Oligoarticular and polyarticular JIA: Epidemiology and pathogenesis

Department of Pediatrics, Stanford University, Stanford, CA 94305-5164, USA.
Nature Reviews Rheumatology (Impact Factor: 9.85). 10/2009; 5(11):616-26. DOI: 10.1038/nrrheum.2009.209
Source: PubMed


Juvenile idiopathic arthritis (JIA) refers to a group of chronic childhood arthropathies of unknown etiology, currently classified into subtypes primarily on the basis of clinical features. Research has focused on the hypothesis that these subtypes arise through distinct etiologic pathways. In this Review, we discuss four subtypes of JIA: persistent oligoarticular, extended oligoarticular, rheumatoid-factor-positive polyarticular and rheumatoid-factor-negative polyarticular. These subtypes differ in prevalence between ethnic groups and are associated with different HLA alleles. Non-HLA genetic risk factors have also been identified, some of which reveal further molecular differences between these subtypes, while others suggest mechanistic overlap. Investigations of immunophenotypes also provide insights into subtype differences: adaptive immunity seems to have a prominent role in both polyarticular and oligoarticular JIA, and the more-limited arthritis observed in persistent oligoarticular JIA as compared with extended oligoarticular JIA may reflect more-potent immunoregulatory T-cell activity in the former. Tumor necrosis factor seems to be a key mediator of both polyarticular and oligoarticular JIA, especially in the extended oligoarticular subtype, although elevated levels of other cytokines are also observed. Limited data on monocytes, dendritic cells, B cells, natural killer T cells and neutrophils suggest that the contributions of these cells differ across subtypes of JIA. Within each subtype, however, common pathways seem to drive joint damage.

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    • "Clearly, HLA and non- HLA susceptibility genes may enhance disease acquisition, severity, and response to treatment. Single gene microsatellites and nucleotide polymorphisms, such as variations in PTPN22, STAT4, and TRAF1-C5, may be independent risk factors [6] [10] [11]. Environmental factors that contribute to adult rheumatoid arthritis (RA) include cigarette smoking and certain infectious agents. "
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    ABSTRACT: We describe the development of rheumatoid factor-positive migratory polyarthritis in a 5-year-old male who had been administered bidaily oral mineral oil as a laxative since birth. Minor respiratory symptoms, radiographic and bronchoscopic findings were consistent with chronic lipoid pneumonia. We speculate that immune sensitization to mineral oil promoted the clinical syndrome of juvenile idiopathic arthritis.
    07/2015; 2015:1-3. DOI:10.1155/2015/403109
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    • "This pathogenetic process results in chronic inflammation of the joint [21]. Consequently high levels of pro-inflammatory cytokines in serum and inflamed joint were found in patients with oligoarticular JIA [3]. Therapeutic strategies block T cell dependent immune responses and consequently repress the process of autoimmunity. "

    World Journal of Vaccines 01/2014; 04(03):133-146. DOI:10.4236/wjv.2014.43016
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    • "Our findings are consistent with the hypothesis that dysregulation of the innate immune system makes a more prominent contribution to SJIA immunopathology than alterations of the adaptive immune system [17,63], whereas adaptive responses are thought to drive oligoarticular and polyarticular JIA [64,65]. However, our results implicate deficiencies in genes associated with T cell-related responses in SJIA pathology, similar to observations in other studies [29]. "
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    ABSTRACT: Background Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA) compared to polyarticular juvenile idiopathic arthritis (POLY). We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR) and number of affected joints (joint count, JC). Methods PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t-test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC) in SJIA or POLY samples. These transcripts were used to find related biological pathways. Results Combining Pearson and t-test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF) of SJIA compared to samples from the later arthritis-predominant phase (AF). Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF) subgroup. Conclusions The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with differences in clinically appreciated target organs. The limited number of ESR-related SJIA genes that also are associated with elevations of ESR in POLY implies that the SJIA associations are specific for SJIA, at least to some degree. The distinct pathways associated with arthritis in early and late SJIA raise the possibility that different immunobiology underlies arthritis over the course of SJIA.
    BMC Medicine 10/2012; 10(1):125. DOI:10.1186/1741-7015-10-125 · 7.25 Impact Factor
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