Complement system in diseases

The impact of complement factor H-related protein gene deletions on kidney transplantation

The paper investigates the impact of CFHR gene deletions on kidney transplant rejection risk and identifies associated SNPs and protein expression changes.

The Fc fragment of soluble IgMs binds C1q to activate the first step of the classical complement pathway, while inhibiting complement-dependent cytotoxicity

This study investigates the binding of IgM Fc fragments to C1q and their role in complement activation and inhibition of cytotoxicity.

Targeting C2 reduces ischemia-reperfusion injury-induced complement activation in preclinical human models

This study shows that targeting C2 reduces complement activation in human kidney ischemia-reperfusion injury models using 2D and 3D in vitro systems.

Tissue Kallikrein 1 cleaves complement factor C3 and activates the alternative complement pathway

This study shows that KLK1 cleaves complement factor C3 and activates the alternative complement pathway in HSCT-TMA, contributing to endothelial injury and renal dysfunction.

Cross-species protection suggests Entamoeba histolytica trogocytosis enables complement resistance through the transfer of negative regulators of complement activation

The paper shows that Entamoeba histolytica uses trogocytosis to acquire and display human complement regulators, enabling resistance to complement lysis even when exposed to mouse serum.

Complement C3aR deletion does not attenuate neurodegeneration in a tauopathy model or alter acute inflammation-induced gene expression changes in the brain

This study shows that deleting C3aR does not reduce neurodegeneration in a tauopathy model or alter gene expression changes during acute inflammation.

Titanium Nanoparticle Regulates Innate Immunity

This paper investigates how titanium nanoparticles regulate innate immunity by suppressing inflammation through interaction with complement C3.

A percolation-type criticality threshold controls immune protein coating of surfaces

The paper identifies a critical threshold in complement activation based on surface density, showing percolation-type behavior in immune responses to materials.

Proof-of-Concept in a Murine Model of Treatment of Thrombotic Thrombocytopenic Purpura Using Engineered Red Blood Cells

This paper demonstrates that engineered red blood cells expressing ADAMTS13 can treat TTP in mice by cleaving vWF under physiological conditions.

When blood needs to flow: The role of the complement system in red blood cell clearance during immune responses

This study shows the complement system actively regulates red blood cell mortality during immune responses to optimize blood flow and tissue perfusion.

A surface lipoprotein on Pasteurella multocida binds complement factor I to promote immune evasion.

This paper identifies PmSLP as a bacterial surface protein that binds complement factor I to enhance immune evasion by cleaving complement components C3b and C4b without cofactors.

Terminal complement complexes with or without C9 potentiate antimicrobial activity against Neisseria gonorrhoeae

This study shows that terminal complement complexes, with or without C9, enhance antimicrobial activity against Neisseria gonorrhoeae, re-sensitizing drug-resistant strains to antibiotics.

Genotoxic chemotherapy impedes complement dependent cytotoxicity via Chk1-mediated CD59 regulation

This study shows genotoxic chemotherapy increases CD59 expression, reducing complement-dependent cytotoxicity and rituximab efficacy in DLBCL via Chk1-mediated regulation.

Granzyme K drives a newly-intentified pathway of complement activation

This study identifies granzyme K as a driver of a novel complement activation pathway independent of classical, lectin, or alternative pathways.

A predominately pulmonary activation of complement in a mouse model of severe COVID-19

This study identifies pulmonary complement activation in a mouse model of severe COVID-19, showing local complement production and its role in lung injury.

Complement receptor C3ar1 deficiency does not alter brain structure or functional connectivity across early life development

This study finds no significant brain structural or functional differences in C3ar1-deficient mice across development, suggesting C3ar1 may not be critical for neurodevelopment.

Complement activation at injury sites drives the phagocytosis of necrotic cell debris and resolution of liver injury

This study shows that complement proteins C1q and C3b promote phagocytosis of necrotic debris by neutrophils, monocytes, and macrophages, which is essential for liver injury resolution.

C1q in non-immune human serum has a non-redundant complement function towards clinical Mycobacterium tuberculosis complex strains

This study shows that C1q from the classical complement pathway, along with MBL from the lectin pathway, recognizes MTBC strains, with C1q playing a key role in complement activation.

Complement Biosensors Identify a Classical Pathway Stimulus in Complement-Mediated Hemolytic Uremic Syndrome

The paper develops complement biosensors to identify classical pathway stimulation in CM-HUS, revealing IgM-driven mechanisms in patients lacking alternative pathway variants.

Thrombospondin-1 inhibits alternative complement pathway activation in vasculitis synergistically to factor H

This study identifies TSP-1 as a FH-independent inhibitor of the alternative complement pathway, showing its role in vasculitis by modulating complement activation and NETosis.

A selective alternative pathway complement inhibitor for treatment of paroxysmal nocturnal hemoglobinuria

This paper introduces SH-01, a novel recombinant protein that selectively inhibits the complement alternative pathway, showing efficacy in preventing PNH-related erythrocyte lysis and reduced infection risk compared to current treatments.

DNA nanostructure-templated antibody complexes provide insights into the geometric requirements of human complement cascade activation

This study uses DNA nanostructures to template IgG antibodies and investigate how IgG valency affects complement activation, revealing that antigen number correlates with complement cleavage and terminal pathway activation.

CUB and Sushi Multiple Domains 1 (CSMD1) opposes the complement cascade in neural tissues

The paper investigates the role of CSMD1 in opposing the complement cascade in neural tissues and links its dysfunction to schizophrenia risk.

C1QA is an invariant biomarker for tissue macrophages

This study identifies C1QA as a consistent biomarker for tissue macrophages and explores its role in anti-microbial pathways.

Spatial and temporal profiling of the complement system uncovered novel functions of the alternative complement pathway in brain development

The paper uses spatial transcriptomics to study complement system development in the brain, revealing distinct roles of the classical and alternative pathways.

High-throughput complement component 4 genomic sequence analysis with C4Investigator

The paper develops C4Investigator, a bioinformatic pipeline for high-throughput analysis of C4 gene variants from genomic data, revealing high poly-allelic variation in the 1000 Genomes Project Dataset.

Pathway-based Rare Variant Burden Analysis Identifies a Role for the Complement System in an Extreme Phenotype of Sepsis with Coagulopathy

The paper identifies rare variants in the complement system associated with severe sepsis with coagulopathy using pathway-based analysis of whole exome sequencing data.

The global carrier frequency and genetic prevalence of Upshaw-Schulman syndrome

The paper estimates the carrier frequency and genetic prevalence of Upshaw-Schulman syndrome using gnomAD data and pathogenic variant analysis.

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

This study shows that complement components C3 and C3aR differentially affect innate anxiety and conditioned fear in mice, linking complement pathways to psychiatric disorder risk.

The Sez6 family inhibits complement at the level of the C3 convertase.

This study shows that Sez6 family members inhibit C3 convertase activity in both classical and alternative complement pathways.