Presence and reactivities of antibodies directed to citrullinated peptides in a Swedish JIA cohort

Juvenile idiopathic arthritis is a heterogeneous group of chronic inflammatory joint diseases in children. The presence and role of antibodies targeting citrullinated proteins remains unclear in this patient group. This study aimed to assess antibodies against citrullinated peptides in a Swedish cohort of patients with juvenile idiopathic arthritis and to explore their associations with clinical features and genetic markers. Plasma samples from 334 patients with juvenile idiopathic arthritis were analyzed for antibodies against cyclic citrullinated peptides using enzyme-linked immunosorbent assay. A subset of 100 patients underwent detailed profiling of antibody reactivity to 15 citrullinated peptides and their non-citrullinated counterparts using a multiplex microarray. Rheumatoid factor, antinuclear antibodies, and HLA-DRB1 genotypes were also assessed. Antibodies against cyclic citrullinated peptides were detected in 6.2% of patients, with the highest prevalence in the rheumatoid factor–positive polyarthritis subtype. These patients were older at disease onset and more frequently carried HLA-DRB1 shared epitope alleles. Among the 100 profiled patients, 85% of those positive for cyclic citrullinated peptide antibodies showed reactivity to at least one citrullinated peptide, compared to 19% of antibody-negative patients. The most frequent reactivities were directed against peptides derived from filaggrin, fibrinogen, vimentin, and enolase. Reactivity to non-citrullinated peptides was minimal. A significant association was found between reactivity to citrullinated vimentin and the presence of HLA-DRB1 shared epitope alleles. This study reveals a distinct pattern of antibody reactivity to citrullinated peptides in a subset of patients with juvenile idiopathic arthritis, suggesting a biologically distinct subgroup with similarities to adult rheumatoid arthritis. These findings identify ACPA-positive JIA as a unique subgroup of young patients and underscore an opportunity to investigate early molecular events driving the immune response to citrullinated proteins and the pathogenesis of arthritis.