Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis

Author:

Radanova M1ORCID,Mihaylova G1,Ivanova D1,Daugan M2,Lazarov V3,Roumenina L2,Vasilev V3

Affiliation:

1. Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, Varna, Bulgaria

2. INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université de Paris, Paris, France

3. Clinic of Nephrology, University Hospital “Tzaritza Yoanna, ISUL”, Medical University of Sofia, Sofia, Bulgaria

Abstract

Summary Properdin is the only positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE) suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22·5% of the LN patients (16 of 71) by enzyme-linked immunosorbent assay (ELISA). The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and anti-nuclear antibodies and low concentrations of C3 and C4 in patients, and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are negative for both anti-properdin and anti-dsDNA will not have severe nephritis. Immunoglobulin G from anti-properdin-positive patients’ plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti-properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.

Funder

Bulgarian National Science Fund

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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