Thymic function in juvenile idiopathic arthritis

Abstract

Objective:Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined.Methods:Thymic function was measured in 70 children and young adults with JIA (age range 2.1–30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4+ CD45RA+CD31+ T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the αTREC/ΣβTREC ratio. Lastly, regulatory T cells (TReg) of thymic origin (CD4+FOXP3+) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset.Results:Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)+ polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD.Conclusions:It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term “JIA” suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

Immune Aging and Autoimmune Diseases in Children

“…So far, two studies have aimed to analyze the naive T cells in children with JIA [17,78]. Both studies had a crosssectional study design and are only in part comparable because different classification systems were used and disease activity in the patient cohort was not identical.…”

“…To consider this definition of RTE, a study of 70 JIA patients (8 systemic onset, 10 polyarticular rheumatoid factor-positive, 12 polyarticular rheumatoid factor-negative, 27 persistent oligoarticular, 7 extended oligoarticular, 4 psoriatic and 2 enthesitis-associated JIA) analyzed TREC amounts in CD4+CD45RA+CD31+ T cells [18]. Following a mathematical model [80], the authors [78] calculated TRECs/ml blood as it directly reflects the reduction in thymic output and is not influenced by the dynamics of either TREC+ and TREC-cells. The proportion of these T cells with the CD31+ phenotype decreased with age in JIA and healthy controls, with the age-depend correlation of TRECs being less strong in JIA than in healthy controls [78].…”

“…Following a mathematical model [80], the authors [78] calculated TRECs/ml blood as it directly reflects the reduction in thymic output and is not influenced by the dynamics of either TREC+ and TREC-cells. The proportion of these T cells with the CD31+ phenotype decreased with age in JIA and healthy controls, with the age-depend correlation of TRECs being less strong in JIA than in healthy controls [78]. However, also CD4+CD45RA+CD31+ T cells can in part be maintained by peripheral T cell homeostasis [81] and, thus, may represent a less useful measure of thymic function in this setting [78].…”

Reply

“…It has been suggested that CD31 may be useful in defining recent thymic emigrants, since CD31ϩ T cells were shown to possess high numbers of TRECs (3). However, TRECs per milliliter of blood and percentages of CD4ϩCD45RAϩCD31ϩ T cells did not always correlate well, particularly in JIA patients (1). This supports the observation that several mechanisms, such as thymus dysfunction together with peripheral replication (4), cause quantitative changes to TREC numbers in patients with JIA.…”

T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders

“…In autoimmunity, T cells respond to antigenic challenge by clonal burst, therefore reducing the peripheral levels of TRECs [35]. For example, a decreased TREC level that was consistent with a low proportion of recent thymus emigrants was found in some polyarticular children with juvenile idiopathic arthritis [36].…”