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

Signal-regulatory protein alpha (SIRP alpha), 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 SIRP alpha 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 SIRP alpha in a cohort of 55 HLA-identical, biologically-related, donor-recipient pairs. 69% of pairs were SIRP alpha identical. No significant differences were found between donor-recipient SIRP alpha-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 SIRP alpha-mismatched group. Unexpectedly, graft-versus-host (GVH) SIRP alpha-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 SIRP alpha-mismatched recipients and the higher rates of GF in GVH SIRP alpha-mismatched pairs represent a potential role for SIRP alpha in linking innate immunity and alloimmune rejection requires further investigation in larger cohorts.