Mapping of B-cell epitopes recognized by antibodies to histones in subsets of juvenile chronic arthritis

The sera of 138 patients with juvenile chronic arthritis (JCA) were tested in ELISA with the five individual histones, 34 histone peptides covering the full length of the four core histones, and two peptides corresponding to the N- and C-terminal domains of H1. The occurrence of IgG antibodies was examined regarding the different subsets of JCA (pauciarticular, polyarticular, and systemic onset) and regarding clinical features (chronic anterior uveitis, CAU) and other serological features (antinuclear antibodies, ANA). Seventy-two percent of the 138 sera reacted with at least 1 histone peptide. The peptides 204-218 of H1, 1-25 of H2B, and 111-130 of H3 were recognized by 22-28% of JCA sera, and 42% of JCA sera reacted with one or both peptides 1-25 of H2B and 111-130 of H3. The frequency of occurrence of anti-histone antibodies (AHA) regarding the type of histone fraction (H1, H2A, H2B, H3 and H4) or the regions of histones was not significantly different in the three subsets of JCA. No obvious association was found between IgG antibodies to histone peptides and uveitis. In the subset of pauciarticular JCA, 13/31 patients (41.9%) with CAU against 14/41 patients (34.1%) without CAU possessed IgG antibodies reacting with peptides of the C-terminal domain 83-135 of H3. This difference is not statistically significant. Finally, the presence of antibodies to histones and histone peptides cannot completely explain ANA reactivity found in patients' sera. Although antibodies to histone peptides occur frequently in the serum of children with JCA, the antibody profiles seem to be highly individual and do not correlate with disease subtype or activity. Identification of AHA present not only in the circulation but also in tissue deposits may provide better insight into the identification of pathogenic antibodies.