Major Histocompatibility Complex Haplotype Studies in Ashkenazi Jewish Patients with Pemphigus Vulgaris

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-10, Vol.87 (19), p.7658-7662
• Main Authors: Ahmed, A. Razzaque, Yunis, Edmond J., Khatri, Khalil, Wagner, Rene, Notani, Gur, Awdeh, Zuheir, Alper, Chester A.
• Format: Article
• Language: English
• Subjects: Alleles; Antibodies; Autoimmune diseases; Biological and medical sciences; Disease susceptibility; DNA Probes; Ethnic Groups; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Frequency; Genetic inheritance; Haplotypes; Heterozygotes; HLA Antigens - genetics; HLA B antigens; Homozygote; Homozygotes; Humans; Jews; Major Histocompatibility Complex; Pemphigus; Pemphigus - genetics; Pemphigus - immunology; Reference Values; Restriction Mapping
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.19.7658

Of 26 Ashkenazi Jewish patients with pemphigus vulgaris, 24 (92.3%) carried the major histocompatibility complex (MHC) class II alleles HLA-DR4, DQw3, of which all were of the subtype DR4, DQw8. From Studies of the patients and their families, haplotypes were defined. It was found that, of the patients who carried HLA-DR4, DQw8, 75% carried one or the other (and in one case, both) of two haplotypes [HLA-B38, SC21, DR4] or HLA-B35, SC31, DR4. The former is a known extended haplotype among normal Jews, with a frequency of 0.102, and the latter may also be an extended haplotype in this ethnic group, with a frequency of 0.017 among normal haplotypes from Jews. Of the remaining DR4-positive patients, all but one had a presumed D-region segment (defined a sSC21, DR4, DQw8 or SC31, DR4, DQw8 with variable HLA-B) of these haplotypes. Only one patient had DR4, DQw8 without any other markers of the extended haplotypes. The number of homozygotes and heterozygotes for DR4, DQw8 was consistent with dominant but not recessive (P < 0.01) inheritance of a class II-linked susceptibility gene for the disease. Since the disease is entirely attributable to the presence of an antibody to an intraepidermal intercellular cement substance, it is likely that the case II susceptibility gene (on [HLA-B38, SC21, DR4, DQw8], HLA-B35, SC31, DR4, DQw8, or their segments, in Jewish patients) controls the production of the antibody as a dominantly expressed immune response gene.