title: 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.
authors.affiliation: Etablissement Français du Sang, Ile de France, HLA Laboratory, Créteil, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Delbos
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Barhoumi
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Cabanne
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Beckerich
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Robin
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Rabah
authors.initials: R
authors.lastname: Redjoul
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Safae
authors.initials: S
authors.lastname: Astati
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Andréa
authors.initials: A
authors.lastname: Toma
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.affiliation: Etablissement Français du Sang, Ile de France, HLA Laboratory, Créteil, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ansart-Pirenne
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: Etablissement Français du Sang, Ile de France, HLA Laboratory, Créteil, France; IMRB, University Paris Est Créteil, INSERM U955, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.affiliation: Department of Hematology, AP-HP, Hôpital Henri Mondor, DHU Virus-Immunity-Cancer, Créteil, France; IMRB, University Paris Est Créteil, INSERM U955, Créteil, France; Center for Clinical Investigation in Biotherapy, Créteil, France. Electronic address: sebastien.maury@hmn.aphp.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
mesh_terms: D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D006681:HLA-D Antigens / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods*; D008297:Male; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006681:HLA-D Antigens
keywords: Anti-HLA antibodies; Graft-versus-host disease; Risk factor analysis