Inherited and acquired dysregulation of the complement alternative pathway plays an important role in multiple renal diseases. In recent years, the identification of disease-causing mutations and genetic variants in complement regulatory proteins has contributed significantly to our knowledge of the pathogenesis of complement associated glomerulopathies. In these diseases defective complement c...

From the implications of the complement system in a large number of diseases, an urgent need for therapeutics effecting reduced complement activity in vivo has emerged. In this study we report the design of a novel class of enzymes of human origin that obliterate functional complement by a noninhibitory, catalytic mechanism. Combining the framework of human C3 and the enzymatic mechanism of cob...

The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice...

An attempt was made to characterize the mechanism of complement resistance operating in a virulent avian Escherichia coli isolate. Using flow cytometry to detect antibody to C3, we found that there was significantly more antibody bound to a complement-sensitive mutant of this wild type than to the parent organism, suggesting that more C3 subunits were bound to the wild type. Neither the wild ty...

The complement system is part of the innate immune response responsible for removing pathogens and cellular debris, in addition to helping to refine CNS neuronal connections via microglia-mediated pruning of inappropriate synapses during brain development. However, less is known about the role of complement during normal aging. Here, we studied the role of the central complement component, C3, ...

Long-term kidney graft survival is affected by different variables including donor condition, ischemia-reperfusion injury, and graft rejection during the transplantation process. The complement system is an important mediator of renal ischemia-reperfusion injury and in rejecting allografts. However, donor complement C3 seems to be crucial in renal transplantation-related injury as renal injury ...

The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Serum levels of the third and fourth complement components (C3, C4) and complement function (CH50) were examined in this prospective, observational study. Associations between their expression and dise...

Complement C3 is the central component of the human complement system. It is ~186 kDa in size, consisting of an α-chain (~110 kDa) and a β-chain (~75 kDa) that are connected by cysteine bridges. C3 in its native form is inactive. Cleavage of C3 into C3b (~177 kDa) and C3a (~9 kDa) is a crucial step in the complement activation cascade, which can be initiated by one or more of the three distinct...

Complement C3 levels were significantly elevated in subjects with metabolic syndrome compared to the control population (139.95±9.59, 102.12±6.65; p<0.001). Significant difference was also noted in women with metabolic syndrome compared to men with metabolic syndrome (p<0.001).Complement C3 correlated significantly with waist circumference, BMI and total count. C3 also correlated with TC, LDL, ...

Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably ...