Reduced IgM natural autoantibody levels against heat shock proteins are associated with disease severity in juvenile idiopathic arthritis.

Introduction: Natural autoantibodies (nAAbs) contribute to immune homeostasis and may be altered in patients with autoimmune diseases. While anti-heat shock protein (Hsp) antibodies have been previously described in juvenile idiopathic arthritis (JIA), their relationship with disease severity and treatment effects during remission remains unclear. This study aimed to measure the serum levels of IgM and IgG nAbs against heat shock protein (Hsp) 60 and Hsp70 in children with JIA in remission (mean age: 7.41 years, range:1.27-14.54 years) and to explore their associations with disease subtype, severity, and treatment. Methods: Serum samples from 47 children with JIA in remission and 22 apparently healthy controls (HC) were analyzed. Patient groups were stratified according to the treatment regimen (methotrexate monotherapy versus methotrexate plus adalimumab) and disease subtype and severity. Anti-Hsp60 and anti-Hsp70 IgM and IgG antibodies were measured u Results: No significant differences in anti-Hsp60 or anti-Hsp70 nAAb levels were observed between patients with JIA and apparently healthy controls or between treatment groups. However, severity-based analyses revealed significantly lower anti-Hsp60 and anti-Hsp70 IgM levels in patients with polyarticular JIA than in those with milder oligoarticular forms and in apparently healthy controls. No significant differences were observed in the anti-Hsp60 or anti-Hsp70 IgG levels. Conclusion: Reduced levels of natural IgM autoantibodies against Hsp60 and Hsp70 are associated with more severe JIA phenotypes during remission, supporting the potential immunoregulatory and protective roles of natural IgM autoantibodies in JIA.