The complement system and human autoimmune diseases

Genetic deficiencies of early components of the classical complement activation pathway (especially C1q, r, s, and C4) are the strongest monogenic causal factors for the prototypic autoimmune disease systemic lupus erythematosus (SLE), but their prevalence is extremely rare. In contrast, isotype genetic deficiency of C4A and acquired deficiency of C1q by autoantibodies are frequent among patients with SLE. Here we review the genetic basis of complement deficiencies in autoimmune disease, discuss the complex genetic diversity seen in complement C4 and its association with autoimmune disease, provide guidance as to when clinicians should suspect and test for complement deficiencies, and outline the current understanding of the mechanisms relating complement deficiencies to autoimmunity. We focus primarily on SLE, as the role of complement in SLE is wellestablished, but will also discuss other informative diseases such as inflammatory arthritis and myositis.

Automated summary

Genetic deficiencies of early components of the classical complement activation pathway, such as C1q, r, s, and C4, play a significant role in the development of systemic lupus erythematosus (SLE). However, their prevalence is rare, while isotype genetic deficiencies of C4A and acquired deficiency of C1q by autoantibodies are more common in SLE patients. This review discusses the genetic basis of complement deficiencies in autoimmune disease, focusing on SLE and its established relationship with complement, but also touching upon other informative diseases like inflammatory arthritis and myositis.