title: Autoantigen complementarity and its contributions to hallmarks of autoimmune disease.
abstract: The question considered is, "What causes the autoimmune response to begin and what causes it to worsen into autoimmune disease?" The theory of autoantigen complementarity posits that the initiating immunogen causing disease is a protein complementary (antisense) to the self-antigen, rather than a response to the native protein. The resulting primary antibody elicits an anti-antibody response or anti-idiotype, consequently producing a disease-inciting autoantibody. Yet, not everyone who developes self-reactive autoantibodies will manifest autoimmune disease. What is apparent is that manifestation of disease is governed by the acquisition of multiple immune-compromising traits that increase susceptibility and drive disease. Taking into account current cellular, molecular, and genetic information, six traits, or 'hallmarks', of autoimmune disease were proposed: (1) Autoreactive cells evade deletion, (2) Presence of asymptomatic autoantibodies, (3) Hyperactivity of Fc-FcR pathway, (4) Susceptibility to environmental impact, (5) Antigenic modifications of self-proteins, (6) Microbial Infections. Presented here is a discussion on how components delineated in the theory of autoantigen complementarity potentially promote the acquisition of multiple 'hallmarks' of disease.
authors.affiliation: UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7155, USA. Electronic address: wfp3@med.unc.edu.
authors.forename: William F
authors.initials: WF
authors.lastname: Pendergraft
authors.affiliation: UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7155, USA.
authors.forename: Anshul K
authors.initials: AK
authors.lastname: Badhwar
authors.affiliation: UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7155, USA.
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Preston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011961:Receptors, Fc / Q000276:immunology; D017386:Sequence Homology, Amino Acid
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D011961:Receptors, Fc
keywords: ANCA; Autoantigen complementarity; Autoimmune disease; Hallmarks; Idiotypic