Multiple therapeutic agents that target the complement system are currently investigated in various autoimmune and inflammatory disorders: (i) Regarding autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, vasculitides, Sjögren’s syndrome, and systemic sclerosis evidence revealed that dysregulated complement activation is involved in the pathogenesis, particularly C3, C5aR, CR2, and MAC. This evidence concerns the gene CR2 and autoimmune disease.