Genomic collision at the LIMS-1 locus increases risk of cellular mediated allograft rejection in heart transplanted recipients

Hum Immunol. 2024 Dec 5;86(1):111189. doi: 10.1016/j.humimm.2024.111189. Online ahead of print.

Abstract

Genomic collision at the LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) locus between donor and heart recipient was examined for the association with diagnosis of acute cellular or antibody-mediated allograft rejection, ACR or ABMR, respectively. In this single center retrospective study, 129 heart transplanted patients and donors were genotyped for the LIMS1 rs893403 variant, where the G-allele is in almost complete linkage disequilibrium with a loss of function deletion. A total of 14 cases with genomic collision (recipient genotype GG and donor genotype AA/AG) were identified. After a median follow-up time of 723 days, the multivariate adjusted hazard ratio for ACR of 1.64 (95 % CI 0.66-4.1) indicated that genomic collision indeed was a risk factor, while the risk of ABMR was less affected by genotype. Although statistically not significant, due to low power, this study indicates that LIMS1 is a minor histocompatibility antigen in heart transplantation, associated with allograft rejection.

Keywords: Allograft rejection; Genetics; Heart transplantation; LIMS1; Minor histocompatibility antigen.