Contribution of TNF-alpha and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation.
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.
Takahashi
H
H
First Department of Internal Medicine, College of Biochemical Technology, Niigata University School of Medicine, Japan.
Furukawa
T
T
Hashimoto
S
S
Suzuki
N
N
Kuroha
T
T
Yamazaki
F
F
Inano
K
K
Takahashi
M
M
Aizawa
Y
Y
Koike
T
T
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10