Oligoarticular and polyarticular JIA: epidemiology and pathogenesis

Abstract

Summary Juvenile idiopathic arthritis (JIA) refers to a group of chronic childhood arthropathies, 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 appears 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 also are 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 appear to drive joint damage.

Distinct Cytokine Profiles in Patients with Oligoarticular Juvenile Idiopathic Arthritis after <i>in</i> <i>Vitro</i> Blockade of T Cells by Cyclosporine and Abatacept

“…After PHA-stimulation we found an increase of IL-17 in the oJIA-group, while in healthy control subjects no relevant concentration of this cytokine was observed. This supports the hypothesis of association between IL-17/CD4 + Th17 cells and autoimmune mechanisms in the pathogenesis of oJIA postulated by many studies [3] [8]. After blocking T cell function via cyclosporine IL-17 concentration is undetectable low.…”

“…Present data suggest an autoimmune pathogenesis involving both adaptive and innate immune responses. The association between susceptibility to oligoarticular JIA and HLA class II alleles implicates CD4 + T cells in the pathogenesis of chronic arthritis [3]. This is supported by the fact that activated CD4 + T cells clustered around dendritic cells are found in the synovia of the inflamed joint in oligoarticular JIA patients [4].…”

“…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].…”

Nerve Growth Factor Downregulates Inflammatory Response in Human Monocytes through TrkA

“…JIA is a term that collectively refers to a group of chronic childhood arthropathies that represent the most common rheumatic condition in children (26). Twenty-five children with JIA were included in the study.…”

Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis

“…Several immunologic abnormalities have been characterized both in patients with rheumatoid arthritis (RA) (16) and in children with JIA (17,18). Many of these abnormalities are common to both diseases, whereas others are related to a specific disease subtype.…”