TY - JOUR
T1 - Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity
AU - Arvey, Aaron
AU - Rowe, Michael
AU - Legutki, Joseph Barten
AU - An, Gang
AU - Gollapudi, Anantha
AU - Lei, Anna
AU - Colston, Bill
AU - Putterman, Chaim
AU - Smith, David
AU - Stiles, Janelle
AU - Tarasow, Theodore
AU - Ramamoorthy, Preveen
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/10/6
Y1 - 2020/10/6
N2 - 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.
AB - 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.
KW - Antibody binding profile
KW - Antibody response
KW - Auto-immune disease
KW - Immune age
KW - Immunosenescence
KW - Machine learning
KW - Peptide library
UR - http://www.scopus.com/inward/record.url?scp=85092492983&partnerID=8YFLogxK
U2 - 10.1186/s12979-020-00193-x
DO - 10.1186/s12979-020-00193-x
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C2 - 33042204
AN - SCOPUS:85092492983
SN - 1742-4933
VL - 17
JO - Immunity and Ageing
JF - Immunity and Ageing
IS - 1
M1 - 28
ER -