Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease
Open accessAbstract
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.
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Age-related changes in the microbiota toward gram-negative and endotoxigenic bacteria are known to induce cellular senescence and apoptosis in endothelial cells and damage to intestinal epithelial cells and gut-associated lymphoid tissues, thereby disrupting intestinal epithelial barrier integrity.
“Furthermore, age-related changes in the microbiota toward gram-negative and endotoxigenic bacteria are known to induce cellular senescence and apoptosis in endothelial cells and damage to intestinal epithelial cells and gut-associated lymphoid tissues thereby disrupting the intestinal epithelial barrier integrity (50–54).”
From Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice (2021) · cites this paper as [51]
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References 35 · Cited by 309
- Authors
- Nagele, E. P., Han, M., Acharya, N. K., DeMarshall, C., Kosciuk, M. C., & Nagele, R. G.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Nagele, Robert G.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-02
- Volume
- 8
- Issue
- 4
- Pages
- e60726
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3617628
- OpenAlex
- W2002697968
- Cited by
- 309
- References
- 35
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 21 · 2023: 27 · 2022: 22 · 2021: 28 · 2020: 34 · 2019: 33 · 2018: 25 · 2017: 28 · 2016: 23 · 2015: 18 · 2014: 13 · 2013: 7
- FWCI
- 16.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rowan Digitals Works (Rowan University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- New Jersey Health Foundation
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IgG autoantibodies, self-reactive antibodies, human serum, autoantibody profiling, central tolerance, age and gender effects, interindividual variability, cross-species conservation, debris removal, Alzheimer's disease, Parkinson's disease, biomarkers
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Animals, Antigens, Autoantibodies, Autoimmune Diseases, Female, Humans, Immunoglobulin G, Male, Middle Aged, Sex Factors, Swine, Protein Array Analysis, Rats, Ubiquitination
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