title: Pemphigus vulgaris autoantibody response is linked to HLA-DQB1*0503 in Pakistani patients.
abstract: Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by an autoantibody response against an epidermal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hybridization. The results were compared with two separate ethnically matched control populations. WE found that PV patients from Pakistan had significantly increased frequencies of DRB1*1404 (p = 0.01), DQA1*0101 (p = 0.02), and DQB1*0503 (p = 0.01). Among the patients of non-Jewish European ancestry, DRB1*1401 (p < 10(-6)), DQA1*0101 (p < 10(-5)) and DQB1*0503 (p < 10(-6)), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV antibody was performed in 67 relatives of the 19 Pakistani patients. The results showed strong evidence for linkage of HLA-DRB1*1404, DQA1*0101, DQB1*0503, with the presence of PV antibody in relatives' families with a significant logarithm of the odds score of 6.06. Based on the three dimensional structure of class II molecules, we propose that HLA-DQA1*0101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with susceptibility to PV in non-Jewish populations.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Delgado
authors.forename: A
authors.initials: A
authors.lastname: Hameed
authors.forename: J J
authors.initials: JJ
authors.lastname: Yunis
authors.forename: K
authors.initials: K
authors.lastname: Bhol
authors.forename: A I
authors.initials: AI
authors.lastname: Rojas
authors.forename: S B
authors.initials: SB
authors.lastname: Rehman
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
authors.forename: C A
authors.initials: CA
authors.lastname: Alper
authors.forename: A R
authors.initials: AR
authors.lastname: Ahmed
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D002874:Chromosome Mapping; D004198:Disease Susceptibility / Q000276:immunology; D005060:Europe / Q000208:ethnology; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D015151:Immunoblotting; D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes / Q000235:genetics; D010154:Pakistan / Q000208:ethnology; D010375:Pedigree; D010392:Pemphigus / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015345:Oligonucleotide Probes