The unprecedented variations of GCNs with high frequencies of homozygous or heterozygous deficiency of C4A or C4B, and continuous variations in copy-numbers from one to four copies of C4 genes on each copy of chromosome 6 (or haplotype) among healthy subjects and SLE patients inevitably pose great challenges both technically and conceptually: the former for accurate data acquisition and the latter for accurate data interpretation. This evidence concerns the gene C4B and systemic lupus erythematosus.