C4 CN studies in autoimmunity have been mainly focused on SLE providing no definitive results14,22,25 in part due to the complexity of the genetic variation of C4A and C4B and the high linkage disequilibrium (LD) of the MHC locus, which contains the HLA genes, the strongest genetic associations with most autoimmune diseases including SLE, RA, and SSc6,26,27. This evidence concerns the gene C4A and autoimmune disease.