Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity

Immunity & Ageing

Chaim Putterman¹  Anantha Gollapudi²  Anna Lei²  David Smith²  Janelle Stiles²  Preveen Ramamoorthy²  Joseph Barten Legutki²  Michael Rowe³  Theodore Tarasow³  Aaron Arvey³  Bill Colston³  Gang An³ 

[1] Albert Einstein College of Medicine, Division of Rheumatology, Forchheimer 701N, 1300 Morris Park Ave, 10461, Bronx, NY, USA;Azrieli Faculty of Medicine, Bar-Ilan University, Zefat, Israel;Research Institute, Galilee Medical Center, Nahariya, Israel;HealthTell, 145 S. 79th St., 85226, Chandler, AZ, USA;iCarbonX 2424 Camino Ramon, Suite 125, 94583, San Ramon, CA, USA;

关键词: Antibody binding profile;    Immune age;    Auto-immune disease;    Machine learning;    Immunosenescence;    Antibody response;    Peptide library;   

DOI  :  10.1186/s12979-020-00193-x

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsTo 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.ConclusionsThe 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.

【 授权许可】

CC BY