Natural IgG Autoantibodies Are Abundant and Ubiquitous in Human Sera, and Their Number Is Influenced By Age, Gender, and Disease

TLDR

Self‑reactive IgG autoantibodies in human sera are generally viewed as a breakdown of central tolerance and a warning of autoimmune disease. The authors propose that these autoantibodies evolved as an adaptive debris‑clearance mechanism, explaining their diagnostic value in neurodegenerative diseases. They profiled serum from 166 individuals using human protein microarrays to quantify and characterize IgG autoantibody abundance and specificity. The study found that IgG autoantibodies are abundant—thousands per serum—bind antigens throughout the body, vary with age, gender, and disease, are individual‑specific and stable over time, and are conserved in rats and swine, implying an important physiological role.

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.