P049 Anti-angiotensin II Type-1 receptor antibodies in failed chimerism after hematopoietic stem cell transplantation

Abstract

Aim A critical role of the renin-angiotensin system has been increasingly recognized in hematopoiesis. Anti-Angiotensin II Type-1 Receptor (AT1R) antibodies have been shown to mimic the effect of AT1R ligand, angiotensin II in solid organ transplantation while little is known about their impact in hematopoietic stem cell transplantation (HSCT). We tested anti-AT1R antibodies to evaluate the impact of antibodies against non-HLA factors on engraftment outcomes after HSCT. Methods A total of 357 post-transplant serum samples from 205 patients were collected at the time of chimerism engraftment testing between November 2014 and July 2015. Of those, serial samples were obtained from 79 patients. All post-transplant samples were tested for both HLA and AT1R antibodies, and their results were evaluated in relation to engraftment outcomes. Patients ( n = 178) after exclusion criteria applied were classified into three groups based on thresholds of both chimerism donor DNA 85% and follow-up month 3 (Group 1: mean donor DNA 55% with mean follow-up months 28; Group 2: mean donor DNA >99% with mean follow-up months 19; Group 3: mean donor DNA >99% with mean follow-up months 1.3). Results Post-transplant AT1R antibodies were detectable in 16% of unrelated transplant patients and 10% of related transplant patients. Among three groups classified based on donor DNA% and follow-up months, significantly higher levels of AT1R antibodies were observed in only Group 1 with failing chimerism (Mann–Whitney P = 0.005 [Groups 1 vs. 2] and P = 0.03 [Groups 1 vs. 3]) with no correlation with HLA antibodies. Moreover, this Group 1 had significantly delayed neutrophil recovery ( P = 0.02). Analysis of individual anti-AT1R development patterns showed that patients with increasing levels of AT1R antibodies during engraftment monitoring had significantly higher chance of developing acute GVHD ( P = 0.03). Conclusions The present study showed distinctive characteristics of AT1R antibodies in failed donor chimerism and acute GVHD. Further study is warranted for a value of accessing AT1R antibodies for both early and long-term engraftment monitoring and for identification of potential therapeutic targets in HSCT.