Central MHC genes, IgA deficiency and autoimmune disease

IgA deficiency is a common immunological disorder that is sometimes associated with an immunodeficiency syndrome, allergic disease, autoimmune disease and gluten enteropathy. Many subjects with this deficiency, however, are healthy, at least for many decades. Analysis of the immunological and genetic abnormalities found in IgA deficiency and in some of the associated disorders has led to the postulate that a genetically determined defect of immunoregulation underlies all of these diseases. Here, Martyn French and Roger Dawkins propose that the products of genes located within the central region of the major histocompatibility complex (MHC) regulate B cells and/or antibody production. Particular MHC ancestral haplotypes contain specific alleles and arrangements of these genes, thereby explaining associations with either increased or decreased production of immunoglobulin isotypes by B cells.