Anti-C4B monoclonal antibody, clone 10-12

The complement system is an innate immunity effector mechanism; its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by several pathogens evolved under strong selective pressure in primates, with selection acting on residues at the contact interface with microbial/viral proteins. Positively selected sites in CFH and C4BPA account for the human specificity of gonococcal infection. Bacterial interactors, evolved adaptively as well, with selected sites located at interaction surfaces with primate complement proteins. These results epitomize the expectation under a genetic conflict scenario whereby the host's and the pathogen's genes evolve within binding avoidance-binding seeking dynamics. In silico mutagenesis and protein-protein docking analyses supported this by showing that positively selected sites, both in the host's and in the pathogen's interacting partner, modulate binding.

Epidemiological studies have indicated that both maternal bacterial and viral infections during pregnancy increase the risk of schizophrenia among offspring, but to date there is not clear explanation for this increased risk. Previously, the decreased C4b-binding protein (C4BP), a potent circulating soluble inhibitor of the classical and lectin pathways of complement, was reported to be associated with risk of schizophrenia. Here, we analyzed 4 common single nucleotide polymorphisms (SNPs) of C4BPB and 5 SNPs of C4BPA in a group of 556 schizophrenia patients and a matched group of 610 healthy controls to see if the genes C4BPB and C4BPA, which encode C4BP, may confer a susceptibility to schizophrenia. Comparing the genotype and allele frequencies of those SNPs between cases and controls, we found no association between the C4BPB/C4BPA variants and schizophrenia. Our results provided preliminary evidence that C4BPB/C4BPA may not confer susceptibility to schizophrenia among Han Chinese. Further genetic studies from large-scale population are required to obtain more conclusive results. (c) 2015 Elsevier Ireland Ltd. All rights reserved.