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.

Keywords:

• Haematopoietic Stem Cells Transplantation
• Graft-vs-Host disease
• Minor histocompatibility antigens
• HA-2
• HLA-A*0201
• Tunisian population

ACKNOWLEDGMENTS

We thank all technicians from the National Blood Transfusion Centre and from the National Bone Marrow Transplantation Centre of Tunis for their valuable technical assistance. We are so grateful to our Italian colleagues from the department of Regenerative Medicine, Organ and Tissue Transplantation Immunology, Ospedale Maggiore Policlinico di Milano and from Lagitre s.r.l, Italy. This work was supported by the Tunisian Ministry for Higher education, Scientific Research and technology; and the Tunisian Ministry of Public Health.

ELECTRONIC-DATABASE INFORMATION

Accession numbers and URLs for data in this article are as follows:

• GenBank: http://www.ncbi.nlm.nih.gov/GenBank/ (HA-2 Gene ID: 64005)

• EnsemblGene: http://www.ensembl.org/ (HA-2 Ensembl Gene ID: ENSG00000136286).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.