The Effect of PTPN22 Polymorphism on Juvenile Idiopathic Arthritis Subtypes and Disease Activity in a Finnish Study Population.

Abstract

Genetic factors that modulate immune regulation are increasingly recognised as contributors to the heterogeneity and clinical course of autoimmune diseases. Polymorphisms of protein tyrosine phosphatase non-receptor type 22 (PTPN22) are associated with several autoimmune diseases. We aimed to investigate the association of PTPN22 rs2476601 polymorphism (C1858T, R620W) with juvenile idiopathic arthritis (JIA) subtypes, disease activity and treatment response. A total of 105 patients with diagnosed JIA were recruited. Blood samples were collected, and PTPN22 polymorphism was analysed and compared to data from the 1000 Genomes. The PTPN22 rs2476601 A-allele was associated with increased JIA risk (OR: 1.71; 95% CI, 1.02-2.96; p = 0.043), while overall genotype frequency in patients did not significantly differ from controls (p = 0.086). Variant genotypes (AG/AA) were enriched in polyarticular JIA (p-JIA; OR: 2.27; 95% CI, 1.04-4.96; p = 0.037). All patients who developed uveitis had either ANA positivity or a PTPN22 variant genotype. None of ANA-negative patients with the PTPN22 wild-type genotype (GG) were diagnosed with uveitis (p = 0.044). Across three time points, disease activity improved significantly in both o-JIA and p-JIA. In o-JIA, ESR levels were persistently higher in the PTPN22 GG carriers. In contrast, in p-JIA, PTPN22 AG/AA genotype consistently showed higher active joint counts over time than those with GG genotype. Our present data deepen the understanding of the role of PTPN22 as a susceptibility factor in JIA, particularly in p-JIA. The observed associations suggest that PTPN22 polymorphism may contribute to disease heterogeneity and disease course in selected JIA subgroups.