Do FY antigens act as minor histocompatibility antigens in the graft-versus-host disease paradigm after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation?

FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.

Evidence that erythrocyte DARC-positive phenotype can affect the GVHD occurrence after HLA-identical sibling HSCT.

Chemokine receptors are very important players in the pathogenesis of GVHD. The aim of this study is to test the hypothesis that the lack of expression of the DARC receptor on erythrocytes can affect the GVHD incidence. A total of 105 recipients and their 105 respective sibling donors of HSCs were enrolled in this study. All patients were evaluated for acute and chronic GVHD. The DARC genotyping assay was performed using the SSP-PCR method. The case-control analyses showed that the donor DARC 146G allele and T(-46)G(146) haplotype, coding for the FY2 version of DARC, are very significant in the GVHD paradigm because they are associated with the incidence of acute effects of this outcome in recipients (p=0.007, χ²=7.200). It seems that this version of DARC receptor is a powerful facilitator of chemokine transcytosis and subsequently leukocyte migration into GVHD target organs.