An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease

Armin Rashidi, Adam Herman, Antonio L.C. Gomes, Jonathan U. Peled, Robert R. Jenq, Daniel G. Brereton, Christopher Staley, Bruce R. Blazar, Daniel J. Weisdorf

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal. In multivariable analysis of data from 613 allogeneic haematopoietic cell transplant recipients, peri-engraftment presence of O. splanchnicus was associated with ~50% lower risk for grade II–IV aGVHD (hazard ratio 0·53, 95% confidence interval 0·28–1·00, P = 0·05). O. splanchnicus may protect rs4415345G individuals against aGVHD.

Original languageEnglish (US)
Pages (from-to)926-930
Number of pages5
JournalBritish journal of haematology
Volume189
Issue number5
DOIs
StatePublished - Jun 1 2020

Bibliographical note

Funding Information:
Armin Rashidi was supported by an American Cancer Society Institutional Research Grant from the University of Minnesota and an American Society of Blood and Marrow Transplantation Young Investigator Award. This research was also supported by NHLBI NIH Award K08HL143189, MSKCC Cancer Center Core Grant P30 CA008748, the Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, the Sawiris Foundation, the Society of Memorial Sloan Kettering Cancer Center, MSKCC Cancer Systems Immunology Pilot Grant, Empire Clinical Research Investigator Program and Seres Therapeutics.

Publisher Copyright:
© 2020 British Society for Haematology and John Wiley & Sons Ltd

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • graft-versus-host disease
  • microbiota
  • odoribacter
  • paneth cell
  • polymorphism

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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