GZMB and PRF1 mRNA expression and donor genotypes and their associations with post-transplant complications in allogeneic hematopoietic stem cell transplant recipients

Graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection are serious complications after allogeneic hematopoietic stem cell transplantation (HSCT) and NK cells are involved in their pathogenesis. As granzyme B (GzmB) and perforin are markers of cytotoxicity, we examined polymorphism and expression of GzmB and perforin genes in the context of HSCT outcome. A number of 247 patients and 117 donors were genotyped for GZMB rs8192917 and PRF1 rs885822 variants, and GZMB and PRF1 mRNA expression as well as serum levels were assessed 30 and 90 days post-transplantation. Chronic GvHD (cGvHD) and CMV infection were associated with donor GZMB rs8192917 TT genotype (p < 0.0001) while donor PRF1 rs885822 GG was predominant in patients with acute GvHD (p < 0.0001). GZMB expression decreased post-transplantation in recipients with cGvHD (p = 0.0237) while patients with CMV exhibited higher expression of GZMB (p = 0.0027) and PRF1 (p = 0.0035) on day 90 in comparison to recipients without complications. Strong correlations were observed between the expression of GZMB and PRF1 (p < 0.0001, R = 0.767) and between IFNG (interferon-γ) and GZMB (p = 0.0007, R = 0.69) and PRF1 (p = 0.0013, R = 0.67). Serum GzmB concentration decreased significantly over time in patients (p < 0.0001). These results suggest that GZMB and PRF1 genotypes and expression may be potential markers of post-transplant complications and have roles in cGvHD and CMV pathogenesis.