Chief Scientific Officer CDI Labs Baltimore, Maryland, United States
Abstract Text:
Introduction:
Recent advances in high-throughput synthetic biology tools enable massively multiplexed serologic profiling of antigen-specific antibody repertoires by proteome microarray and phage-display immunoprecipitation sequencing (PhIP-Seq). However, little remains known about the impact of individual genetics on these global profiles or repertoire stability across time.
Methods:
In order to determine the impact of genetics and time on anti-viral and anti-self antibody repertoires, we obtained serum samples from twenty pairs of monozygotic twins (TwinsUK) at an initial timepoint and again after at least a decade of ageing. We ran all eighty samples on three platforms: human proteome microarrays (HuProt, >21,000 full-length proteins, CDI Labs), human proteome PhIP-Seq (HuScan, >700,000 49-mer peptides, CDI Labs Canada), and pan-viral PhIP-Seq (VirScan, >480,000 62-mer peptides, CDI Labs Canada). IgG hits across each platform were tallied in relation to negative controls.
Results:
Strikingly, all patients on all platforms had highly-correlated-hits across their paired samples before and after 10+ years of ageing (median Jaccard similarity 0.49, 0.41, 0.33 for VirScan IgG, HuScan IgG, and HuProt IgG, respectively). Patient profiles poorly correlated with their identical twin on all platforms (0.14, 0.05, 0.08, respectively) although this was significantly higher than between unrelated individuals (0.10, 0.02, 0.07, respectively; Mann-Whitney p < 0.0001 for all comparisons).
Conclusion:
Immunologic memory has long been known to remain stable for years against certain individual antigens; herein we demonstrate that this applies across the majority of known viral and self-antigens and manifests uniquely even among genetically identical individuals.
