Autoantibody response towards chromatin in patients with juvenile idiopathic arthritis

Objective Juvenile idiopathic arthritis (JIA) patients frequently exhibit antinuclear antibodies (ANAs), but the specific antigen target recognized by them and the presence of additional autoantibody specificities in JIA patients remains elusive. Methods Plasma samples from 110 untreated patients with active JIA, as well as from 14 children with unspecified arthritis and 151 age‐ and sex‐matched healthy children were analyzed with multiple modern clinical‐grade autoantibody assays, including automated indirect immunofluorescence to screen for ANAs with HEp‐2 cells, and specific immune assays to detect reactivity to individual autoantigens. In addition, a HuProt proteome microarray was used to screen for novel autoantibody targets in plasma samples from five ANA‐positive JIA patients and four ANA‐negative healthy controls. Results Homogeneous nuclear ANA staining, indicating reactivity towards chromatin, was detected in most (61.8%) JIA patients but rarely in healthy controls (2.7%; p<0.0001). No antibody reactivity to specific nuclear antigens or other autoantigens associated with connective tissue diseases was detected. However, 20% of JIA patients harbored antibodies against dsDNA‐nucleosome complexes (compared to 2.7% of controls, p<0.0001). Finally, the proteome microarray revealed core histone H2A variant H2AFY, part of the nucleosome, to be the most widely recognized human protein by autoantibodies of JIA patients. Conclusion Autoantibody reactivity in JIA primarily targets chromatin, but the epitopes targeted are likely either posttranslationally modified or multi‐molecule epitopes, such as dsDNA‐nucleosome complexes, rather than epitopes on individual native proteins or purified dsDNA.