<INTRODUCTION>

Current progress in immunosuppressive therapy has successfully controlled ABO-incompatibility in renal transplantation, although donor specific HLA antibody (DSA) is still insurmountable. Our in vitro experiments have recently demonstrated that anti-blood group A/B antibody binding to endothelial cells could induce “graft accommodation” through up-regulation of complement regulatory proteins (CD55/CD59) and down-regulation of HLA-DR expression, which is supported by the clinical finding that DSA particularly against class II could cause chronic antibody-mediated rejection (AMR), but anti-A/B antibody would not. Furthermore, possible protective effect against chronic AMR in ABO-incompatible renal transplantation (ABO-I) might be suggested.

The purpose of this study was to clarify the potential clinical benefit of ABO-incompatibility in DSA-induced chronic AMR.

<METHODS>

Four hundred and fifty one patients including 122 ABO-I and 329 ABO identical or compatible renal transplantation (ABO-Id/C) between 2005 and 2011 were enrolled in this study. Pre-transplant DSA-positive recipients were excluded. Since 2011, annual screening tests for detecting de novo DSA have been examined in all follow-up recipients. The prevalence of de novo DSA production, proportion of HLA specificity and incidence of biopsy-proven chronic AMR were compared between ABO-I and ABO-Id/C.

<RESULTS>

Between 2011 and 2015, de novo DSA was detected in 60 of 451 patients. There was no significant difference in prevalence of de novo DSA production between ABO-I and ABO-Id/C (9.8% [12/122] vs. 14.6% [48/329]).

Episode biopsy was conducted in 39 patients (8 ABO-I and 31 ABO-Id/C) with de novo DSA prior to manifestation of graft dysfunction. HLA antibody specificity test revealed that proportion of DR-associated de novo DSA was significantly lower in ABO-I compared with ABO-Id/C (8.3% vs. 45.8%, P=0.02). Biopsy-proven subclinical chronic AMR was considerably lower in ABO-I compared with ABO-Id/C (25% [2/8] vs. 54.8% [17/31].

<CONCLUSION>

We found that the incidence of chronic AMR in ABO-I was lower than in ABO-Id/C, probably due to low possibility of de novo anti-DR DSA production, which could be caused by anti-A/B antibody binding-induced down-regulation of HLA-DR expression in graft endothelial cells.

CITATION INFORMATION: Okada M, Watarai Y, Iwasaki K, Futamura K, Hiramitsu T, Tsujita M, Goto N, Narumi S, Kobayashi T. Lower Incidence of DSA-Induced Chronic Antibody-Mediated Rejection in Abo-Incompatible Renal Transplantation. Am J Transplant. 2017;17 (suppl 3).

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