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

• Published in: Biology of blood and marrow transplantation 2012-08, Vol.18 (8), p.1219-1226
• Main Authors: Sellathamby, Shanmugaapriya, Lakshmi, Kavitha M, Busson, Marc, Viswabandya, Auro, George, Biju, Mathews, Vikram, Chandy, Mammen, Charron, Dominique, Krishnamoorthy, Rajagopal, Tamouza, Ryad, Srivastava, Alok
• Format: Article
• Language: English
• Subjects: Adolescent; Bacterial Infections - etiology; Bacterial Infections - genetics; beta-Thalassemia - genetics; beta-Thalassemia - surgery; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Hematology, Oncology and Palliative Medicine; Hematopoietic recovery; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; HSC transplantation; Humans; Immunogenetic factors; Immunomodulation - genetics; Infant; Infection; Male; Polymorphism, Single Nucleotide; Thalassaemia major; Transplantation, Homologous; Treatment Outcome; Young Adult
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2012.01.011

In this study, the impact of polymorphisms in the genes of proinflammatory (IL-β, TNF-α, IL-6, IFN-γ), anti-inflammatory (transforming growth factor [TGF]-β, IL-10, IL-Ra), and other immunoregulatory factors (FcγRIIa, 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 β-thalassaemia major who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with relatively 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 = .018) and FCγRIIA +4481G/G genotypes (HR, 3.1; 95% CI, 1.56-6.31; P = .001) increased the incidence of bacterial infection; (2) fungal infection was increased in recipients with whose donors had IFN-γ +874T/T genotype (HR, 3.8; 95% CI, 1.08-13.62; P = .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 = .039), and recipients with IFN-γ +874A/A genotype (HR, 1.6; 95% CI, 1.05-2.56; P  = .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 = .010) and with donors having TNF-α -308G/G genotypes (HR, 1.8; 95% CI, 1.06-2.93; P = .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.