Study of 156 dengue patients shows distinct complement signatures by disease severity, with soluble CR1 emerging as an independent early predictor of severe outcomes. #Dengue #Immunology #ComplementSystem #Biomarkers #GlobalHealth #Science buff.ly/da4fIQb
New study shows deleting FHR1 reduces atherosclerosis, inflammation, and plaque formation in mice—revealing a novel immune-lipid axis in cardiovascular disease.
#Atherosclerosis #CardioScience #Immunology #ComplementSystem #TranslationalResearch buff.ly/QEVu3ct
C5aR inhibitors precisely target the core inflammatory pathway, enabling steroid-sparing therapy and opening a new era for immune and inflammatory disease treatment.
doi.org/10.59717/j.x...
#complementsystem #precisionmedicine
New research reveals systemic complement activation, specially elevated Factor B (Bb), is tightly linked to reduced choroidal thickness in advanced nnAMD. #AMD #Ophthalmology #ComplementSystem #Biomarkers #MedTwitter #SciComm #ResearchNews buff.ly/WQP6t8H
🔗 Explore CPX-6502 (tinyurl.com/wm9vz558) via the @emblebi Complex Portal - mapping all biologically functional protein complexes.
#GlobalPNHAwarenessDay #PNH #RareDisease #GPIAnchors #ComplementSystem #GpiGnT #ComplexPortal #EMBLEBI
Recap
The #complementsystem plays a crucial role in chronic inflammation, tissue damage & microvascular clotting in #longCOVID. @virusesimmunity.bsky.social et al indicates that complement activation, which is significantly heightened during acute #COVID persists for months or even years
The complement cascade can be initiated by three distinct pathways: the classical, lectin, and alternative pathways. The classical and lectin pathways are triggered when recognition molecules bind to structures such as antibody complexes and carbohydrates on pathogen surfaces, leading to the activation of their associated proteases C1s/C1r and MASP-1/2. These proteases cleave C4 and C2, generating the C3 convertase (C4b2b), which then processes C3 into the anaphylatoxin C3a and the opsonin C3b. Accumulation of C3b induces the formation of the C5 convertase, which cleaves C5 into C5a and C5b. The subsequent interaction of C5b with C6, C7, C8, and C9 leads to the assembly of a lytic pore, known as the terminal complement complex (TCC). The alternative pathway is initiated when factor B (FB) interacts either with water-hydrolyzed C3, C3(H2O), or with deposited C3b to form the C3(H2O)Bb or C3bBb C3 convertases following factor D (FD) cleavage. These proteases, and in particular, the surface-bound and properdin/factor P–stabilized (FP-stabilized) C3bBbP C3 convertase act as an amplification loop for complement, generating most of the activated C3 fragments regardless of the initiating pathway.
SARS-CoV-2 infection triggers activation of the complement cascade through direct interaction with viral components or virus-specific antibodies, typically resolving once the infection is cleared. However, in patients with long COVID, this activation may persist, potentially contributing to ongoing symptoms. Several proposed mechanisms of long COVID can directly activate the complement system. For example, antiherpesvirus antibodies, likely the result of herpesvirus reactivation, or autoantibodies may drive activation via the classical pathway. Insertion of TCC in the endothelial cell wall causes activation and cell damage, causing the release of TSP1 and vWF. TSP1 promotes formation of monocyte-platelet aggregates, while vWF release — coupled with reduced levels of ADAMTS13, the metalloproteinase responsible for processing vWF multimers — leads to the accumulation of large or ultralarge vWF multimers on the endothelial surface. This, in turn, promotes platelet recruitment and thrombus formation. Additionally, vWF multimers on the endothelium, along with properdin and P selectin on activated platelets, can trap C3b, fueling complement activation via the amplification loop of the alternative pathway. Uncontrolled complement activation in the vasculature leads to red blood cell lysis, causing the release of heme and activation of the alternative pathway. Finally, tissue damage resulting from acute COVID-19, autoimmunity, or viral antigen reservoirs may all contribute to the persistent complement activation observed in patients with long COVID.
In this Review @virusesimmunity.bsky.social et al examine the evidence linking #complementsystem dysregulation to LC & explore its potential role in driving disease pathology.
@jci-insight.bsky.social
insight.jci.org/articles/vie...
#Medsky🧪 #IDsky #immunosky #publichealth Recent studies suggest that dysregulation of the #complementsystem, a key component of the innate immune response, may contribute to the pathogenesis of #longCOVID, particularly in connection with #coagulation, #inflammation & #vascularinjury.
New discovery: FHR1, a complement system protein, plays a surprising role in helping macrophages clear dead cells (efferocytosis). #FHR1 #Immunology #Macrophages #Proteomics #Biotech #ComplementSystem #SingleCell
buff.ly/KkCkG9e
New insights into AMD: A recent study maps the retinal sialome and finds reduced sialic acid at the Bruch's membrane–choroid interface in AMD eyes—potentially impacting complement regulation via factor H (FH). #AMD #Ophthalmology #ComplementSystem buff.ly/jvrGu4F
First #ClusterAnalysis, then #GWAS for #MajorDepression within each subgroup:
#Olfactory genes emerge only in females with ⬇️ #Neuroticism, ⬇️ #BodyFat, & ⬆️ #EducationLevel; while #ComplementSystem genes only in females with the opposite, risk pattern; see our paper:
www.nature.com/articles/s41...
Interesting insight:
C3 glomerulopathy: a kidney disease mediated by alternative pathway deregulation.
#C3G #nephrology #kidney #complementsystem
www.frontiersin.org/journals/nep...
