The first example of anti-Chido was studied both in Minneapolis and London in 1962. Six other examples were identified in 1964 and 1965. The antibody was officially reported in 1967 and named after one of the early patients. Nine years later a similar and related antibody was described, ie. anti-Rodgers. Initially it was believed that these might be white cell or HLA antibodies. When the first several antibody producers were HLA typed, it was found that they all had the HLA-A1,B8 phenotype. In addition, human plasma was able to inhibit both of these antibodies. Finally, in 1978 the association became clear when it was shown that both Chido (Ch) and Rodgers (Rg) were epitopes carried on the fourth component of complement (C4). The genes for C4 are closely linked to the HLA genes.

The C4 protein can exist in two forms known as C4A and C4B which have some functional differences related to amino acid changes. The amino acid changes which code for the 6 known Ch antigens, the two Rg antigens and a third antigen known as WH were identified at the molecular level by Yung Yu and Carolyn Giles. Today approximately 30 different forms of C4A and C4B have been identified and studied worldwide. Approximately 2% of the population will completely lack either C4A (Rg negative) or C4B (Ch negative) and appear to be healthy. However, an increased frequency of null alleles (lacking the protein) for C4A or C4B have been associated with some autoimmune disease such as systemic lupus erythematosus (SLE). The rare C4-deficient phenotype in this system is both Ch and Rg negative and lacks both C4A and C4B in the plasma. Only about 20 such individuals have been reported in the literature and many of them have had SLE.