Mismatch in SIRPα, a regulatory protein in innate immunity, is associated with chronic GVHD in hematopoietic stem cell transplantation

Rima M. Saliba, Uri Greenbaum, Qing Ma, Samer A. Srour, Yudith Carmazzi, Liang Li, Betul Oran, Michael Moller, Janet Wood, Stefan O. Ciurea, Piyanuch Kongtim, Gabriela Rondon, David Partlow, Dan Li, Katayoun Rezvani, Elizabeth J. Shpall, Kai Cao, Richard E. Champlin, Jun Zou

Research output: Contribution to journalArticlepeer-review

Abstract

Recent compelling evidence showed that innate immune effector cells could recognize allogeneic grafts and prime an adaptive immune response. Signal regulatory protein a (SIRPα) is an immunoglobulin superfamily receptor that is expressed on myeloid cells; the interaction between SIRPα and its ubiquitously expressed ligand CD47 elicits an inhibitory signal that suppresses macrophage phagocytic function. Additional studies showed that donor-recipient mismatch in SIRPα variants might activate monocytic allorecognition, possibly as the result of non-self SIRPα-CD47 interaction. However, the frequency of SIRPα variation and its role in hematopoietic stem cell transplantation (HSCT) remains unexplored. We studied 350 patients with acute myeloid leukemia/myelodysplastic syndrome who underwent HLA-matched related HSCT and found that SIRPα allelic mismatches were present in 39% of transplantation pairs. SIRPα variant mismatch was associated with a significantly higher rate of chronic graft-versus-host disease (GVHD; hazard ratio [HR], 1.5; P = .03), especially de novo chronic GVHD (HR, 2.0; P = .01), after adjusting for other predictors. Those with mismatched SIRPα had a lower relapse rate (HR, 0.6; P = .05) and significantly longer relapse-free survival (RFS; HR, 0.6; P = .04). Notably, the effect of SIRPα variant mismatch on relapse protection was most pronounced early after HSCT and in patients who were not in remission at HSCT (cumulative incidence, 73% vs 54%; HR, 0.5; P = .01). These findings show that SIRPα variant mismatch is associated with HSCT outcomes, possibly owing to innate allorecognition. SIRPα variant matching could provide valuable information for donor selection and risk stratification in HSCT.

Original languageEnglish
Pages (from-to)3407-3417
Number of pages11
JournalBlood advances
Volume5
Issue number17
DOIs
StatePublished - 14 Sep 2021
Externally publishedYes

Fingerprint

Dive into the research topics of 'Mismatch in SIRPα, a regulatory protein in innate immunity, is associated with chronic GVHD in hematopoietic stem cell transplantation'. Together they form a unique fingerprint.

Cite this