Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis.
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.
['Radanova|M|M|0000-0002-0941-6139', 'Mihaylova|G|G|', 'Ivanova|D|D|', 'Daugan|M|M|', 'Lazarov|V|V|', 'Roumenina|L|L|', 'Vasilev|V|V|']
D000328:Adult D000974:Antibodies, Antinuclear D000936:Antigen-Antibody Complex D001323:Autoantibodies D015331:Cohort Studies D003176:Complement C3 D003181:Complement C4 D018450:Disease Progression D006801:Humans D007074:Immunoglobulin G D007668:Kidney D008180:Lupus Erythematosus, Systemic D008181:Lupus Nephritis D011237:Predictive Value of Tests D011414:Properdin
lupus nephritis properdin complement