Rat Anti-Mouse FCGR2A Heterohybridoma [3.5H3]

Influenza remains an important threat for human health, despite the extensive study of influenza viruses and the production of effective vaccines. In contrast to virus genetics determinants, host genetic factors with clinical impact remained unexplored until recently. The association between three single nucleotide polymorphisms (SNPs) and influenza outcome in a European population was investigated in the present study. All samples were collected during the influenza A(H1N1)pdm09 post-pandemic period 2010-11 and a sufficient number of severe and fatal cases was included. Host genomic DNA was isolated from pharyngeal samples of 110 patients from northern Greece with severe (n = 59) or mild (n = 51) influenza A(H1N1)pdm09 disease, at baseline, and the genotype of CD55 rs2564978, C1QBP rs3786054 and FCGR2A rs1801274 SNPs was investigated. Our findings suggest a relationship between the two complement-related SNPs, namely, the rare TT genotype of CD55 and the rare AA genotype of C1QBP with increased death risk. No significant differences were observed for FCGR2A genotypes neither with fatality nor disease severity. Additional large-scale genetic association studies are necessary for the identification of reliable host genetic risk factors associated with influenza A(H1N1)pdm09 outcome. Prophylactic intervention of additional high-risk populations, according to their genetic profile, will be a key achievement for the fight against influenza viruses.

Purpose Cetuximab, a chimeric immunoglobulin G1 ( IgG1) anti-epidermal growth factor receptor ( EGFR) monoclonal antibody ( mAb), has shown efficacy in 10% of patients with metastatic colorectal cancer ( CRC). Recent studies demonstrate antibody-dependent cell-mediated cytotoxicity ( ADCC) is one of the modes of action for rituximab and trastuzumab. Fragment c ( Fc)portion of IgG1 mAb has shown to induce ADCC. Fragment c gamma receptors ( Fc gamma R) play an important role in initiating ADCC. Studies have shown that two IgG Fc gamma R polymorphisms ( FCGR2A-H131R and FCGR3A-V158F) independently predict response to rituximab in patients with follicular lymphoma. We tested the hypothesis of whether these two polymorphisms are associated with clinical outcome in metastatic CRC patients treated with single-agent cetuximab. Patients and Methods Thirty-nine metastatic CRC patients were enrolled onto the ImClone0144 trial. Using an allele-specific polymerase chain reaction ( PCR)-based method, gene polymorphisms of FCGA2A-H131R and FCGA3A-V158F were assessed from genomic DNA extracted from peripheral blood samples. Results FCGR2A-H131R and FCGR3A-V158F polymorphisms were independently associated with progression-free survival ( PFS; P = .037 and.055, respectively; log-rank test). Combined analysis of these two polymorphisms showed that patients with the favorable genotypes ( FCGR2A, any histidine allele, and FCGR3A, any phenylalanine allele) showed a median PFS of 3.7 months ( 95% CI, 2.4 to 4.4 months), whereas patients with any two unfavorable genotypes ( FCGR2A arginine/arginine or valine/valine) had a PFS of 1.1 months ( 95% CI, 1.0 to 1.4 months; P = .004; log-rank test). Conclusion Our preliminary data suggest that these two polymorphisms may be useful molecular markers to predict clinical outcome in metastatic CRC patients treated with cetuximab and that they may indicate a role of ADCC of cetuximab.