Detection of IgE-autoantibodies to nuclear antigens in patients with systemic sclerosis and analysis of their clinical relevance

Abstract

ObjectivesAntinuclear antibodies (ANA) of the IgE-type have been described in several connective tissue disorders (CTD) but not yet in systemic sclerosis (SSc). Aim of the study was, therefore, to establish an ELISA for the demonstration of IgE-autoantibodies to topoisomerase-I (topo-I) and the centromeric proteins A and B (CENP-A/B), to assess their prevalence and reactivity in SSc and to analyse their clinical relevance. Methods One hundred fifty-one patients with SSc and 88 with CREST-syndrome, 291 patients with other CTD, and 23 patients withfibromyalgia syndrome (FM) as a control collective were included into the study. Patients' sera were analysed by an in-house-ELISA for IgE autoantibodies against topo-I and CENP-A/B using recombinant antigens. Patients were assessed for median Rodnan skin score(mRSS), different organ and cutaneous manifestations. Results Of the patients with CREST syndrome, 67% had IgE-anti-CENP-A-and 77% IgE-anti-CENP-B-antibodies. IgE-anti-topo-Iantibodies were found in 56% of patients with SSc. Prevalence and reactivity were significantly higher in CREST and SSc, respectively, than in other CTD or FM. IgE-reactivity strongly correlated with IgG-antibody reactivity. In CRESTsyndrome, IgE-anti-CENP-A (but not CENP-B)-antibodies were significantly higher and more prevalent in patients with skin ulcers, high mRSS, and more than four organ manifestations. They did not correlate with blood eosinophil counts.In contrast, for IgE-anti-topo-I antibodies no correlation with clinical manifestations was observed. Conclusion IgE-autoantibodies against CENP-A/B and topo-I occur in SSc underlining the concept that SSc may be a T helper cell type2 mediated disease. IgE-anti-CENP-A-antibodies correlated with disease activity, but this has to be confirmed in larger studies.