# Autoantibodies Against Factor B and Factor H Without Pathogenic Effects in a Patient with Immune Complex-Mediated Membranoproliferative Glomerulonephritis

## TL;DR

A patient with immune complex-mediated glomerulonephritis has autoantibodies against complement factors B and H, but these antibodies do not cause harmful effects.

## Contribution

This study is the first to demonstrate that autoantibodies against complement factors B and H may not be pathogenic in immune complex-mediated MPGN.

## Key findings

- Autoantibodies against factor B and factor H were detected in the patient's serum.
- The autoantibodies did not influence complement activity or cause pathogenic effects in functional assays.
- The IgG fraction inhibited complement-mediated hemolysis, but free autoantibodies had minimal effects on complement function.

## Abstract

Background: Membranoproliferative glomerulonephritis (MPGN) is an umbrella term for chronic disorders affecting the glomeruli. MPGN is often accompanied by the presence of autoantibodies against complement components. However, the actual pathogenic effects of such autoantibodies, if any, are rarely studied. In this work, we investigated the role of anti-complement autoantibodies in an IC-MPGN patient. Methods: The presence of autoantibodies, their binding site, isotype, and titer were analyzed in ELISA. Antibody–antigen complexes were detected in the patient’s serum using Western blot. Autoantibodies were studied in functional assays to analyze their effects on C3 convertase, complement deposition, cofactor activity, C3b binding, and hemolysis. Results: We identified autoantibodies against factor B (FB) and factor H (FH) in the patient’s serum. Both FB-, and FH-autoantibodies were of IgG2, IgG3, IgG4, and IgGκ, IgGλ isotypes. FB-autoantibodies bound to the Ba and the enzymatically active Bb part of FB. FH-autoantibodies bound to the N- and C-termini of FH and cross-reacted with FHL-1 and FHR-1 proteins. In vivo formed complexes of the autoantibodies with both FB and FH were detected in the IgG fraction isolated from the serum. The autoantibodies did not influence solid-phase C3 convertase assembly and its FH-mediated decay. The free autoantibodies had no effect on complement deposition and on FH cofactor activity but slightly reduced C3b binding to FH. The IgG fraction of the patient dose-dependently inhibited complement-mediated rabbit red blood cell lysis, and the free autoantibodies decreased the solid phase C3 convertase activity. Conclusions: This case highlights that FB- and FH-autoantibodies are not necessarily pathogenic in IC-MPGN.