TY - JOUR
T1 - Impact of SIRPα polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation
AU - Garcia-Sanchez, Cynthia
AU - Casillas-Abundis, M. Aurora
AU - Pinelli, David F.
AU - Tambur, Anat R.
AU - Hod-Dvorai, Reut
N1 - Funding Information:
We are grateful for Jar How Lee and One Lambda for providing the primers for SIRPα typing.
Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - CD47
KW - HLA-identical
KW - SIRPα
KW - allorecognition
KW - innate immunity
KW - interstitial inflammation
KW - ischemia-reperfusion injury
KW - kidney (allograft) function/dysfunction
KW - peritubular capillaritis
KW - rejection
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U2 - 10.1111/ctr.14406
DO - 10.1111/ctr.14406
M3 - Article
C2 - 34180101
AN - SCOPUS:85109395468
VL - 35
JO - Clinical Transplantation
JF - Clinical Transplantation
SN - 0902-0063
IS - 9
M1 - e14406
ER -