Anti-TNFSF18 monoclonal antibody, clone 200228 [Biotin]

Human genetic variation is a determinant of recovery from acute hepatitis C virus (HCV) infection; however, to date, single-nucleotide polymorphisms (SNPs) in only a limited number of genes have been studied with respect to HCV clearance. We determined whether SNPs in 112 selected immune response genes are important for HCV clearance, by genotyping 1536 SNPs in a cohort of 343 persons with natural HCV clearance and 547 persons with HCV persistence. PLINK (version 1.05) and Haploview (version 4.1) software packages were used to perform association, permutation, and haplotype analyses stratified by African American and European American race. Of the 1536 SNPs tested, 1426 (92.8%) were successfully genotyped. In African Americans, we identified 18 SNPs located in 11 gene regions that were associated with HCV infection outcome (empirical P value, < .01). In European Americans, there were 20 SNPs located in 8 gene regions associated with HCV infection outcome. Four of the gene regions studied (TNFSF18, TANK, HAVCR1, and IL18BP) contained SNPs for which the empirical P value was <.01 in both of the race groups. In this large-scale analysis of 1426 genotyped SNPs in 112 candidate genes, we identified 4 gene regions that are likely candidates for a role in HCV clearance or persistence in both African Americans and European Americans.

Mercury is a ubiquitous environmental toxicant which bioaccumulates and has many biological effects, including detrimental effects on the nervous and immune systems. Because mercury can cross the placenta and concentrates in the fetal compartment, the developing fetus is particularly vulnerable. We hypothesize that developmental exposure to mercury will cause immunological changes, leading to an increased susceptibility to, or exacerbation of, immune disorders later in life. To better understand these changes, we exposed pregnant female mice to low doses of mercury for a short duration and examined the genetic effects related to immune function in the adult offspring. Pregnant BALB/c mice were exposed to mercury (200 mu g/kg HgCl2 in PBS by subcutaneous injection) or vehicle control every other day from gestation day 5 to 15. Offspring remained with the dam until weaning and were euthanized at 8 weeks of age with no further exposures to mercury. Splenic RNA was isolated and gene expression changes examined by microarray in a non-random subset of samples and changes confirmed by quantitative PCR. Epigenetic changes were also examined in terms of miRNA levels in the spleen. Although male and female offspring were exposed to mercury in the same in utero environment, the effects on expression of immune-related genes and immune-regulatory epigenetic signals were different dependent upon the sex of the offspring with males, but not females, displaying up-regulation at least two-fold of arginase, interferon-gamma, STAT1, vitronectin, and TNFSF18. Epigenetic changes in miRNA levels were differentially expressed in males and females with in utero mercury exposure; miR-191-5p was decreased in males, while miR-1188-3p was increased in females. These gene expression and gene regulation changes modulate the baseline immune response and may impact risks for autoimmunity later in life.