Contribution of TNF-α and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 26; no. 12; pp. 1317 - 1323
• Main Authors: TAKAHASHI, H, FURUKAWA, T, HASHIMOTO, S, SUZUKI, N, KUROHA, T, YAMAZAKI, F, INANO, K, TAKAHASHI, M, AIZAWA, Y, KOIKE, T
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.12.2000
• Subjects: Acute Disease; Adolescent; Adult; Alleles; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Autoimmune diseases; Biological and medical sciences; Blood cells; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Chronic conditions; Chronic Disease; Cytokines; Gene polymorphism; Graft rejection; Graft versus host disease; Graft vs Host Disease - genetics; Graft-versus-host reaction; Grafts; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Interleukin 10; Interleukin-10 - genetics; Medical sciences; Microsatellite Repeats; Middle Aged; Multivariate Analysis; Polymorphism, Genetic; Risk Factors; Stem cell transplantation; Stem cells; Systemic lupus erythematosus; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous - adverse effects; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-α; Human; Immunopathology; Stem cell; Cytokine; Hematopoietic cell; Homograft; Graft versus host reaction; Malignant hemopathy; Genetic determinism; Treatment; Gene; Risk factor; Interleukin 10; Graft; Genetics; Complication; Tumor necrosis factor α; Polymorphism
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1702724

Some cytokines are believed to play a role in the development of acute and chronic GVHD after allo-hematopoietic stem cell transplantation. It has been reported that TNF-alpha and IL-10 gene polymorphisms are associated with the production of those cytokines and the development of graft failure after organ transplantation and systemic lupus erythematosus. We examined whether TNF-alpha and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis of aGVHD and cGVHD, respectively. We analyzed the gene polymorphisms derived from pre- and post-transplant blood cells. Donor-derived TNF2 allele (A) was more frequently detected in patients with aGVHD III/IV than those aGVHD 0-II (2/6 vs 2/56) (P = 0.04). The donors of the patients with cGVHD more frequently possessed a greater number of alleles (allele 13 or more which contain 26 or more CA repeats) in IL-10.G than those without (13/26 vs 5/28) (P = 0.02), and the patients with cGVHD had more CA repeats in donor-derived IL-10.G than those without (mean = 25.2 vs 23.4) (P = 0.01). Donor-derived TNF-308 and IL-10.G alleles may contribute to severe aGVHD and cGVHD, respectively, and will help us distinguish those patients at high risk for GVHD.