Anti-CENP-B polarity divides SLE: divergent clinical-immune phenotypes and distinct treatment responses

TL;DR

Anti-CENP-B antibodies in SLE patients define a distinct subset with unique clinical features and treatment responses.

Contribution

Identifies anti-CENP-B-positive SLE as a distinct subset with divergent clinical-immune profiles and treatment responses.

Findings

Anti-CENP-B-positive SLE patients show older age at onset, less lupus nephritis, and more Raynaud’s phenomenon.

These patients have distinct immunological features including lower anti-dsDNA and higher IgG and B-cell counts.

Treatment responses differ significantly between anti-CENP-B-positive and -negative SLE patients.

Abstract

Anti-CENP-B antibodies (anti-CENP-B), directed against centromere protein B, are a serological hallmark of limited cutaneous systemic sclerosis (lcSSc) but are only occasionally encountered in systemic lupus erythematosus (SLE). When detected in SLE they may create diagnostic ambiguity. Since autoantibody-defined SLE subsets exhibit distinct phenotypes, delineating the clinical and immunological features of anti-CENP-B-positive disease is essential for precise management.

We retrospectively collected demographic, clinical, laboratory and therapeutic data from 310 SLE patients including 73 anti-CENP-B-positive patients and 237 anti-CENP-B-negative patients. Inter-group differences, correlations, and multivariable logistic regression were performed.

Compared with the anti-CENP-B-negative patients, the anti-CENP-B-positive patients were older, less frequently had lupus nephritis (LN), but more often exhibited Raynaud’s phenomenon, cardiac, or pleuropulmonary involvement. Serologically, they displayed lower anti-dsDNA, anti-nucleosome and anti-histone antibody levels, reduced C4, yet higher IgA, IgM, and IgG concentrations and expanded CD19+ B-cell numbers; accordingly, SLEDAI-2K scores and 24-h urinary protein (24h-UTP) were lower. C4 inversely correlated with disease activity indices and IgG in the positive group, whereas in the negative group it also correlated with B-cell counts and IgM levels. Multivariate logistic regression identified age, Raynaud’s phenomenon, CD19+ B-cell count, and IgG level as factors independently associated with anti-CENP-B positivity. Compared with their anti-CENP-B–negative patients, anti-CENP-B–positive SLE patients displayed a markedly divergent therapeutic response.

Anti-CENP-B positivity defines a distinct SLE subset characterized by older age at onset, milder renal involvement, Raynaud’s phenomenon, and specific humoral alterations; importantly, these patients also show a treatment response that differs significantly from that of the anti-CENP-B-negative group, underscoring the imperative for personalized, precision therapy.

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