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  • Review Article
  • Published:

Oligoarticular and polyarticular JIA: epidemiology and pathogenesis

Nature Reviews Rheumatology volume 5, pages 616–626 (2009)Cite this article

Abstract

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.

Key Points

  • Epidemiologic, genetic and immunophenotypic evidence suggests that oligoarticular (persistent and extended) and polyarticular (rheumatoid factor positive and negative) subtypes of juvenile idiopathic arthritis (JIA) are distinct etiopathological conditions

  • Reported incidence and prevalence of JIA vary widely, due partly to a lack of specific diagnostic tests and to the rarity of community-based studies

  • Inherited susceptibility factors (both HLA and non-HLA) generally differ among JIA subtypes, although the presence of some overlap in the latter suggests shared immunological pathways

  • Evidence supports a key role for T-cell-driven inflammation in oligoarticular and polyarticular JIA and suggests a contribution of regulatory T cells to limiting disease in persistent oligoarticular JIA

  • Dysregulation of cytokines, especially tumor necrosis factor, contribute to oligoarticular and polyarticular JIA pathogenesis, and persistent cytokine abnormalities suggest that clinical remission is a state of compensated inflammation

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Acknowledgements

We apologize to colleagues whose work could not be cited due to space constraints. We thank Dr Daniel Lovell (Cincinnati Children's Hospital Medical Center, Division of Rheumatology) for helpful comments and Ariana Peck for assistance with bibliographical research. This work was supported by funding from the NIH, the Dana Foundation and the Wasie Foundation. D. Milojevic was supported by the American College of Rheumatology Research and Education Foundation Academic Re-entry Award. J. L. Park is supported by the American College of Rheumatology Research and Education Foundation Physician Scientist Development Award; she was also supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The content of this Review is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the NIH.

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  1. Department of Pediatrics, Stanford University, Stanford, CA, USA

    Claudia Macaubas, Khoa Nguyen, Jane L. Park & Elizabeth D. Mellins

  2. Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA

    Diana Milojevic

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Macaubas, C., Nguyen, K., Milojevic, D. et al. Oligoarticular and polyarticular JIA: epidemiology and pathogenesis. Nat Rev Rheumatol 5, 616–626 (2009). https://doi.org/10.1038/nrrheum.2009.209

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