Immunogenetic analysis of post-schistosomal liver fibrosis.
Schistosomiasis is a major endemic parasitic disease in the world. In China, we have identified two major genes related to the severity of liver fibrosis, one an HLA class II gene, and the other the IL-13 gene. The frequency of the HLA-DRB5*0101 allele and that of the IL-13 promoter A/A (IL-13P- A/A) genotype were elevated in fibrotic patients, although the two genes are located on different chromosomes, chromosomes 6p and 5q, respectively. Subjects with both genotypes had odds ratios (OR=24.5) much higher than the sum of the ratios for each individual genotype (OR=5.1, 95% confidence interval 1.3-24.7 for HLA-DRB5*0101, OR=3.1 95% CI 1.5-6.5 for IL-13P- A/A). Although we have not yet characterized the functional difference between HLA-DRB5*0101 and other alleles, peripheral blood mononuclear cells from IL-13PA/A donors produced much higher amount of mRNA than IL-13PA/B 24 h after the stimulation with PHA. Those findings strongly suggest that the pathogenic Th2 response directly influences the prognosis of post-schistosomal liver fibrosis.
Hirayama
Kenji
K
Department of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. hiraken@net-nagasaki-u.ac.jp
D000818:Animals; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059847:HLA-DRB5 Chains; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012549:Schistosoma japonicum; D012554:Schistosomiasis japonica / Q000150:complications / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D006684:HLA-DR Antigens; D059847:HLA-DRB5 Chains; D018793:Interleukin-13