Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients.

Highlights

  • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a prevalence of 4/ 10,000 among Northern Europeans and a predisposition of women of childbearing age [1]

  • The median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4. 88 patients were classified in the “low disease activity” group and 77 in the “high disease activity” group, as previously defined

  • Our study is to our knowledge the first one assessing the presence of antibodies targeting ficolin-3 and measuring their titers using an ELISA method in SLE patients

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Summary

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a prevalence of 4/ 10,000 among Northern Europeans and a predisposition of women of childbearing age [1]. Molecules of importance in the uptake of dying cells could have a role in host protection against autoimmune diseases, including SLE [5] [6] [7] [8]. Apart from its well characterized anti-microbial role, the complement system has a pivotal role in maintaining host integrity by eliminating apoptotic and damaged cells as well as by clearing circulating immune complexes [9]. Mice deficient for C1q, the recognition protein of the classical complement pathway, are predisposed to SLE-like diseases [10] and human studies report that hereditary homozygous deficiencies of C1q are strongly associated with susceptibility to SLE, with a defect in apoptotic cells uptake by macrophages in SLE patients [11]. MBL-null mice exhibit defective clearance of apoptotic cells, they fail to develop symptoms of autoimmune diseases, suggesting the ability of other molecules to compensate for MBL deficiency [14]

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