Anti-CENP-A/B reactivity in samples exhibiting the centromere HEp-2 pattern is associated with a lower frequency of interstitial lung disease in limited cutaneous systemic sclerosis patients

Abstract

Introduction: Anti-centromere antibodies are associated with limited cutaneous systemic sclerosis (lcSSc) and a more favorable prognosis. The centromere HEp-2 pattern (AC-3) suggests the presence of antibodies against CENP antigens, mainly CENP-B/A. This study analyzed clinical and demographic associations of anti-centromere antibodies in a cohort of patients exclusively with the lcSSc form of SSc. The frequency of CENP-B and CENP-A reactivity in samples with the AC-3 pattern was also evaluated. Method: Samples from 38 lcSSc patients with AC-3 were evaluated for reactivity to CENP-B/A using line-blot and ELISA. Clinical data from 68 lcSSc patients (20 AC-3 and 48 Non-AC-3) were analyzed. Results: Of the AC-3 samples, 84% and 82% were reactive against CENP-B and CENP-A, respectively, by line-blot, and 92% were positive for CENP-B by ELISA. Concordance for CENP-B reactivity between ELISA and line-blot was 79%. Reactivity to both CENP-B and CENP-A was found in 68% of AC-3 samples, while one sample was positive only for CENP-A. Overall, 97% of AC-3 samples were reactive to CENP-B, and all were reactive to either CENP-B or CENP-A. Clinically, interstitial lung disease (ILD) was less frequent in AC-3 patients compared to Non-AC-3 (10.5% vs. 54.2%; p = 0.001). Other organ involvement frequencies were similar. Conclusion: ILD was less frequent in lcSSc patients with a positive AC-3 pattern as compared to those with a non-AC-3 pattern, which could suggest a less severe prognosis. In addition, anti-CENP-B was the predominant autoantibody in samples yielding the AC-3 pattern, but anti-CENP-A reactivity was also prevalent, and exclusive anti-CENP-A reactivity was also observed.