Clinical and functional consequences of anti-properdin autoantibodies in
patients with lupus nephritis
Properdin is the only one 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 (16/71) by 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 ANA and to 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 both negative for anti-properdin and anti-dsDNA will not have severe
nephritis. IgG 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.