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Polymorphisms in the Immunoregulatory Genes are Associated with Hematopoietic Recovery and Increased Susceptibility to Bacterial Infections in Patients with Thalassaemia Major Undergoing Matched Related Hematopoietic Stem Cell Transplantation

Shanmugaapriya Sellathamby, Kavitha M. Lakshmi, Marc Busson, Auro Viswabandya, Biju George, Vikram Mathews, Mammen Chandy, Dominique Charron, Rajagopal Krishnamoorthy, Ryad Tamouza, Alok Srivastava
2012 Biology of Blood and Marrow Transplantation  

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In this study, the impact of polymorphisms in the genes of proinflammatory (IL-b, TNF-a, IL-6, IFN-g), antiinflammatory (transforming growth factor [TGF]-b, IL-10, IL-Ra), and other immunoregulatory factors (FcgRIIa, NOS3) along with the conventional risk factors on the rate of hematopoietic recovery and first episodes of bacterial, viral, or invasive fungal infections in 102 patients with b-thalassaemia major who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with
more » ... tively uniform protocols at our center from June 1995 to June 2004 with a minimum follow-up of at least 2 years were studied retrospectively for 180 days after hematopoietic stem cell transplantation (HSCT). Our data show that (1) donor IL-1RN*2/2 (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.17-5.09; P 5 .018) and FCgRIIA 14481G/G genotypes (HR, 3.1; 95% CI, 1.56-6.31; P 5 .001) increased the incidence of bacterial infection; (2) fungal infection was increased in recipients with whose donors had IFN-g 1874T/T genotype (HR, 3.8; 95% CI, 1.08-13.62; P 5 .037); (3) time to neutrophil recovery was shorter in splenectomized patients (HR, 3.1; 95% CI, 1.70-5.64; P \.001), donors without IL-10 -1082A, -819T, and -592A haplotype (HR, 1.6; 95% CI, 1.02-2.39; P 5 .039), and recipients with IFN-g 1874A/A genotype (HR, 1.6; 95% CI, 1.05-2.56; P 5 .029); and (4) time to platelet recovery was shorter in patients with IL-10 -1082A/A genotype (HR, 1.8; 95% CI, 1.14-2.68; P 5 .010) and with donors having TNF-a -308G/G genotypes (HR, 1.8; 95% CI, 1.06-2.93; P 5 .028). These data suggest that outcome after allogeneic stem cell transplantation could be affected by many factors. The mechanisms by which they bring about such impact needs further evaluation.
doi:10.1016/j.bbmt.2012.01.011 pmid:22252124 fatcat:tcwdxyahbzg45bi7oysldetg3e
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Shanmugaapriya Sellathamby, Kavitha M. Lakshmi, Marc Busson, Auro Viswabandya, Biju George, Vikram Mathews, Mammen Chandy, Dominique Charron, Rajagopal Krishnamoorthy, Ryad Tamouza, Alok Srivastava. "Polymorphisms in the Immunoregulatory Genes are Associated with Hematopoietic Recovery and Increased Susceptibility to Bacterial Infections in Patients with Thalassaemia Major Undergoing Matched Related Hematopoietic Stem Cell Transplantation." Biology of Blood and Marrow Transplantation 18.8 (2012) 1219-1226