Materiały źródłowe

• #1 Juvenile Arthritis Treatment & Diagnosis | NIAMS

  https://www.niams.nih.gov/health-topics/juvenile-arthritis

  JIA is idiopathic, meaning that its origins are not understood. While the exact causes of JIA are unknown, it begins when the immune system becomes overactive and creates inflammation. […] Scientists do not know why the immune system attacks healthy tissues in children with JIA, but they believe that a complex mix of genes and environmental factors are involved. […] While the origin of the immune systems overreaction in JIA is unknown, scientists have identified some of the molecules that contribute to inflammation in some forms of the disease, including TNF-alpha, IL-6, and IL-1. This has led to new therapies that specifically target these molecules.

• #1 Juvenile Idiopathic Arthritis (JIA) Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/10370-juvenile-idiopathic-arthritis

  Juvenile idiopathic arthritis (JIA) is an autoimmune disease in which your child’s immune system mistakenly targets the synovium (the tissue that lines the inside of the joint) and the synovial fluid in the joint. This causes the synovium to make extra fluid, which leads to swelling, pain and joint stiffness. […] Experts don’t yet know what causes JIA. In fact, the term idiopathic means unknown cause. Possible contributing factors may include: Environmental factors that influence your child’s immune system, Genetics, Infection.

• #1 Juvenile idiopathic arthritis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/juvenile-idiopathic-arthritis/

  Juvenile idiopathic arthritis is thought to arise from a combination of genetic and environmental factors. The term „idiopathic” indicates that the specific cause of the disorder is unknown. Its signs and symptoms result from excessive inflammation in and around the joints. […] Researchers have identified changes in several genes that may influence the risk of developing juvenile idiopathic arthritis. Some of these genes belong to a family of genes that provide instructions for making a group of related proteins called the human leukocyte antigen (HLA) complex. […] Normal variations in several other genes have also been associated with juvenile idiopathic arthritis. Many of these genes are thought to play roles in immune system function. […] Additional unknown genetic influences and environmental factors, such as infection and other issues that affect immune health, are also likely to influence a person’s chances of developing this complex disorder.

• #1 Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches | Pediatric Rheumatology | Full Text

  https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-021-00629-8

  Several studies have documented genetic associations to JIA. Genetic linkage depends on subtype and may be divided into two groups: HLA genes and non-HLA-related genes. […] The main gene associated with ERA is HLA-B27, with other genes predisposing the development of ERA being DRB1*01, DQA1*01, and DQB1*05. […] Genetic pre-disposition of non-HLA-related genes plays a pivotal role in the onset of inflammatory response leading to tissue damage. […] The pathogenesis of ERA is driven by HLA-B27-mediated presentation of arthritogenic peptide following T-cell activation and IL23 and IL17 secretion. […] In sJIA, uncontrolled activation of the innate immune system results in activation of monocytes/macrophages, neutrophils and immature (CD34+CD33+) myelomonocytic precursors, and increased production of pro-inflammatory cytokines IL1, IL6, IL18 and phagocyte-specific S100 proteins.

• #1 Juvenile Idiopathic Arthritis | Phoenix Children’s Hospital

  https://phoenixchildrens.org/specialties-conditions/juvenile-idiopathic-arthritis

  Juvenile idiopathic arthritis (JIA) is a form of arthritis in children. […] JIA may be caused by several things. These include genes and the environment. The disease can run in families, but it can also be set off by exposure to certain things. JIA is linked to part of a gene called HLA antigen DR4. A person with this antigen may be more likely to have the disease.

• #1 Juvenile Idiopathic Arthritis: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/1007276-overview

  The etiology is unknown, and the genetic component is complex, making clear distinctions between the various subtypes difficult. […] The etiology and pathogenesis of JIA are not completely understood. Genetic susceptibility plays a major role, but there is significant overlap between loci associated with JIA and those associated with other autoimmune diseases. […] JIA is a genetically complex disorder in which multiple genes are important for disease onset and manifestations. The IL2RA/CD25 gene has been implicated as a JIA susceptibility locus, as has the VTCN1 gene. […] Associations have been found between specific HLA alleles and clinical subtypes of JIA (eg, HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, and HLA-DRB1(*)04:05 with polyarticular JIA, in a Japanese cohort).

• #1 What is juvenile arthritis? Common symptoms, causes, and treatments

  https://www.singlecare.com/blog/juvenile-arthritis/

  Juvenile idiopathic arthritis (JIA), affecting nearly 300,000 children in the U.S., is an autoimmune disease where the immune system mistakenly attacks the joints, with causes believed to be genetic, infectious, or environmental. […] There is no definitive known cause for the condition but there are hypotheses suggesting genetic, infectious and environmental factors may be involved, says Magdalena Cadet, MD, a New Yorkbased rheumatologist and associate attending at NYU Langone Medical Center. […] Only a small percentage of juvenile idiopathic arthritis cases have been reported to run in families, but a sibling of someone with the condition has about 12 times an estimated risk of developing juvenile arthritis than that of the general population.

• #1 The Etiology of Juvenile Idiopathic Arthritis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/25384710/

  Over the years, the commonly used term to describe juvenile idiopathic arthritis (JIA) has changed. […] JIA pathogenesis is still poorly understood: the interaction between environmental factors and multiple genes has been proposed as the most relevant working mechanism to the development of JIA. […] JIA development might be initiated and sustained by the exposure to environmental factors, including infectious agents which affect people at a young age, depending on the underlying genetic predisposition to synovial inflammation. […] Many data from patients with JIA suggest a scenario in which different external antigens incite multiple antigen-specific pathways, cytotoxic T cell responses, activation of classical complement cascade, and production of proinflammatory cytokines. […] No unequivocal evidence favoring or refuting these associations has been clearly proved, and today, the strict definition of JIA etiology remains unknown. […] The infection can represent a random event in a susceptible individual, or it can be a necessary factor in JIA development, always in combination with a peculiar genetic background.

• #1 Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches | Pediatric Rheumatology | Full Text

  https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-021-00629-8

  Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. […] The heterogeneity of JIA disease subtypes adds complexity to the investigation of cause and mechanism of pathogenesis, and the initiating factors of JIA remain unresolved. […] Environmental factors, including infectious agents, vaccinations, antibiotics, vitamin D deficiency, stress and trauma have been proposed as risk factors. Infectious viruses (Epstein-Barr virus, Parvovirus B, Rubivirus, Hepatitis B virus) and bacteria (Salmonella spp., Shigella spp., Campylobacter spp., S. pyogenes, B. henselae, M. pneumoniae, Chlamydophila pneumonia) have been reported as causal factors provoking JIA.

• #1 Juvenile Idiopathic Arthritis: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/1007276-overview

  Some pediatric rheumatologists view systemic-onset JIA as an autoinflammatory disorder, such as familial Mediterranean fever (FMF) or cryopyrin-associated periodic fever syndromes, rather than a subtype of JIA. […] A study by Ayaz et al found an increased frequency of MEFV mutations in Turkish children who were diagnosed with systemic JIA; this study has not been replicated in other populations. […] In a nested casecontrol study of 153 children with juvenile arthritis and 1,530 matched controls, researchers found that exposure to antibiotics during childhood significantly increased the risk for developing JIA (adjusted odds ratio = 2.6) in a dose-dependent manner.

• #1 Juvenile idiopathic arthritis

  https://dermnetnz.org/topics/juvenile-idiopathic-arthritis

  JIA is recognised as having seven major subtypes, some of which exhibit the clinical and pathological features of other autoimmune disorders; these subtypes include: […] The exact cause of JIA is unclear, but a pronounced immune response in a perpetuating loop of both innate and adaptive immunity is believed to contribute to the pathogenesis of JIA. Aberrant activation of the innate immune system lead to the dysregulated production of proinflammatory cytokines. Tumour necrosis factor alpha (TNF-), interleukin (IL)-1, and IL-6 play a critical inciting role. […] Environmental factors may contribute to the development of JIA. Some studies have suggested associations with exposure to antibiotics, a bacterial infection in immunosuppressed individuals, and maternal smoking during pregnancy. […] Some studies have consistently supported associations between enthesitis-related JIA and human leukocyte antigen (HLA) polymorphisms; there appear to be increased associations, especially with early-onset disease. A monogenic form of systemic JIA with an underlying mutation in a regulatory protein involved in macrophage metabolism has been described.

• #1 Juvenile Idiopathic Arthritis (JIA) | Arthritis Foundation

  https://www.arthritis.org/diseases/juvenile-idiopathic-arthritis

  Juvenile idiopathic arthritis (JIA) is the most common type of arthritis in kids and teens. […] JIA types are autoimmune or autoinflammatory diseases. […] The word idiopathic means unknown, and researchers aren’t sure why kids develop JIA. They believe kids with JIA have certain genes that are activated by a virus, bacteria or other external factors. […] But there is no evidence that foods, toxins, allergies or lack of vitamins cause the disease.

• #1 Juvenile Idiopathic Arthritis: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/1007276-overview

  A study by Ombrello examined the MHC locus in a large collection of systemic juvenile idiopathic arthritis patients and verified the relationship between the class II HLA region and systemic juvenile idiopathic arthritis, implicating adaptive immune molecules in the pathogenesis of the disease. […] Humoral and cell-mediated immunity are involved in the pathogenesis of JIA. T lymphocytes have a central role, releasing proinflammatory cytokines (eg, tumor necrosis factoralpha [TNF-], interleukin [IL]-6, IL-1) and favoring a type-1 helper T-lymphocyte response. […] A disordered interaction between type 1 and type 2 T-helper cells has been postulated. […] Evidence for abnormalities in the humoral immune system include the increased presence of autoantibodies (especially antinuclear antibodies), increased serum immunoglobulins, the presence of circulating immune complexes, and complement activation.

• #1 Juvenile idiopathic arthritis: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000451.htm

  Juvenile idiopathic arthritis (JIA) is a term used to describe a group of disorders in children that includes arthritis. They are long-term (chronic) diseases that cause joint pain and swelling. The cause of JIA is not known. It is thought to be an autoimmune illness. This means the body attacks and destroys healthy body tissue by mistake. […] The International League of Associations for Rheumatology (ILAR) has proposed the following way of grouping this type of childhood arthritis: […] There is no known prevention for JIA.

• #1 Systemic Juvenile Idiopathic Arthritis | Arthritis Foundation

  https://www.arthritis.org/diseases/systemic-juvenile-idiopathic-arthritis

  Systemic juvenile idiopathic arthritis (SJIA) is a rare subtype of juvenile idiopathic arthritis that causes body-wide inflammation. […] Exactly what causes SJIA isn’t clear. The general theory is that a child has a genetic predisposition, and the disease onset is triggered by something in the environment. The word idiopathic means the cause or trigger is not known. […] Research suggests that SJIA is different. It may be an autoinflammatory condition that causes the innate immune system to be activated even when there is no infection to fight. Several factors have led researchers to think that SJIA is an autoinflammatory disease. […] For one thing, children with SJIA usually don’t have autoantibodies in their blood, as many kids with other forms of JIA do. […] Also, kids with SJIA have high blood levels of two inflammatory proteins (cytokines) called interleukin-1 (IL-1) and interleukin-6 (IL-6). These proteins are known to cause inflammation in other autoinflammatory diseases and are believed to trigger inflammation in SJIA.

• #1

  https://www.healthychildren.org/English/health-issues/conditions/chronic/Pages/Juvenile-Idiopathic-Arthritis.aspx

  Juvenile idiopathic Arthritis (JIA) is a chronic form of arthritis that affects children and teens. […] What we do know is that in children with JIA, the immune system causes inflammation in joints. What we do not know yet is why. It is likely that multiple factors can contribute to developing JIA. Some children may have been exposed to an illness, a certain medication or something else in their environment that triggers the immune system. […] Some children may be more likely to develop arthritis because of the genes they inherited from their parents. […] It is important to know that there are no labs that diagnose JIA. […] Children with multiple joints involved, those with arthritis that affects the hip, ankle or wrist, or who have joint damage that can be seen on x-rays are likely to have more challenging cases of JIA. […] Children with a specific genetic marker called HLA-B27 are more likely to develop inflammation in their sacroiliac joints, where the base of the spine connects to the hip bones. This can cause stiffness and pain in the lower back.

• #1 Juvenile rheumatoid arthritis: Symptoms, treatment, and prognosis

  https://www.medicalnewstoday.com/articles/325708

  Most doctors now call the condition juvenile idiopathic arthritis, or JIA. A condition is idiopathic when its cause is unknown. While doctors think that JIA is an autoimmune condition, meaning that it happens when the body attacks healthy tissue, they do not know why some children get it. […] Most research suggests that JIA is an autoimmune condition. Autoimmune disorders occur when the immune system initiates an attack on healthy tissue as if it were an infection. In JIA, the immune system attacks the tissue of the joints. […] A combination of genetics and environmental factors may determine who develops JIA. Children with JIA may carry genes that predispose them to the condition, then develop symptoms following a triggering event, such as a virus or injury. […] A 2016 analysis found that children with allergies are more likely to develop JIA. Allergies might somehow trigger the activation of genes for arthritis, or the genes that predispose children to arthritis might be similar to those that cause allergies.

• #1 Juvenile Idiopathic Arthritis (JIA) | Cause, Types & Treatment

  https://www.cincinnatichildrens.org/health/j/jia

  Children with juvenile idiopathic arthritis (JIA) have inflammation of the joints that is called arthritis. […] The exact cause is unknown. JIA is believed to be caused by a combination of genetic and environmental factors. Researchers think that something in the environment impacts or 'triggers’ the immune system, especially in people who have genetic factors that make them more likely to get arthritis. […] Although we still do not understand the exact cause of JIA, we have recently learned a great deal about what is responsible for chronic inflammation. We now know that three molecules called Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6) and Interleukin-1 (IL-1) are the major factors that keep inflammation in the joints active.

• #1 Overview of Juvenile Idiopathic Arthritis

  https://openorthopaedicsjournal.com/VOLUME/14/PAGE/101/FULLTEXT/

  Juvenile Idiopathic Arthritis (JIA) is the most common cause of arthritis in childhood. […] The precise etiology of JIA is unknown, and is likely the result of a complex interaction between genetics and the environment. […] It is hypothesized that an environmental exposure in a genetically susceptible child leads to an altered immune response. […] The genetics of JIA have been extensively studied, and it is likely a polygenic disease. […] Furthermore, multiple studies have described an association between HLA alleles and both oligoarticular and polyarticular JIA. […] Genome-wide association studies have identified multiple single nucleotide polymorphisms that are associated with oligoarticular and RF negative polyarticular JIA, likely uniquely contributing to their pathogenesis. […] A possible theory for an environmental trigger is an infection as heat shock proteins are found to be elevated in JIA patients. […] However, no specific infection has yet been confirmed. Further studies are needed to describe the role of genetics and the environment in the pathogenesis of JIA.

• #1

  https://link.springer.com/article/10.1007/s12016-014-8460-9

  Over the years, the commonly used term to describe juvenile idiopathic arthritis (JIA) has changed. […] JIA pathogenesis is still poorly understood: the interaction between environmental factors and multiple genes has been proposed as the most relevant working mechanism to the development of JIA. […] JIA development might be initiated and sustained by the exposure to environmental factors, including infectious agents which affect people at a young age, depending on the underlying genetic predisposition to synovial inflammation. […] Many data from patients with JIA suggest a scenario in which different external antigens incite multiple antigen-specific pathways, cytotoxic T cell responses, activation of classical complement cascade, and production of proinflammatory cytokines. […] No unequivocal evidence favoring or refuting these associations has been clearly proved, and today, the strict definition of JIA etiology remains unknown. […] The infection can represent a random event in a susceptible individual, or it can be a necessary factor in JIA development, always in combination with a peculiar genetic background. […] Further studies are needed in order to address the unsolved questions concerning this issue.

• #1 Juvenile Idiopathic Arthritis

  https://www.printo.it/pediatric-rheumatology/IE/info/2/Juvenile-Idiopathic-Arthritis

  The prognosis of arthritis has improved significantly over the years, but still depends on the severity and type of JIA and early and appropriate treatment. There is ongoing research to develop new drugs and biologic agents and also to make treatment available to all children. Arthritis prognosis has considerably improved in the last ten years. Overall, around 40% of children will be off medication and without symptoms (remission) 8-10 years from disease onset; the highest rates of remission are in the oligoarticular persistent and systemic types.

• #2 Juvenile Idiopathic Arthritis (JIA) Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/10370-juvenile-idiopathic-arthritis

  Juvenile idiopathic arthritis (JIA) is an autoimmune disease in which your child’s immune system mistakenly targets the synovium (the tissue that lines the inside of the joint) and the synovial fluid in the joint. This causes the synovium to make extra fluid, which leads to swelling, pain and joint stiffness. […] Experts don’t yet know what causes JIA. In fact, the term idiopathic means unknown cause. Possible contributing factors may include: Environmental factors that influence your child’s immune system, Genetics, Infection.

• #2 Juvenile Idiopathic Arthritis (JIA) | Arthritis Foundation

  https://www.arthritis.org/diseases/juvenile-idiopathic-arthritis

  Juvenile idiopathic arthritis (JIA) is the most common type of arthritis in kids and teens. […] JIA types are autoimmune or autoinflammatory diseases. […] The word idiopathic means unknown, and researchers aren’t sure why kids develop JIA. They believe kids with JIA have certain genes that are activated by a virus, bacteria or other external factors. […] But there is no evidence that foods, toxins, allergies or lack of vitamins cause the disease.

• #2 Juvenile Idiopathic Arthritis: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/1007276-overview

  The etiology is unknown, and the genetic component is complex, making clear distinctions between the various subtypes difficult. […] The etiology and pathogenesis of JIA are not completely understood. Genetic susceptibility plays a major role, but there is significant overlap between loci associated with JIA and those associated with other autoimmune diseases. […] JIA is a genetically complex disorder in which multiple genes are important for disease onset and manifestations. The IL2RA/CD25 gene has been implicated as a JIA susceptibility locus, as has the VTCN1 gene. […] Associations have been found between specific HLA alleles and clinical subtypes of JIA (eg, HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, and HLA-DRB1(*)04:05 with polyarticular JIA, in a Japanese cohort).

• #2 Juvenile Idiopathic Arthritis | HSS Pediatric Rheumatology

  https://www.hss.edu/conditions_juvenile-idiopathic-arthritis.asp

  „Idiopathic” means „unknown cause,” and the exact cause of JIA is not known, though there is a lot of research being done on this subject. All types of JIA are thought to be due to a combination of genetic and environmental factors. […] Certain genetic markers, such as HLA-B27, are also associated with JIA. Some children have JIA with no positive antibodies or genetic markers.

• #2

  https://www.healthychildren.org/English/health-issues/conditions/chronic/Pages/Juvenile-Idiopathic-Arthritis.aspx

  Juvenile idiopathic Arthritis (JIA) is a chronic form of arthritis that affects children and teens. […] What we do know is that in children with JIA, the immune system causes inflammation in joints. What we do not know yet is why. It is likely that multiple factors can contribute to developing JIA. Some children may have been exposed to an illness, a certain medication or something else in their environment that triggers the immune system. […] Some children may be more likely to develop arthritis because of the genes they inherited from their parents. […] It is important to know that there are no labs that diagnose JIA. […] Children with multiple joints involved, those with arthritis that affects the hip, ankle or wrist, or who have joint damage that can be seen on x-rays are likely to have more challenging cases of JIA. […] Children with a specific genetic marker called HLA-B27 are more likely to develop inflammation in their sacroiliac joints, where the base of the spine connects to the hip bones. This can cause stiffness and pain in the lower back.

• #2 Juvenile Idiopathic Arthritis

  https://www.nationwidechildrens.org/conditions/health-library/juvenile-idiopathic-arthritis

  JIA is an autoimmune disease. This means the body’s immune system attacks its own healthy cells and tissues. JIA may be caused by several things. These include genes and the environment. The disease can run in families, but it can also be set off by exposure to certain things. JIA is linked to part of a gene called HLA antigen DR4. A person with this antigen may be more likely to have the disease. […] Like adult rheumatoid arthritis, JIA is an autoimmune disease. This means the body’s immune system attacks its own healthy cells and tissues. JIA may be caused by several things. These include genes and the environment. The disease can run in families, but it can also be set off by exposure to certain things. JIA is linked to part of a gene called HLA antigen DR4. A person with this antigen may be more likely to have the disease.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Symptoms-and-Causes-of-Juvenile-Idiopathic-Arthritis.aspx

  Juvenile idiopathic arthritis is an autoimmune condition. The synovial membrane that lines the affected joint is eaten away by inflammatory injury caused by antibodies directed against the bodys own antigens (autoantibodies). […] Juvenile idiopathic arthritis is due to a combination of genetic and environmental factors. Some variations in certain genes associated with the immune reaction of the individual, called the HLA complex, are known to be linked to a higher incidence of the disease. Infection, inflammation, and disease are also thought to precipitate the disorder in predisposed individuals. […] Few people with JIA report a family history of the disease, but the risk of developing JIA is 12 times higher for siblings of an affected person compared to the general population.

• #2 Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches | Pediatric Rheumatology | Full Text

  https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-021-00629-8

  Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. […] The heterogeneity of JIA disease subtypes adds complexity to the investigation of cause and mechanism of pathogenesis, and the initiating factors of JIA remain unresolved. […] Environmental factors, including infectious agents, vaccinations, antibiotics, vitamin D deficiency, stress and trauma have been proposed as risk factors. Infectious viruses (Epstein-Barr virus, Parvovirus B, Rubivirus, Hepatitis B virus) and bacteria (Salmonella spp., Shigella spp., Campylobacter spp., S. pyogenes, B. henselae, M. pneumoniae, Chlamydophila pneumonia) have been reported as causal factors provoking JIA.

• #2 The Etiology of Juvenile Idiopathic Arthritis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/25384710/

  Over the years, the commonly used term to describe juvenile idiopathic arthritis (JIA) has changed. […] JIA pathogenesis is still poorly understood: the interaction between environmental factors and multiple genes has been proposed as the most relevant working mechanism to the development of JIA. […] JIA development might be initiated and sustained by the exposure to environmental factors, including infectious agents which affect people at a young age, depending on the underlying genetic predisposition to synovial inflammation. […] Many data from patients with JIA suggest a scenario in which different external antigens incite multiple antigen-specific pathways, cytotoxic T cell responses, activation of classical complement cascade, and production of proinflammatory cytokines. […] No unequivocal evidence favoring or refuting these associations has been clearly proved, and today, the strict definition of JIA etiology remains unknown. […] The infection can represent a random event in a susceptible individual, or it can be a necessary factor in JIA development, always in combination with a peculiar genetic background.

• #2 Juvenile idiopathic arthritis

  https://dermnetnz.org/topics/juvenile-idiopathic-arthritis

  JIA is recognised as having seven major subtypes, some of which exhibit the clinical and pathological features of other autoimmune disorders; these subtypes include: […] The exact cause of JIA is unclear, but a pronounced immune response in a perpetuating loop of both innate and adaptive immunity is believed to contribute to the pathogenesis of JIA. Aberrant activation of the innate immune system lead to the dysregulated production of proinflammatory cytokines. Tumour necrosis factor alpha (TNF-), interleukin (IL)-1, and IL-6 play a critical inciting role. […] Environmental factors may contribute to the development of JIA. Some studies have suggested associations with exposure to antibiotics, a bacterial infection in immunosuppressed individuals, and maternal smoking during pregnancy. […] Some studies have consistently supported associations between enthesitis-related JIA and human leukocyte antigen (HLA) polymorphisms; there appear to be increased associations, especially with early-onset disease. A monogenic form of systemic JIA with an underlying mutation in a regulatory protein involved in macrophage metabolism has been described.

• #2 For parents

  https://www.rch.org.au/rheumatology/information_about_rheumatological_conditions/For_Parents/

  This information sheet is about Juvenile Idiopathic Arthritis (JIA), its cause, treatment and what it may mean for your child and your family. […] We do not know the causes of JIA. However, we do know it is an auto-immune condition. Our bodies have an immune system which fights germs or viruses to keep us healthy. Sometimes the body’s immune system mistakes a normal part of the body for something foreign (like a germ), and starts attacking the body itself. In JIA the immune system attacks the joints. This is called an auto-immune process. We don’t understand precisely how, or why this happens. […] JIA is not hereditary – it is not passed on from parent to child. It is rare for two children in the same family to have JIA, although this can happen. Genes do play a role, but are only one of a number of factors necessary to develop JIA. […] There are myths that JIA is caused by being too cold, by living in a cold climate or eating particular foods. None of these actually contribute to a child getting JIA.

• #2 Juvenile Idiopathic Arthritis (JIA) | Cause, Types & Treatment

  https://www.cincinnatichildrens.org/health/j/jia

  Children with juvenile idiopathic arthritis (JIA) have inflammation of the joints that is called arthritis. […] The exact cause is unknown. JIA is believed to be caused by a combination of genetic and environmental factors. Researchers think that something in the environment impacts or 'triggers’ the immune system, especially in people who have genetic factors that make them more likely to get arthritis. […] Although we still do not understand the exact cause of JIA, we have recently learned a great deal about what is responsible for chronic inflammation. We now know that three molecules called Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6) and Interleukin-1 (IL-1) are the major factors that keep inflammation in the joints active.

• #2 Systemic Juvenile Idiopathic Arthritis | Arthritis Foundation

  https://www.arthritis.org/diseases/systemic-juvenile-idiopathic-arthritis

  Systemic juvenile idiopathic arthritis (SJIA) is a rare subtype of juvenile idiopathic arthritis that causes body-wide inflammation. […] Exactly what causes SJIA isn’t clear. The general theory is that a child has a genetic predisposition, and the disease onset is triggered by something in the environment. The word idiopathic means the cause or trigger is not known. […] Research suggests that SJIA is different. It may be an autoinflammatory condition that causes the innate immune system to be activated even when there is no infection to fight. Several factors have led researchers to think that SJIA is an autoinflammatory disease. […] For one thing, children with SJIA usually don’t have autoantibodies in their blood, as many kids with other forms of JIA do. […] Also, kids with SJIA have high blood levels of two inflammatory proteins (cytokines) called interleukin-1 (IL-1) and interleukin-6 (IL-6). These proteins are known to cause inflammation in other autoinflammatory diseases and are believed to trigger inflammation in SJIA.

• #2 Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches | Pediatric Rheumatology | Full Text

  https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-021-00629-8

  Several studies have documented genetic associations to JIA. Genetic linkage depends on subtype and may be divided into two groups: HLA genes and non-HLA-related genes. […] The main gene associated with ERA is HLA-B27, with other genes predisposing the development of ERA being DRB1*01, DQA1*01, and DQB1*05. […] Genetic pre-disposition of non-HLA-related genes plays a pivotal role in the onset of inflammatory response leading to tissue damage. […] The pathogenesis of ERA is driven by HLA-B27-mediated presentation of arthritogenic peptide following T-cell activation and IL23 and IL17 secretion. […] In sJIA, uncontrolled activation of the innate immune system results in activation of monocytes/macrophages, neutrophils and immature (CD34+CD33+) myelomonocytic precursors, and increased production of pro-inflammatory cytokines IL1, IL6, IL18 and phagocyte-specific S100 proteins.

• #2 Juvenile Rheumatoid Arthritis (JRA) Basics: RA In Children

  https://www.webmd.com/rheumatoid-arthritis/understanding-juvenile-rheumatoid-arthritis-basics

  Juvenile rheumatoid arthritis (JRA), often referred to by doctors today as juvenile idiopathic arthritis (JIA), is a type of arthritis that causes joint inflammation and stiffness for more than six weeks in a child aged 16 or younger. […] JRA is an autoimmune disorder, which means that the body mistakenly identifies some of its own cells and tissues as foreign. […] Researchers still don’t know exactly why the immune system goes awry in children who develop JRA, although they suspect that it’s a two-step process. First, something in a child’s genetic makeup gives them a tendency to develop Juvenile rheumatoid (JRA). Then an environmental factor, such as a virus, triggers the development of JRA. […] The main difference between juvenile and adult arthritis is that some children with JRA outgrow the illness, while adults usually have lifelong symptoms. […] Additionally, unlike adult rheumatoid arthritis, JRA may affect bone development as well as the child’s growth.

• #2

  https://link.springer.com/article/10.1007/s12016-014-8460-9

  Over the years, the commonly used term to describe juvenile idiopathic arthritis (JIA) has changed. […] JIA pathogenesis is still poorly understood: the interaction between environmental factors and multiple genes has been proposed as the most relevant working mechanism to the development of JIA. […] JIA development might be initiated and sustained by the exposure to environmental factors, including infectious agents which affect people at a young age, depending on the underlying genetic predisposition to synovial inflammation. […] Many data from patients with JIA suggest a scenario in which different external antigens incite multiple antigen-specific pathways, cytotoxic T cell responses, activation of classical complement cascade, and production of proinflammatory cytokines. […] No unequivocal evidence favoring or refuting these associations has been clearly proved, and today, the strict definition of JIA etiology remains unknown. […] The infection can represent a random event in a susceptible individual, or it can be a necessary factor in JIA development, always in combination with a peculiar genetic background. […] Further studies are needed in order to address the unsolved questions concerning this issue.

• #2 Juvenile Arthritis Treatment & Diagnosis | NIAMS

  https://www.niams.nih.gov/health-topics/juvenile-arthritis

  JIA is idiopathic, meaning that its origins are not understood. While the exact causes of JIA are unknown, it begins when the immune system becomes overactive and creates inflammation. […] Scientists do not know why the immune system attacks healthy tissues in children with JIA, but they believe that a complex mix of genes and environmental factors are involved. […] While the origin of the immune systems overreaction in JIA is unknown, scientists have identified some of the molecules that contribute to inflammation in some forms of the disease, including TNF-alpha, IL-6, and IL-1. This has led to new therapies that specifically target these molecules.

• #2 Juvenile Idiopathic Arthritis: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/1007276-overview

  A study by Ombrello examined the MHC locus in a large collection of systemic juvenile idiopathic arthritis patients and verified the relationship between the class II HLA region and systemic juvenile idiopathic arthritis, implicating adaptive immune molecules in the pathogenesis of the disease. […] Humoral and cell-mediated immunity are involved in the pathogenesis of JIA. T lymphocytes have a central role, releasing proinflammatory cytokines (eg, tumor necrosis factoralpha [TNF-], interleukin [IL]-6, IL-1) and favoring a type-1 helper T-lymphocyte response. […] A disordered interaction between type 1 and type 2 T-helper cells has been postulated. […] Evidence for abnormalities in the humoral immune system include the increased presence of autoantibodies (especially antinuclear antibodies), increased serum immunoglobulins, the presence of circulating immune complexes, and complement activation.

• #2 Juvenile idiopathic arthritis (JIA) | Symptoms, treatments

  https://versusarthritis.org/about-arthritis/conditions/juvenile-idiopathic-arthritis/

  Juvenile idiopathic arthritis (JIA) is an autoimmune disease. […] We don’t completely understand what causes JIA. In fact, that’s what idiopathic means. […] JIA is thought to be due to a combination of genetic factors and trigger factors from the environment, for example the infections that your immune system has been in touch with. […] There’s no evidence that a specific infection causes JIA, but an infection may trigger your immune system’s response that then carries on and affects your joints.

• #2 Overview of Juvenile Idiopathic Arthritis

  https://openorthopaedicsjournal.com/VOLUME/14/PAGE/101/FULLTEXT/

  Juvenile Idiopathic Arthritis (JIA) is the most common cause of arthritis in childhood. […] The precise etiology of JIA is unknown, and is likely the result of a complex interaction between genetics and the environment. […] It is hypothesized that an environmental exposure in a genetically susceptible child leads to an altered immune response. […] The genetics of JIA have been extensively studied, and it is likely a polygenic disease. […] Furthermore, multiple studies have described an association between HLA alleles and both oligoarticular and polyarticular JIA. […] Genome-wide association studies have identified multiple single nucleotide polymorphisms that are associated with oligoarticular and RF negative polyarticular JIA, likely uniquely contributing to their pathogenesis. […] A possible theory for an environmental trigger is an infection as heat shock proteins are found to be elevated in JIA patients. […] However, no specific infection has yet been confirmed. Further studies are needed to describe the role of genetics and the environment in the pathogenesis of JIA.

• #3 The Etiology of Juvenile Idiopathic Arthritis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/25384710/

  Over the years, the commonly used term to describe juvenile idiopathic arthritis (JIA) has changed. […] JIA pathogenesis is still poorly understood: the interaction between environmental factors and multiple genes has been proposed as the most relevant working mechanism to the development of JIA. […] JIA development might be initiated and sustained by the exposure to environmental factors, including infectious agents which affect people at a young age, depending on the underlying genetic predisposition to synovial inflammation. […] Many data from patients with JIA suggest a scenario in which different external antigens incite multiple antigen-specific pathways, cytotoxic T cell responses, activation of classical complement cascade, and production of proinflammatory cytokines. […] No unequivocal evidence favoring or refuting these associations has been clearly proved, and today, the strict definition of JIA etiology remains unknown. […] The infection can represent a random event in a susceptible individual, or it can be a necessary factor in JIA development, always in combination with a peculiar genetic background.

• #3 Juvenile Idiopathic Arthritis (JIA) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/jra.html

  Juvenile idiopathic arthritis (JIA) is an autoimmune disease. This means that the bodys immune system, which normally attacks germs, mistakenly attacks the joints. This causes inflammation (swelling and irritation) in the joints and other problems. […] Doctors dont know exactly why kids and teens get JIA. Idiopathic means from an unknown cause. It can run in families but often does not. Its likely due to a combination of: genetic (inherited) causes, the way the immune system responds to infection and illness, a trigger such as an infection.

• #3 Juvenile Idiopathic Arthritis > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/juvenile-idiopathic-arthritis

  What causes juvenile idiopathic arthritis? […] The cause of JIA is unknown (idiopathic means relating to a disease for which there is no known cause), but research suggests genetics can be a factor. A small percentage of cases run in families, and you are 12 times more likely to develop JIA if your sibling has the disease.

• #3 Juvenile Idiopathic Arthritis (JIA) | Cause, Types & Treatment

  https://www.cincinnatichildrens.org/health/j/jia

  Children with juvenile idiopathic arthritis (JIA) have inflammation of the joints that is called arthritis. […] The exact cause is unknown. JIA is believed to be caused by a combination of genetic and environmental factors. Researchers think that something in the environment impacts or 'triggers’ the immune system, especially in people who have genetic factors that make them more likely to get arthritis. […] Although we still do not understand the exact cause of JIA, we have recently learned a great deal about what is responsible for chronic inflammation. We now know that three molecules called Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6) and Interleukin-1 (IL-1) are the major factors that keep inflammation in the joints active.

• #3 Juvenile idiopathic arthritis

  https://dermnetnz.org/topics/juvenile-idiopathic-arthritis

  JIA is recognised as having seven major subtypes, some of which exhibit the clinical and pathological features of other autoimmune disorders; these subtypes include: […] The exact cause of JIA is unclear, but a pronounced immune response in a perpetuating loop of both innate and adaptive immunity is believed to contribute to the pathogenesis of JIA. Aberrant activation of the innate immune system lead to the dysregulated production of proinflammatory cytokines. Tumour necrosis factor alpha (TNF-), interleukin (IL)-1, and IL-6 play a critical inciting role. […] Environmental factors may contribute to the development of JIA. Some studies have suggested associations with exposure to antibiotics, a bacterial infection in immunosuppressed individuals, and maternal smoking during pregnancy. […] Some studies have consistently supported associations between enthesitis-related JIA and human leukocyte antigen (HLA) polymorphisms; there appear to be increased associations, especially with early-onset disease. A monogenic form of systemic JIA with an underlying mutation in a regulatory protein involved in macrophage metabolism has been described.

• #3 Juvenile Idiopathic Arthritis (JIA) Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/10370-juvenile-idiopathic-arthritis

  Juvenile idiopathic arthritis (JIA) is an autoimmune disease in which your child’s immune system mistakenly targets the synovium (the tissue that lines the inside of the joint) and the synovial fluid in the joint. This causes the synovium to make extra fluid, which leads to swelling, pain and joint stiffness. […] Experts don’t yet know what causes JIA. In fact, the term idiopathic means unknown cause. Possible contributing factors may include: Environmental factors that influence your child’s immune system, Genetics, Infection.

• #3 Overview of Juvenile Idiopathic Arthritis

  https://openorthopaedicsjournal.com/VOLUME/14/PAGE/101/FULLTEXT/

  Juvenile Idiopathic Arthritis (JIA) is the most common cause of arthritis in childhood. […] The precise etiology of JIA is unknown, and is likely the result of a complex interaction between genetics and the environment. […] It is hypothesized that an environmental exposure in a genetically susceptible child leads to an altered immune response. […] The genetics of JIA have been extensively studied, and it is likely a polygenic disease. […] Furthermore, multiple studies have described an association between HLA alleles and both oligoarticular and polyarticular JIA. […] Genome-wide association studies have identified multiple single nucleotide polymorphisms that are associated with oligoarticular and RF negative polyarticular JIA, likely uniquely contributing to their pathogenesis. […] A possible theory for an environmental trigger is an infection as heat shock proteins are found to be elevated in JIA patients. […] However, no specific infection has yet been confirmed. Further studies are needed to describe the role of genetics and the environment in the pathogenesis of JIA.

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