Oligoarticular and polyarticular JIA: epidemiology and pathogenesis.

Department of Pediatrics, Stanford University, Stanford, CA 94305-5164, USA.
Nature Reviews Rheumatology (Impact Factor: 10.25). 10/2009; 5(11):616-26. DOI: 10.1038/nrrheum.2009.209
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B-cell targeted therapy in JIA.
    12/2010; 2010:759868. DOI:10.1155/2010/759868
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: CD8T cells lacking CD28 were originally reported by Wedderburn and colleagues as a characteristic feature of JIA, but the relevance of these unusual cells to JIA remains to be elucidated. Because of recent evidence that CD28 loss is typical of terminally differentiated lymphocytes, we examined for functional subsets of CD8T cells in JIA. Methods: Following informed consent/assent, blood and/or waste synovial fluid were collected from children with definite diagnosis of JIA (n = 98). De-identified blood (n = 33) and cord blood (n = 13) samples from healthy donors were also collected. CD8T and CD4T cells were screened for novel receptors, and where indicated, bioassays were performed to determine functional relevance of the identified receptor. Results: Patients had a naïve T cell compartment with shortened telomeres, and their entire T cell pool had reduced proliferative capacity. They had an over abundance of CD31(+) CD28(null) CD8T cells, which was a significant feature of oligoarticular JIA (n = 62) compared to polyarticular JIA (n = 36). CD31(+) CD28(null) CD8T cells had limited mitotic capacity, and expressed high levels of the senescence antigens γH2Ax and/or p16. Ligation of CD31, independent of the TCR, sufficiently induced tyrosine phosphorylation, vesicle exocytosis, and production of IFN-γ and IL-10. Conclusion: These data provide the first evidence for cell senescence, represented by CD31(+) CD28(null) CD8T cells, in the pathophysiology of JIA. Activation of these unusual cells in a TCR-independent manner suggests they are maladaptive, and could be potential targets for immunotherapy. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 08/2013; 65(8). DOI:10.1002/art.38015 · 7.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The incidence and prevalence of juvenile idiopathic arthritis (JIA) vary widely across the world but data in East Asia is lacking. Uveitis is a serious cause of morbidity in JIA. This study aimed to analyze the incidence and prevalence of JIA, and the characteristics of JIA-associated uveitis in Taiwan. A population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. Each patient was individually tracked from 1999 to 2009 to identify the diagnosis of JIA and uveitis using the International Classification of Diseases diagnostic codes. Multivariate logistic regression was used to determine the risk factors and complications of uveitis in patients with JIA. The study cohort had 2636 cases of JIA and included juvenile rheumatoid arthritis (57.7%), enthesitis-related arthritis (ERA) (39.2%), and psoriatic arthritis (3.1%). The average annual incidence of JIA and JIA-associated uveitis were 4.93 (range, 3.93-6.23) and 0.25 (range, 0.12-0.37) cases per 100,000 population, respectively. The average period prevalence of JIA was 33.8 cases per 100,000 population. Uveitis occurred in 4.7% of patients with JIA, while JIA-associated uveitis was complicated by cataract (11.2%) and glaucoma (24.8%). Enthesitis-related arthritis was significantly associated with uveitis (OR: 3.47; 95% CI: 2.24-5.37) (p<0.0001). Uveitis diagnosed before JIA was the most significant risk factor for complications of glaucoma or cataract (OR: 3.54; 95% CI: 1.44-8.72) (p = 0.006). The incidence of JIA is low but that of JIA-associated uveitis is increasing. Higher percentage of males in patients with ERA and the strong association between ERA and uveitis are unique for children with JIA in Taiwan. Uveitis diagnosed before arthritis is an important risk factor for complications. Continuous ophthalmologic follow-up is needed for children with JIA or uveitis of unknown etiology.
    PLoS ONE 08/2013; 8(8):e70625. DOI:10.1371/journal.pone.0070625 · 3.53 Impact Factor