Complement articles from across Nature Portfolio

IgG3 antibodies have potent effector functions, but are not used as therapeutics and structural data are missing. Here, the authors combine cryoEM and MS to study IgG3-mediated complement activation to provide the first structural insights into IgG3.

Complement proteins and receptors with intracellular activity — the complosome — have emerged as important regulators of physiological processes. In this Review, the authors examine evidence of complosome activity across a variety of cells and tissues, as well as their contributions to human disease and therapeutic potential.

CD59 protects human cells from damage by the MAC immune pore. The authors show how CD59 inhibits MAC, by deflecting pore-forming β-hairpins of complement proteins. As well as how the membrane environment influences the role of CD59 in complement regulation and in host-pathogen interactions.

Right ventricular (RV) failure is clinically crucial, but there is no specific therapy. Here, the authors show that the complement alternative pathway is activated in RV failure and that blockade of the pathway ameliorates RV failure in mice.

Properdin is the only known positive regulator of the human complement system, stabilising the convertase C3 in the alternative pathway of complement activation. Here, the authors report the identification and characterisation of a species-specific properdin inhibitor CirpA, derived from tick saliva.

Two studies show that tau pathology drives the expression of complement molecules that in turn promote the phagocytosis of synapses and neuroinflammation.

Deposition of fibrin in the brain and central nervous system occurs after injury or disease. This process unmasks a conserved cryptic epitope of fibrin that activates microglia; blocking this interaction can limit inflammation and neurotoxicity.

Boireet al. describe a mechanism by which cancer cells can survive and grow in the leptomeninges of the brain by upregulating complement component 3 (C3) to disrupt blood–cerebrospinal fluid barrier function, allowing entry of growth-promoting factors.