Autoantibodies to complement components in C3 glomerulopathy and atypical hemolytic uremic syndrome

• Autoantibodies to complement proteins are relevant to kidney diseases and treatment.
• Pathogenic factor H autoantibodies are common in aHUS, rare in C3 glomerulopathy.
• C3 nephritic factor is common in C3 glomerulopathy, but detection is challenging.
• Autoantibodies to factor B, factor I and C3b are rare, with unknown significance.

The alternative pathway of complement is implicated in the pathogenesis of several renal diseases, such as atypical hemolytic uremic syndrome, dense deposit disease and other forms of C3 glomerulopathy. The underlying complement defects include genetic and/or acquired factors, the latter in the form of autoantibodies. Because the autoimmune forms require a specific treatment, in part different from that of the genetic forms, it is important to detect the autoantibodies as soon as possible and understand their characteristics. In this overview, we summarize the types of anti-complement autoantibodies detected in such diseases, i.e. autoantibodies to factor H, factor I, C3b, factor B and those against the C3 convertases (C3 nephritic factor and C4 nephritic factor). We draw attention to newly described autoantibodies and their characteristics, and highlight similarities and differences in the autoimmune forms of these diseases.