Functional and prognostic relevance of the −173 polymorphism of the macrophage migration inhibitory factor gene in systemic‐onset juvenile idiopathic arthritis

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Abstract
Objective: To address the functional and prognostic relevance of the −173 single‐nucleotide G‐to‐C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic‐onset juvenile idiopathic arthritis (systemic‐onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease.Methods: A total of 136 patients with systemic‐onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF‐173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme‐linked immunosorbent assay. The evaluation of the association of the MIF‐173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C‐HAQ); and 3) data concerning the treatment regimens during the disease course.Results: Systemic‐onset JIA patients carrying a MIF‐173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF‐173*C allele than in MIF‐173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF‐173*C allele. At the last visit, the numbers of joints with active arthritis, the C‐HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF‐173*C allele.Conclusion: Our study shows the functional relevance of the MIF‐173 polymorphism and suggests that the MIF‐173*C allele is a predictor of poor outcome in systemic‐onset JIA.