopsy specimens showing the triad of vasculitis, granulomata, and large areas of necrosis (known as geographic necrosis) admixed with acute and chronic inflammatory cells. […] Untreated Granulomatosis with Polyangiitis is fatal.

• #9 Granulomatosis with Polyangiitis (GPA) – Vasculitis UK

  https://www.vasculitis.org.uk/about-vasculitis/gpa-granulomatosis-with-polyangiitis

  The cause of GPA is not yet known. Some research suggests that GPA may be triggered by exposure to silica or to infection with staphylococcus aureus bacteria though this is not proven. […] The ANCA antibodies found in most patients with GPA play a role in causing the inflammation of the blood vessels by activating some types of white blood cell. The ANCA antibodies attach to the neutrophils in the blood causing activation. This makes the neutrophil attach to the blood vessel wall and cause damage by release of the chemicals that it usually uses to fight infection. It is not understood why patients develop ANCA antibodies.

• #10 Granulomatosis with polyangiitis – Wikipedia

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

  Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis (WG), is a rare, long-term, systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is an autoimmune disease and a form of vasculitis that affects small- and medium-sized vessels in many organs, but most commonly affects the upper respiratory tract, lungs, and kidneys. […] The cause of GPA is unknown. Genetics have a role in GPA, though the risk of inheritance appears to be low. […] The cause of GPA is unknown, although microbes, such as bacteria and viruses, as well as genetics, have been implicated in its pathogenesis. […] Bacterial colonization with Staphylococcus aureus has been hypothesized as an initiating factor of the autoimmunity seen in people with GPA. […] Several genes involved in the immune system including PTPN22, CTLA4, and human leukocyte antigen genes may influence the risk of developing GPA. […] Antineutrophil cytoplasmic antibodies (ANCAs) now are widely presumed to be responsible for the inflammation in GPA.

• #11 Orphanet: Granulomatosis with polyangiitis

  https://www.orpha.net/en/disease/detail/900

  The pathogenesis of GPA is still under study. Genetic susceptibility factors, environmental agents, infectious episodes and anomalies in innate and adaptive immunity seem to play a role in the development of all ANCA-associated vasculitides. […] Genetic variants appear to correlate with antineutrophil cytoplasmic antibody (ANCA) antigen specificity rather than with clinical phenotype. Thus, cytoplasmic-ANCAs directed to proteinase 3 (PR3-ANCA), found in 60-80% of GPA cases, are associated with genetic variants in HLA-DP1A and HLA-DP1B (6p21.32) which encode a class II major histocompatibility complex, SERPINA1 (14q32.13) encoding alpha-1 antitrypsin, and PRTN3 (19p13.3) encoding the autoantigen proteinase 3.

• #12 Granulomatosis with polyangiitis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/granulomatosis-with-polyangiitis/

  Because the HLA-DPB1 gene is involved in the immune system, changes in it might be related to the autoimmune response and inflammation in the respiratory tract and kidneys characteristic of GPA. However, it is unclear what specific role the HLA-DPB1*0401 gene variant plays in development of this condition.

• #13 Granulomatosis with Polyangiitis (GPA, formerly Wegener Granulomatosis): Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/332622-overview

  The role of microbes in the pathogenesis of AAV has also been explored, although the mechanism has not been fully explained. The first evidence for this was discovered by Stegeman et al, who noted that nasal carriage of Staphylococcus aureus is associated with relapses of GPA (relative risk, 9.0) and prophylactic treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the likelihood of relapse by 60%. […] Living in northern latitudes, farming, drug and environmental allergies, and exposures to solvents or silica have all been linked to the development of GPA.

• #14 Granulomatosis with Polyangiitis (GPA) – Johns Hopkins Vasculitis Center

  https://www.hopkinsvasculitis.org/types-vasculitis/granulomatosis-with-polyangiitis/

  Granulomatosis with Polyangiitis is a disease involving granulomatous inflammation, necrosis and vasculitis that most frequently targets the upper respiratory tract, lower respiratory tract, and kidneys. […] The cause of Granulomatosis with Polyangiitis is not known. Compared to diseases with obvious genetic predispositions, genetics appear to play a relatively small role in the etiology of Granulomatosis with Polyangiitis. […] For some time, an infection has been suspected of causing (or at least contributing to) Granulomatosis with Polyangiitis, but no specific infection (bacterial, viral, fungal, or other) has been identified. […] A novel group of autoantibodies, ANCAs, helps support the diagnosis of Granulomatosis with Polyangiitis and related forms of vasculitis and gives insight into the pathogenesis of these diseases.

• #15 Granulomatosis with Polyangiitis (GPA) – EyeWiki

  https://eyewiki.org/Granulomatosis_with_Polyangiitis_(GPA)

  The cause of GPA has not been fully identified. Formation of the granulomas in GPA begins with the formation of neutrophilic microabscesses. While the initial cause is not completely understood, it is thought that autoantibody development to myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3) ANCA is key in the development of GPA. In persistent GPA, humoral immunity, specifically CD4+ T cells produce IL-17 and IL-23 which contribute to organ injury, particularly in the kidneys. Microbes such as S. aureus could also be involved in the disease process via superantigen stimulation of B and T cells. Molecular mimicry by Staphylococcus aureus is thought to lead to the development of PR3-ANCA.

• #16 Granulomatosis with Polyangiitis (GPA) – EyeWiki

  https://eyewiki.org/Granulomatosis_with_Polyangiitis_(GPA)

  Granulomatosis with polyangiitis (GPA), previously known as Wegener Granulomatosis, is an autoimmune disorder characterized by granulomatous necrotizing vasculitis that typically affects small and/or medium sized blood vessels in the orbit, respiratory tract (sinuses, nose, throat, lungs), and kidneys. […] The cause of GPA is unknown, but it is thought to be autoimmune. There may be environmental contributing factors such as dust, exposure to silica, smoke, or chemicals. Certain medications may also contribute to the development of the disease. Hydralazine, phenytoin, sulfasalazine, anti-thyroid medication, and allopurinol have been potentially implicated. […] Of the three ANCA-associated vasculitides, GPA is the most common. The annual incidence is about 810 cases per million and the prevalence of GPA is estimated to be 3 cases per 100,000 people. These numbers vary by continent but GPA is typically more common in colder climates. Men and women are affected equally. Patients are usually whited and in their 40s-50s but GPA can occur in any age or race.

• #17

  https://link.springer.com/article/10.1007/s42399-019-00083-4

  Granulomatosis with polyangiitis (GPA, previously known as Wegeners granulomatosis) is a type of ANCA-associated vasculitis that affects small- to medium-sized vessels. […] Various factors may have an impact on the etiology of GPA which is treated as an autoimmune disease. Genetic factors, infectious agents (like Staphylococcus aureus), environmental factors (like silica, hydrocarbons, fumes, pesticides, and farming) are considered elements for the development of the disease. […] GPA is known as a disease affecting the upper and lower respiratory tracts and kidneys and associated with otorhinolaryngological and renal manifestations. But it does not mean that GPA is limited only to these organs. Vessels, for example, in the heart, skin, eyes, muscles, gastrointestinal tract, and breast may be involved as well. […] Various factors may have an impact on the etiology of GPA which is treated as an autoimmune disease. Genetic factors, infectious agents (like Staphylococcus aureus), environmental factors (like silica, hydrocarbons, fumes, pesticides, and farming) are considered elements for the development of GPA.

• #18 Granulomatosis With Polyangiitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557827/

  Infections: In addition to the initiation and exacerbation of the vasculitic process, infectious agents have also been known to modulate the clinical phenotype of the disease. […] Certain medications can induce ANCA-associated vasculitis, typically manifesting as rapidly progressive glomerulonephritis. […] The etiology of GPA is attributed to ANCA, which causes an immune-mediated vasculitis of small- and medium-sized vessels, primarily affecting the ears, nose, throat, lungs, and kidneys.

• #19 Granulomatosis with polyangiitis Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/granulomatosis-with-polyangiitis

  Granulomatosis with polyangiitis (GPA) is a rare disorder in which blood vessels become inflamed. This leads to damage in major organs of the body. […] In most cases, the exact cause is not known, but it is an autoimmune disorder. Rarely, vasculitis with positive antineutrophil cytoplasmic antibodies (ANCA) has been caused by several drugs including cocaine cut with levamisole, hydralazine, propylthiouracil, and minocycline. […] GPA is most common in middle-aged adults of northern European descent. It is rare in children.

• #20 Granulomatosis with polyangiitis: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000135.htm

  Granulomatosis with polyangiitis (GPA) is a rare disorder in which blood vessels become inflamed. This leads to damage in major organs of the body. It was formerly known as Wegener’s granulomatosis. […] In most cases, the exact cause is not known, but it is an autoimmune disorder. Rarely, vasculitis with positive antineutrophil cytoplasmic antibodies (ANCA) has been caused by several drugs including cocaine cut with levamisole, hydralazine, propylthiouracil, and minocycline. […] GPA is most common in middle-aged adults of northern European descent. It is rare in children. […] There is no known prevention.

• #21 Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11385631/

  Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized by granulomatous inflammation of the respiratory tract and necrotizing vasculitis of small and medium vessels often associated with the production of anti-neutrophil cytoplasmic antibodies (ANCA) directed mainly against leukocyte proteinase 3 (PR3). […] The pathogenesis of GPA is complex and multifactorial, with ANCA, neutrophils, B and T lymphocytes, monocytes, endothelial cells, and the alternative complement pathway playing important roles. […] Interestingly, there are reports that GPA may arise from a similar genetic predisposition as rheumatoid arthritis (RA). […] Therefore, a rare case of two family members with GPA highlights the potential genetic underpinnings of this disease. […] The combination of ANCA type with clinical phenotype identifies additional subtypes with unique features.

• #22 Granulomatosis with polyangiitis (Wegener’s) (GPA) | Vasculitis Clinical Research Consortium

  https://vcrc.rarediseasesnetwork.org/diseases-studied/granulomatosis-polyangiitis

  Granulomatosis with polyangiitis (Wegener’s) (GPA) is thought to be an auto-immune disease for which there is no known cause. […] Granulomatosis with polyangiitis (Wegener’s) (GPA) is a rare form of vasculitis mainly involving small and medium-sized blood vessels. […] Granulomatosis with polyangiitis (Wegener’s) (GPA) occurs in both men and women and can affect children and adults. […] Although Caucasians are affected more often, people all over the world can get GPA.

• #23 Granulomatosis with Polyangiitis (GPA) | STROKE MANUAL

  https://www.stroke-manual.com/granulomatosis-with-polyangiitis-gpa/

  the exact cause of GPA is unknown […] a cellular component and a role of autoantibodies are presumed […] other contributing factors include: genetic factors, infection (as an initiating factor for inflammation), some medications (phenytoin, antithyroid drugs, allopurinol) […] ANCAs are autoantibodies directed against specific components of neutrophils. ANCAs are associated with several autoimmune diseases ANCA-Associated Vasculitides (AAV) […] granulomatosis with polyangiitis (GPA) proteinase 3 (PR3) ANCAs (C-ANCA); GPA is the most common (estimated incidence of 10-20 cases per million; peak incidence at 64-75 years of age) […] perinuclear-ANCA (p-ANCA or MPO-ANCA) is directed against myeloperoxidase; p-ANCA is typical for MPA.

• #24 Granulomatosis with Polyangiitis (GPA) – Musculoskeletal and Connective Tissue Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/vasculitis/granulomatosis-with-polyangiitis-gpa

  A positive ANCA test does not exclude mycobacterial and fungal infections; thus, patients with positive ANCA results and cavitary lung lesions still require bronchoscopy and adequate cultures and other tests for tuberculosis and fungal infections. […] Biopsy should be done if possible to confirm the diagnosis of GPA. Clinically abnormal sites may be biopsied first. Biopsy of affected lung tissue is most likely to reveal characteristic findings; open thoracotomy provides the best access. […] Prognosis depends on the severity and extent of disease and at least as much on how rapidly treatment occurs. […] Use of immunosuppressants for severe disease has dramatically improved prognosis.

• #25 Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11385631/

  Several studies have shown that MPO-ANCA positive GPA patients have more frequently limited disease, and a high prevalence of SGS, as well as fewer constitutional symptoms and milder renal lesion at diagnosis compared with those tested as PR3-ANCA positive. […] However, in the recent study, within the GPA group (N=151, 29% MPO+) patients with MPO-ANCA were older, and characterized by less prevalent ENT and neurological manifestations, increased end-stage renal disease (ESRD) and mortality.

• #26 AB0471 Granulomatosis with polyangiitis (gpa, wegener’s): complications and causes of death | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/72/Suppl_3/A933.2

  Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis with predominant involvement of the upper airways, pulmonary parenchyma and kidneys. […] Combined pulmonary and renal failure holds leading position among causes of death in patients with GPA (observed in six cases (54,5%). […] Common cause of death from GPA was profuse hemorrhage from the eroded vessels of the upper respiratory tract, lungs and intestine. […] The complications and causes of death in patients with GPA are: combined pulmonary and renal failure; profuse hemorrhage from the eroded vessels of the upper respiratory tract, lungs, intestine; infectious complications; central nervous system disorders.

• #27 Granulomatosis with polyangiitis | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/granulomatosis-polyangiitis/

  As with most types of vasculitis, we do not know exactly what causes the disease to develop. […] The treatment is with steroids and an immunosuppressant drug, usually cyclophosphamide or mycophenolate mofetil which dampens down the body’s immune system. […] The key to a good outcome is early diagnosis, but GPA is still a serious disease with a small risk of death in some patients.

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