title: The molecular basis for the presence of two autoimmune diseases occurring simultaneously--preliminary observations based on computer analysis.
abstract: Specific Human Leukocyte Antigen Class II (HLA II) molecules associated with pemphigus vulgaris (PV), mucous membraine pemphigoid (MMP), and mixed connective tissue disease (MCTD) may react with multiple T cell epitopes within desmoglein 3 (Dsg 3), bullous pemphigoid antigen 2 (BPAG 2), and 70 kDa polypeptide small nuclear ribonucleoproteins (snRNP70) in autoantibody production. We report a group of patients with simultaneous occurrences of PV with MCTD, and MMP with MCTD. In one patient group, we performed serological studies to show presence of antibodies to Dsg 3, Dsg 1, and snRNP70 simultaneously. In the second group, we performed serological studies to show presence of antibodies to BPAG 1, BPAG 2, β4 integrin, and snRNP70 simultaneously. In both groups, HLA II genes were analyzed and the observations were consistent with previously described associations with PV, MMP, and MCTD. It is possible that HLA-DQβ1*0301 allele, present in 10 of 17 patients and DRβ1*04 in some of the others, may have the ability to bind to several relevant T cell epitopes in the snRNP70 molecule. We have utilized a computer model to demonstrate that HLA II-restricted T cell epitopes present within the known autoantigens may be capable of eliciting an immune response. While other explanations and mechanisms exist, the authors suggest that epitope spreading may be one possible mechanism, amongst others, that may result in the simultaneous presence of two separate pathogenic autoantibodies.
authors: Center for Blistering Diseases, Boston, Massachusetts 02120, USA.
authors: Labib R
authors: LR
authors: Zakka
authors: Pedro A
authors: PA
authors: Reche
authors: A Razzaque
authors: AR
authors: Ahmed
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D019295:Computational Biology / Q000379:methods; D003598:Cytoskeletal Proteins / Q000276:immunology; D051183:Desmoglein 1 / Q000276:immunology; D051184:Desmoglein 3 / Q000276:immunology; D000071821:Dystonin; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D008947:Mixed Connective Tissue Disease / Q000150:complications / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000276:immunology; D024041:Non-Fibrillar Collagens / Q000276:immunology; D010390:Pemphigoid, Benign Mucous Membrane / Q000150:complications / Q000235:genetics / Q000276:immunology; D010392:Pemphigus / Q000150:complications / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D051183:Desmoglein 1; D051184:Desmoglein 3; D000071821:Dystonin; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human