Anti-PDCD1 monoclonal antibody, clone RMP1-30

Purpose. Programmed cell death 1 (PD-1) is an important immune checkpoint of T cells response and plays a critical role in chronic hepatitis B virus (HBV) infection. The purpose of this study was to investigate the associations between PD-1 polymorphisms and susceptibility and disease progression of chronic HBV infection. Methods. In this case-control study, 299 cases with chronic HBV infection comprised of 99 asymptomatic carriers (ASCs), 96 patients with chronic hepatitis B (CHB), and 104 patients with HBV-related acute on chronic liver failure (HBV-ACLF) were enrolled. A total of 82 spontaneously recovered subjects were enrolled as controls. Three single nucleotide polymorphisms (SNPs) of PD-1, including PD-1.1, PD-1.5, and PD-1.9 were analyzed by Sequenom MassARRAY system. Results. The frequency of PD1.1 AA genotype was found to be significantly higher in the chronic HBV infection group compared with spontaneously recovered group (27.1% vs. 18.3%, P=0.049), and the frequency of PD-1.5 TT genotype and allele T were both significantly lower in chronic HBV infection group compared with spontaneously recovered group (genotype: 4.7% vs. 9.8%, P=0.04; allele: 22.1% vs. 30.5%, P=0.025). The frequency of haplotype GTC (PD-1.1 G, PD-1.5 T, PD-1.9 C) was significantly lower in patients with chronic HBV infection compared with spontaneous recovery cases (P=0.026). No significant differences were found in the genotype distributions of the three SNPs among the different clinical types of chronic HBV infection (P>0.53). Conclusions. Our results suggest that PD1 polymorphisms are associated with susceptibility to chronic HBV infection in the Chinese population. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

Objective: To elucidate the genetic predisposition of Rasmussen syndrome (RS). Methods: In 29 Japanese patients, we examined the genome sequences of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed cell-death 1 (PDCD1), and T-bet (TBX21) genes by direct sequencing, and evaluated the significance of SNPs (single nucleotide polymorphism) by comparison with Hap Map data. Results: In all patients, no disease-causative mutations were found in CTLA4, PDCD1, and T-bet. However, rs231775 SNP in exon 1 of CTLA4 showed significant positive genotypic (p = 0.0363) and allelic associations (p = 0.0137) with onset of RS compared with Japanese controls, as did rs231779 SNP in intron 1 of CTLA4 (p = 0.0467 and 0.0188, respectively). Also, rs2227982 SNP in exon 5 of PDCD1 showed significant positive genotypic and allelic associations with RS (p = 0.0145 and 0.0114, respectively). Poor cognitive outcome (IQ below 50) was found in 0% of wild type (C/C), 9% of heterologous (C/T) and 25% of homologous (T/T) genotype of rs2227982. Quadriplegia was found only in homologous (T/T) genotype, and hemiplegia was in heterologous (C/T) and homologous (T/T) genotype of rs2227982. No association between SNPs of T-bet and RS onset was found. Regarding SNPs in promoter regions (rs4794067 and rs17250932) of T-bet, however, IQ below 50 was found in 19% of wild type (TIT) and 0% of heterologous (TIC) genotype of rs4794067, and in 19% of wild type (TIT) and 0% of heterologous (TIC) genotype of rs17250932. Quadriplegic patients were found only in wild-type patients (rs4794067 and rs17250932). Conclusions: We identified three SNPs (rs231775, rs231779, rs2227982) as some of the SNPs associated with onset of Japanese RS. We need further studies in other populations to confirm these genetic predispositions in RS. (C) 2013 Elsevier B.V. All rights reserved.