Impact of SIRPα polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation

Cynthia Garcia-Sanchez*, M. Aurora Casillas-Abundis, David F. Pinelli, Anat R. Tambur, Reut Hod-Dvorai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Signal-regulatory protein α (SIRPα), a polymorphic inhibitory membrane-bound receptor, and its ligand CD47 have recently been implicated in the modulation of innate immune allorecognition in murine models. Here, we investigate the potential impact of SIRPα donor-recipient mismatches on graft outcomes in human kidney transplantation. To eliminate the specific role of HLA-matching in alloresponse, we genotyped the two most common variants of SIRPα in a cohort of 55 HLA-identical, biologically-related, donor-recipient pairs. 69% of pairs were SIRPα identical. No significant differences were found between donor-recipient SIRPα-mismatch status and T cell-mediated rejection/borderline changes (25.8% vs. 25%) or slow graft function (15.8% vs. 17.6%). A trend towards more graft failure (GF) (23.5% vs. 5.3%, P =.06), interstitial inflammation (50% vs. 23%, P =.06) and significant changes in peritubular capillaritis (ptc) (25% vs. 0%, P =.02) were observed in the SIRPα-mismatched group. Unexpectedly, graft-versus-host (GVH) SIRPα-mismatched pairs exhibited higher rates of GF and tubulitis (38% vs. 5%, P =.031 and.61 ±.88 vs. 0, P =.019; respectively). Whether the higher prevalence of ptc in SIRPα-mismatched recipients and the higher rates of GF in GVH SIRPα-mismatched pairs represent a potential role for SIRPα in linking innate immunity and alloimmune rejection requires further investigation in larger cohorts.

Original languageEnglish (US)
JournalClinical Transplantation
DOIs
StateAccepted/In press - 2021

Keywords

  • allorecognition
  • CD47
  • HLA-identical
  • innate immunity
  • interstitial inflammation
  • ischemia-reperfusion injury
  • kidney (allograft) function/dysfunction
  • peritubular capillaritis
  • rejection
  • SIRPα

ASJC Scopus subject areas

  • Transplantation

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