Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity
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RESEARCH
Open Access
Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity Aaron Arvey1, Michael Rowe1, Joseph Barten Legutki2 , Gang An1, Anantha Gollapudi2, Anna Lei2, Bill Colston1, Chaim Putterman3,4,5, David Smith2, Janelle Stiles2, Theodore Tarasow1* and Preveen Ramamoorthy2*
Abstract Background: The immune system undergoes a myriad of changes with age. While it is known that antibodysecreting plasma and long-lived memory B cells change with age, it remains unclear how the binding profile of the circulating antibody repertoire is impacted. Results: To understand humoral immunity changes with respect to age, we characterized serum antibody binding to high density peptide microarrays in a diverse cohort of 1675 donors. We discovered thousands of peptides that bind antibodies in age-dependent fashion, many of which contain di-serine motifs. Peptide binding profiles were aggregated into an “immune age” by a machine learning regression model that was highly correlated with chronological age. Applying this regression model to previously-unobserved donors, we found that a donor’s predicted immune age is longitudinally consistent over years, suggesting it could be a robust long-term biomarker of humoral immune ageing. Finally, we assayed serum from donors with autoimmune disease and found a significant association between “accelerated immune ageing” and autoimmune disease activity. Conclusions: The circulating antibody repertoire has increased binding to thousands of di-serine peptide containing peptides in older donors, which can be represented as an immune age. Increased immune age is associated with autoimmune disease, acute inflammatory disease severity, and may be a broadly relevant biomarker of immune function in health, disease, and therapeutic intervention. Keywords: Antibody binding profile, Immune age, Auto-immune disease, Machine learning, Immunosenescence, Antibody response, Peptide library
Background Ageing is associated with broad decline in organ function and increased risk for chronic disease. The immune system undergoes dramatic changes associated with age, including decreased immune response, loss of immune memory, and increased chronic inflammation. These * Correspondence: [email protected]; [email protected] 1 iCarbonX 2424 Camino Ramon, Suite 125, San Ramon, CA 94583, USA 2 HealthTell, 145 S. 79th St., Chandler, AZ 85226, USA Full list of author information is available at the end of the article
immune dysfunctions manifest as re-activation of latent infection, decreased tumor immunosurveillance, and age-associated chronic immunopathologies [1–4]. Both adaptive and innate immune mechanisms are impaired, as evidenced by antigen-independent decreases in cellular proliferation and function [5, 6], migration [7], T-cell receptor diversity [8], antibody secretion [9], phagocytic abilities [10], cytotoxicity [11], and broad dysregulation of cytokines and chemokines [6, 12].
© The Author(s). 2020 Open Access This article is licensed under a C
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