Evidence for a genetic influence was noted very early in the study of CVI, when family studies disclosed that a significant number of patients had first-degree relatives with other immunologic diseases such as isolated IgA deficiency and various autoimmune diseases. Recent studies have found an association of CVI and IgA deficiency with certain major histocompatibility complex (MHC) haplotypes. These results suggest that CVI and IgA deficiency are related disorders, susceptibility to which is determined by a gene or genes in or near the MHC region.

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