AI Article Synopsis
- The study examines the impact of certain non-HLA genetic variations (polymorphisms) on the survival rates of patients undergoing hematopoietic stem cell transplantation (HSCT) from unrelated donors, focusing on specific genes like TNFa, IL-10, and IL-1.
- Researchers analyzed genetic variants in 131 patient-donor pairs and found that specific polymorphisms in TNFd and IL-10 correlated with lower survival rates, particularly in patients with certain genotypes.
- The findings suggest that genetic testing for these polymorphisms, alongside HLA matching, could help predict outcomes for patients receiving unrelated HSCT, potentially leading to better personalized treatment strategies.
Article Abstract
Background: Non-HLA immunogenetic polymorphisms may influence outcome of hematopoietic stem cell transplantation (HSCT). In this study, we have determined the role of TNFa, TNFd, IL-10, IL-1, IL-1Ra, and IL-4R polymorphisms in patients transplanted with HSC of an unrelated donor.
Methods: The allelic variants of four SNPs (IL-10-1082, IL-1beta-511, IL-4R-3223, IL-4R-1902) and four microsatellites (TNFa, TNFd, IL-10-1064, IL-1Ra) were determined in 131 unrelated patient/donor pairs typed for HLA-A/B/C/DR/DQ (four digits).
Results: The allelic distribution of the polymorphisms was similar to that previously reported in Caucasoid populations. Patient and donor TNFd and patient IL-10-1064 polymorphisms correlated with mortality in univariate analysis. Patients with TNFd1/d2/d3 genotypes had 3-year survival rates of 65%. A gradual decrease in survival rates was observed for patients with TNFd3/d3 genotypes (50%, p=n.s.), TNFd4 (46%, P=0.08), and TNFd5 (33%, P=0.03). A multivariate analysis of 10/10 matched patients revealed that the following patient genotypes correlated with lower survival: TNFd3/d3 (RR 4.08, P=0.026) TNFd4 (RR 3.78, P=0.032) and TNFd5 (RR 6.69, P=0.021) all compared to TNFd1/d2/d3 genotypes. Patient IL-10 (12, 14, 15) microsatellite alleles correlated with lower 3-year survival (28%) when compared to IL-10 (<12) (56%, P=0.052) and to Il-10 (13) alleles (60%, P=0.0023). In multivariate analysis this correlation remained significant only in recipients of HSCT of 10/10 HLA matched donors (RR=2.96, P=0.038).
Conclusion: The data demonstrate a significant correlation of the TNFd and IL-10-1064 microsatellite polymorphisms with mortality after unrelated HSCT. They support the hypothesis that simple genomic tests, in addition to precise HLA matching, may contribute to determine prognosis in patients undergoing unrelated HSCT.
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Article Synopsis
- The study examines the impact of certain non-HLA genetic variations (polymorphisms) on the survival rates of patients undergoing hematopoietic stem cell transplantation (HSCT) from unrelated donors, focusing on specific genes like TNFa, IL-10, and IL-1.
- Researchers analyzed genetic variants in 131 patient-donor pairs and found that specific polymorphisms in TNFd and IL-10 correlated with lower survival rates, particularly in patients with certain genotypes.
- The findings suggest that genetic testing for these polymorphisms, alongside HLA matching, could help predict outcomes for patients receiving unrelated HSCT, potentially leading to better personalized treatment strategies.
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