BASIC AND TRANSLATIONAL RESEARCH

Thymic function in juvenile idiopathic arthritis

A R Lorenzi, T A Morgan, A Anderson, J Catterall, A M Patterson, H E Foster, J D Isaacs

Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK

Professor J D Isaacs, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK; j.d.isaacs{at}ncl.ac.uk

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 TREC/βTREC ratio. Lastly, regulatory T cells (T_Reg) 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.

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