Donor Immunization Against Human Leukocyte Class II Antigens is a Risk Factor for Graft-versus-Host Disease

Abstract

The sensitization to HLA antigens is caused mainly by pregnancy and transfusions; however, anti-HLA antibodies also may be detected in nulliparous females and nontransfused males, and thus specifically in hematopoietic stem cell transplantation (HSCT) donors. In such cases, the impact on HSCT outcome is known only for platelet transfusion refractoriness. This study addresses the impact on graft-versus-host disease (GVHD) of anti-HLA antibodies detected in voluntary unrelated donors. Among 100 donor/recipient (D/R) pairs, 33 and 82 showed at least 1 HLA class I and class II mismatch, respectively. Because class II mismatches were more frequent, we focused our detection on anti-class II antibodies, using the Luminex assay. Among 82 HLA class II mismatched D/R pairs, 26 donors (32%) had at least 1 anti-HLA class II antibody detected in peripheral blood. Recipients of a graft from an anti-class II immunized donor had a higher cumulative incidence for a first episode of either acute or chronic GVHD (2- year cumulative incidence, 88% versus 67%; P = .03), which was confirmed in multivariate analysis (hazard ratio, 1.7; P = .04). In particular, according to the National Institutes of Health classification scheme, the cumulative incidence of chronic GVHD was higher in recipients of immunized donors (multivariate hazard ratio, 2.5; P = .02). Identifying specificities of anti-class II antibodies revealed that 13 of 26 alloimmunized donors had recipient-specific antibodies, directed mainly against mismatched HLA-DPB1 alleles. Donor-derived anti-HLA antibodies could be detected in recipients up to at least 6 months post-HSCT, supporting their association with chronic GVHD. Donor immunization against foreign HLA antigens is a new parameter to predict the occurrence of GVHD after HSCT from HLA-mismatched unrelated donors.

BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

“…At present, there is no formal testing of donors for the presence of antibodies reactive with HLA mismatches of the recipient; recipient‐specific antibodies (RSA). One single‐centre study has described an increased incidence of either aGVHD or cGVHD in patients transplanted with donors who were sensitized to HLA class II, predominantly mismatched HLA‐DPB1 alleles (Delbos et al., 2016). It has been reported that donor‐derived HLA antibodies can be detected post‐transplant in patients transplanted with donors that are positive for HLA antibodies which suggests they could impact on engraftment in HLA‐mismatched transplants (Taniguchi et al., 2012).…”

Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease

“…Indeed, in unrelated donor-recipient settings, the presence of anti-HLA-DPB1 antibodies was clinically relevant with respect to development of transplant-related complications, including cGvHD. The outcome of having HLA antibodies in voluntary unrelated donors was analyzed by Delbos et al ( 47 ). They observed a significantly higher cumulative incidence of cGvHD in recipients transplanted with anti-HLA class II immunized donors, directed mainly against HLA-DPB1 alleles.…”

Major Histocompatibility Complex and Hematopoietic Stem Cell Transplantation: Beyond the Classical HLA Polymorphism

“…Theoretically, recipient-specific anti-HLA antibodies also might affect the development of GvHD [ 22 ]. In a recent study, Delbos et al evaluated 82 HLA class II mismatched unrelated transplant donor–recipient pairs [ 76 ]. In this cohort, 26 donors (32%) had at least one anti-HLA class II antibody in peripheral blood.…”