Anti-TNFSF8 Monoclonal antibody, clone SN264 [PE]

Tumor necrosis factors (TNFs) are a group of cytokines that play critical roles in regulating a diverse range of physiological processes in vertebrates. TNFs function by activating a large number of structurally related receptors, leading to TNF mediated biological processes which are evolutionarily conserved. Fish have a much diversified TNF family, partly due to the whole genome duplication events which have occurred in this lineage, providing an excellent model to investigate the neo- and sub-functionalised properties of TNF superfamily. Fish possess most of the TNFs and receptors found in mammals and also some homologues exclusively present in fish. It seems that TNFSF4 (OX40), TNFSF7 (CD27) and TNFSF8 (CD30) and their cognate receptors are absent in teleosts. It has been shown that fish viruses are able to produce TNFR homologues to establish infection by manipulating the host immune system. Understanding the roles of TNFSFs in fish immune defence and the pathogenesis of fish diseases will provide insights into the functions of TNFSFs from an evolutionary perspective and better strategies for improving fish health and welfare in aquaculture. This review summarises recent advances in the study offish TNF biology and focuses on the molecular properties and immunological functions of the TNF and TNFR superfamily.

Background. Type 1 reactions (T1R) affect a considerable proportion of patients with leprosy. In those with T1R, the host immune response pathologically overcompensates for the actual infectious threat, resulting in nerve damage and permanent disability. Based on the results of a genome-wide association study of leprosy per se, we investigated the TNFSF15 chromosomal region for a possible contribution to susceptibility to T1R. Methods. We performed a high-resolution association scan of the TNFSF15 locus to evaluate the association with T1R in 2 geographically and ethnically distinct populations: a family-based sample from Vietnam and a case-control sample from Brazil, comprising a total of 1768 subjects. Results. In the Vietnamese sample, 47 single-nucleotide polymorphisms (SNPs) overlapping TNFSF15 and the adjacent TNFSF8 gene were associated with T1R but not with leprosy. Of the 47 SNPs, 39 were cis-expression quantitative trait loci (cis-eQTL) for TNFSF8 including SNPs located within the TNFSF15 gene. In the Brazilian sample, 18 of these cis-eQTL SNPs overlapping the TNFSF8 gene were validated for association with T1R. Conclusions. Taken together, these results indicate TNFSF8 and not TNFSF15 as an important T1R susceptibility gene. Our data support the need for infection genetics to go beyond genes for pathogen control to explore genes involved in a commensurate host response.