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  • Title: Role of MHC Class II genes in the pathogenesis of pemphigoid.
    Author: Zakka LR, Reche P, Ahmed AR.
    Journal: Autoimmun Rev; 2011 Nov; 11(1):40-7. PubMed ID: 21782980.
    Abstract:
    Pemphigoid (Pg) is an autoimmune subepidermal blistering disease that affects the elderly population. The phenotype can be Bullous Pemphigoid (BP), which primarily involves the skin, or Mucous Membrane Pemphigoid (MMP), which primarily involves mucus membranes. Ocular Cicatricial Pemphigoid (OCP) and Oral Pemphigoid (OP) are subsets of MMP. The known antigens in BP are Bullous Pemphigoid Antigen 1 (BPAG1, also known as BP230), Bullous Pemphigoid Antigen 2 (BPAG2, also known as BP180), and subunits of human integrins α6 and β4. The Human Leukocyte Antigen (HLA) allele HLA-DQβ1*0301 has been reported to be associated with enhanced susceptibility to all of these subsets. Sera of patients with the four subsets are characterized by the presence of anti-Basement Membrane Zone (anti-BMZ) antibodies. In this manuscript, we present a model in which relevant portions of the four different antigens involved in pemphigoid have potential sites that could be presented by an antigen presenting cell (APC) in conjunction with DQβ1*0301 to a T cell receptor to initiate the process that results in anti-BMZ antibody production. Thus, this model provides a hypothetical computer-based mechanism to explain how a single HLA allele can be associated with the production of antibodies to four different antigens that result in four different subsets of a disease with four different clinical profiles and prognoses.
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