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Comprehensive Virome-wide Antibody Responses by Systematic Epitope Scanning After Hematopoietic Cell Transplantation

Rachel A. Bender Ignacio, Sayan Dasgupta, Terry Stevens-Ayers, Tomasz Kula, Joshua A. Hill, Stephanie J. Lee, Marco Mielcarek, Ann Duerr, Stephen Elledge and Michael Boeckh

Key Points

  • VirScan highlights both donor and recipient contributions to the viral antibody repertoire, and acquisition of new viral epitopes after HCT

  • Age, CMV serostatus, and receipt of glucocorticoids correlate with recognition of viral epitopes after hematopoietic cell transplantation

Abstract

Further insight into humoral viral immunity after hematopoietic cell transplantation (HCT) could have potential impact on donor selection or monitoring of patients. Currently, estimation of humoral immune recovery is inferred from lymphocyte counts or immunoglobulin levels and does not address vulnerability to specific viral infections. We interrogated the viral antibody repertoire before and after HCT using a novel serosurvey (VirScan) that detects immunoglobulin G responses to 206 viruses. We performed VirScan on cryopreserved serum from pre-HCT and 30, 100, and 365 days after myeloablative HCT from 37 donor-recipient pairs. We applied ecologic metrics (a- and b-diversity) and evaluated predictors of metrics and changes over time. Donor age and donor/recipient CMV serostatus and receipt systemic glucocorticoids were most strongly associated with VirScan metrics at d100. Other clinical characteristics, including pre-HCT treatment and conditioning, did not affect anti-viral repertoire metrics. The recipient repertoire was most similar (pairwise b-diversity) to that of donor at d100, but more similar to pre-HCT self by day 365. Gain or loss of epitopes to common viruses over the year post-HCT differed by donor and recipient pre-HCT serostatus, with highest gains in naïve donors to seropositive recipients for several human herpesviruses and adenoviruses. We used VirScan to highlight contributions of donor and recipient to anti-viral humoral immunity and evaluate longitudinal changes. This work builds a foundation to test whether such systematic profiling could serve as a biomarker of immune reconstitution, predict clinical events after HCT, or help refine selection of optimal donors.

  • Submitted January 25, 2019.
  • Revision received June 11, 2019.
  • Accepted June 4, 2019.