title: Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease.
abstract: The presence of self-reactive IgG autoantibodies in human sera is largely thought to represent a breakdown in central tolerance and is typically regarded as a harbinger of autoimmune pathology. In the present study, immune-response profiling of human serum from 166 individuals via human protein microarrays demonstrates that IgG autoantibodies are abundant in all human serum, usually numbering in the thousands. These IgG autoantibodies bind to human antigens from organs and tissues all over the body and their serum diversity is strongly influenced by age, gender, and the presence of specific diseases. We also found that serum IgG autoantibody profiles are unique to an individual and remarkably stable over time. Similar profiles exist in rat and swine, suggesting conservation of this immunological feature among mammals. The number, diversity, and apparent evolutionary conservation of autoantibody profiles suggest that IgG autoantibodies have some important, as yet unrecognized, physiological function. We propose that IgG autoantibodies have evolved as an adaptive mechanism for debris-clearance, a function consistent with their apparent utility as diagnostic indicators of disease as already established for Alzheimer's and Parkinson's diseases.
authors.affiliation: Biomarker Discovery Center, New Jersey Institute for Successful Aging, University of Medicine and Dentistry of New Jersey, Stratford, NJ, USA. nagelero@umdnj.edu
authors.forename: Eric P
authors.initials: EP
authors.lastname: Nagele
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.forename: Nimish K
authors.initials: NK
authors.lastname: Acharya
authors.forename: Cassandra
authors.initials: C
authors.lastname: DeMarshall
authors.forename: Mary C
authors.initials: MC
authors.lastname: Kosciuk
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nagele
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D051381:Rats; D012737:Sex Factors; D013552:Swine; D054875:Ubiquitination
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G