Mismatch for the Minor Histocompatibility Antigen HA-2 and GVHD Occurrence in HLA-A*0201-positive Tunisian Recipients of HSCs
ABSTRACT Graft-versus-Host disease (GVHD) has been widely linked to immunogenetic causes such as disparity between the recipient and its HLA geno-identical donor for some Non-HLA antigens called minor histocompatibility antigens (MiHAgs). HA-2 is one of potential human MiHAgs but its effect on the GVHD occurrence remains not clear. In order to examine such association in the Tunisian cohort of HSCs recipients, we performed a retrospective study on patients who received an HLA-identical HSCT between 2000 and 2009. The study was performed on 60 HLA-A2-positive patients who had received a haematopoietic stem cell transplant from an HLA-identical sibling. All patients received cyclosporine A and/or methotrexate for GVHD prophylaxis. HA-2 genotyping assay was performed with SSP-PCR method and HLA-A*0201 positive samples were identified mainly with Luminex HLA-Typing method. Luminex HLA-Typing assay showed that only 53 cases were positives for the HLA-A*0201 allele. Among these cases, only 3 pairs were mismatched for the MiHAg HA-2. Acute GVHD occurred in 01 HA-2-mismatched pair while chronic GVHD was detected in 02 disparate couples. Univariate and multivariate analyses showed that MiHAg HA-2 disparity does not have any significant effect on the occurrence of either acute or chronic GVHD. This last one appeared to be correlated only with the age of patient (adulthood) (p: 0.011, OR: 22.092). Our findings support the previously reported data denying the influence of the HA-2 disparity on the GVHD occurrence after HSCT.
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ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is a procedure in which infusion of hematopoietic stem cells is used to reestablish hematopoietic function in patients with damaged or defective bone marrow or immune systems. Early and late complications following allogeneic HSCT include acute and chronic graft-versus-host disease (GVHD), donor rejection, graft failure, relapse of primary malignancy, conditioning-related toxicity, immunodeficiency and infections. Immunology has a central role in allogeneic hematopoietic cell transplantation. Any appreciation of the immunological mechanism involved in engraftment, GVHD, the development of tolerance, immune reconstitution, and the control of malignancy requires some understanding of the immunologic basis for immune reactions provoked by grafting tissue from one individual to another. In the future it should be possible to learn what gene(s) must be activated and which must be repressed to force stem cells into division without maturation; to engineer a mechanism into the cells that stops proliferation and sets the stage for amplification; to search if there could be a universal donor cell line, neatly packaged and stabilized in sealed vials and distributed by the pharmaceutical industry; to modify the transplanted cells in such a way that they have a proliferative advantage over those of the host and to deliver the lethal blow against the neoplasm, perhaps the cells that are infused will be engineered in such a way as to be able to distinguish between normal host cells and tumor.Immunological investigations 08/2014; 43(8):1-30. DOI:10.3109/08820139.2014.942460 · 1.99 Impact Factor