Association of HLA-G Low Expressor Genotype with Severe Acute Graft-Versus-Host Disease after Sibling Bone Marrow Transplantation (original) (raw)
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Biologia, 2020
Graft-versus-host disease (GVHD) in its acute (aGVHD) and chronic (cGVHD) form remains one of the most serious complications of allogeneic haematopoietic stem cell transplantation (allo-HSCT). There are several risk factors known to be associated with GVHD development. Some reports suggest that certain human leukocyte antigen (HLA) variants may influence the incidence of GVHD. The aim of our study was to analyse possible association between individual HLA alleles and the occurrence of aGVHD and cGVHD in patients following allo-HSCT from HLA-identical sibling donors. We have retrospectively reviewed medical records of 96 patients who received a transplant in the years 1994-2008. Cumulative incidence of acute GVHD was 31.3% and that of chronic GVHD was 26.0%. Recipients carrying the HLA-A*01,-DRB1*03 and-DQB1*03 alleles showed a statistically significantly lower incidence of aGVHD. Furthermore, the HLA-DQB1*06 allele was associated with a higher incidence of cGVHD. Each of these alleles was confirmed by logistic regression analysis as an independent factor with impact on GVHD development. Our results support findings of authors showing an association between certain HLA variants and GVHD appearance. However, other authors assume that there is no convincing evidence for such an association. Therefore, when taking into account limitations of our study design and the significant inconsistency in the results of the previous reports, a careful approach in judgement is required. To conclude, in our view, the prognostic value of individual HLA variants for GVHD development in a setting of HLA-identical allo-HSCT does not seem to be of great clinical relevance. Keywords Haematopoietic stem cell transplantation. Human leukocyte antigens. Graft-versus-host disease Abbreviations aGVHD Acute graft-versus-host disease allo-HSCT Allogeneic haematopoietic stem cell transplantation cGVHD Chronic graft-versus-host disease CI Confidence interval CsA Cyclosporin A HLA Human leukocyte antigens HSCT Haematopoietic stem cell transplantation miHA Minor histocompatibility antigens MTX Methotrexate
Experimental and Clinical Transplantation, 2020
HLA-E is located on the nonclassical major histocompatibility complex class I and acts as the ligand for natural killer cells. Consequently, it has a main role in the regulation of innate immune responses by involving cell identification by natural killer cells. Differences in expression levels among HLA-E alleles have been suggested to affect transplant outcomes. In this study, we evaluated the effects of different HLA-E genotypes on allogeneic hema-topoietic stem cell transplant in southern Iran. Materials and Methods: We investigated 200 patients (donors and recipients) who underwent allogeneic hematopoietic stem-cell transplant and 100 normal participants (control group) in a case-control study. Detection of HLA-E polymorphisms was performed using a sequence-specific primer polymerase chain reaction method. Results: Statistical analyses indicated that genotypes in the transplant group were not distributed in accordance with Hardy-Weinberg equilibrium (χ 2 = 76.56; P < .001), whereas genotypes in the control group were distributed in accordance with Hardy-Weinberg equilibrium (χ 2 = 0.39; P = .53). No significant differences were observed in cumulative incidence of acute (P = .76; hazard ratio = 0.80; 95% confidence interval, 0.19-3.31) and chronic (P = .75, hazard ratio = 0.048; 95% confidence interval, 0.00) graft-versus-host disease in recipients harboring HLA-E*0103 allele compared with those homozygous for the HLA-E*0101 allele. The HLA-E*0103 allele showed a trend toward lower cumulative incidence of relapse compared with the homozygous HLA-E*0101 genotype (8% vs 21.5%; P = .37; hazard ratio = 2.50; 95% confidence interval, 0.32-19.20).
Bone Marrow Transplantation, 2004
A total of 110 patients (71 adults and 39 children) who received allogeneic haematopoietic stem cell transplantation from HLA-matched sibling donors were studied for the incidence of acute graft-versus-host disease (aGvHD) in relation to IFN-gamma gene microsatellite polymorphism. A strong tendency was observed towards the lower incidence of grades II-IV aGvHD in patients having an IFN-gamma 2/2 genotype as compared to the recipients with other IFN-gamma genotypes (0.12 vs 0.33, P ¼ 0.06). This relationship was independent of the intensity of conditioning regimen and diagnosis. IFN-gamma polymorphic features, together with other clinical and biological factors (patient's age, donor-recipient gender, diagnosis, conditioning regimen, transplant material and GvHD prophylaxis), were subjected to multivariate analysis for aGvHD manifestation in order to exclude indirect association of the IFN-gamma 2/2 genotype. In multivariate analysis, myeloablative therapy (OR ¼ 11.462, P ¼ 0.013), recipient age (OR ¼ 4.896, P ¼ 0.009) and lack of IFN-gamma 2/2 genotype (OR ¼ 4.311, P ¼ 0.048) were found to significantly contribute to the development of grade II-IV aGvHD, while type of GvHD prophylaxis showed less-strong influence (OR ¼ 2.963, P ¼ 0.066). Thus, it appeared that the IFN-gamma 2/2 genotype constituted an independent and protective factor associated with a decreased risk of grade II-IV aGvHD. However, this genotype was not found to be associated with the risk of cGvHD or survival.
Bone Marrow Transplantation, 2003
We evaluated the outcome of 63 children given haematopoietic stem cell transplantation from unrelated donors (URD-HSCT) prospectively selected using DNA highresolution typing of both HLA class I and class II loci. Thirty patient/donor pairs (48%) were fully matched. Among the others, HSCT was performed in the presence of one (n ¼ 22), two (n ¼ 9), or three (n ¼ 2) HLA disparities. Patients had either malignant (n ¼ 46) or non-malignant (n ¼ 17) disease. In all cases, graft-versushost disease (GVHD) prophylaxis consisted of cyclosporin A, short-term methotrexate and pretransplant antithymocyte globulin. The probability of haematopoietic recovery at day 100 was 97%. Two patients experienced primary graft failure. The cumulative probability of grades III-IV acute GVHD and of extensive chronic GVHD equalled 8 and 14%, respectively. A total of 12 patients died of transplant-related complications. The probability of transplant-related mortality (TRM) at 100 and 180 days was 10 and 15%, respectively, whereas the cumulative incidence of TRM was 22%. The probability of GVHD-related mortality equalled 6% at 2.5 years. The overall and disease-free survival rates were 67 and 65%, respectively. URD-HSCT with donor selection based on high-resolution HLA typing is associated with low incidence of both severe acute GVHD and graft failure. The observed outcome is comparable to that of children transplanted from HLA-identical siblings.
Impact of highly conserved HLA haplotype on acute graft-versus-host disease
Blood, 2010
Although the effects of human leukocyte antigen (HLA) locus matching on clinical outcome in unrelated hematopoietic stem cell transplantations have been characterized, the biologic implications of HLA haplotypes have not been defined. We demonstrated the genetic fixity of Japanese conserved extended haplotypes by multi–single nucleotide polymorphism analysis in 1810 Japanese donor-recipient pairs matching with HLA-A, -B, -C, -DRB1, and -DQB1 alleles. Three major Japanese conserved extended haplotypes (named HP-P1, HP-P2, and HP-P3) were essentially completely conserved at least in the 3.3-Mb HLA region from HLA-A to -DPB1, and extended far beyond HLA-A. The risk of acute graft-versus-host disease (GVHD) of these HLA haplotypes was assessed with multivariate Cox regression in 712 patients transplanted from HLA fully (HLA-A, B, C, DRB1, DQB1, and DPB1) matched unrelated donors. HP-P2 itself reduced the risk of grade 2 to 4 acute GVHD (hazard ratio [HR] = 0.63; P = .032 compared with H...