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- Title
Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity.
- Authors
Arvey, Aaron; Rowe, Michael; Legutki, Joseph Barten; An, Gang; Gollapudi, Anantha; Lei, Anna; Colston, Bill; Putterman, Chaim; Smith, David; Stiles, Janelle; Tarasow, Theodore; Ramamoorthy, Preveen
- Abstract
Background: The immune system undergoes a myriad of changes with age. While it is known that antibody-secreting 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.
- Subjects
PROTEIN microarrays; AGE; CELLULAR aging; HUMORAL immunity; AUTOIMMUNITY; PSYCHONEUROIMMUNOLOGY
- Publication
Immunity & Ageing, 2020, Vol 17, Issue 1, pN.PAG
- ISSN
1742-4933
- Publication type
Article
- DOI
10.1186/s12979-020-00193-x