C1R and rheumatoid arthritis: Although it is a multifactorial disease, there is an overwhelming clinical evidence showing that homozygous deficiency in any of the classical pathway proteins – C1q, C1r, C1s, C4, and C2 – predisposes an individual to develop SLE and other autoimmune diseases such as rheumatoid arthritis (RA) (31, 33, 37).