China
Africa
Explore chapters and articles related to this topic
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Helminths have also evolved novel means to avoid complement-mediated damage. Trichinella spiralis, for instance, causes the disease trichinosis. Certain developmental stages of this nematode, notably the adult, which lives in the small intestine, and the encysted larvae, surviving in mammalian striated muscle cells, express calreticulin on their surfaces and secrete it into the surrounding environment. This protein can bind to and inhibit the activity of C1q, the first component in the mammalian classical complement pathway. By inactivating C1q, T. spiralis thus suppresses various complement effector functions, including chemotaxis, cell lysis and inflammation.
Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
The complement system plays a key role in lupus pathophysiology, demonstrating consumption by way of reduced complement levels during disease flares. Either a genetic complement deficiency or a functional defect (i.e., antibodies targeting) in C1q, the initiator of the classical pathway and an opsonin, can lead to SLE. C1q not only is an opsonin but is also involved in removal of apoptotic cells without assembly of an inflammasome. Hence, any defect in C1q leading to decreased clearance of apoptotic cells can result in immune dysregulation. Other complements of the classical pathway including C1r, C1s, C4, and C2 have also been implicated, but to a lesser extent than C1q. Mutations in complement inhibitors such as FH and CD46 have been linked to lupus nephritis. Similarly, by amplifying the effect of C1q-driven immune complexes in kidneys, antibodies to C1q have become a predictive marker for lupus nephritis.39
Specific Host Restance: The Effector Mechanisms
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
C1 consists of three parts: C1q, C1r, and C1s. There is only one C1q in each C1 molecule, but there are two each of C1r and C1s. The C1q part is composed of six subunits with the extended ends tied together in a “stalk” and six globular “heads.” the Fc receptors that bind to constant regions of the antibody molecules (Figure 9.3B). The binding of C1q to the antibody molecules triggers an internal rearrangement in one of the C1r molecules to expose its active site. The activated C1r then cleaves the C1s molecule, exposing its active site. Active C1s is a serine protease.
Systematic analysis of the varied designs of 819 therapeutic antibodies and Fc fusion proteins assigned international nonproprietary names
Published in mAbs, 2022
Pharmacologic properties of immunoglobulins depend very much on their Fc region. Interaction with C1q initiates activation of complement. Binding to various Fc receptors on leucocytes induces antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cell-mediated phagocytosis (ADCP). Binding to the FcRn receptor is responsible for the comparatively long half-life of IgG. For many years, scientists have investigated the structures involved in binding to these various ligands, with the aim of modifying the natural properties of antibodies either to enhance (e.g., to improve killing of tumor cells, or to extend half-life) or to reduce (e.g., to avoid unwanted side effects).11–14 As a result, many therapeutic antibodies and Fc fusion proteins have Fc regions which have been altered compared with wild-type immunoglobulins.
Association of serum mannose-binding lectin, anti-phospholipase A2 receptor antibody and renal outcomes in idiopathic membranous nephropathy and atypical membranous nephropathy: a single center retrospective cohort study
Published in Renal Failure, 2022
Yuchao Zhao, Meishun Cai, Zhenbin Jiang, Bao Dong, Yu Yan, Yina Wang, Li Zuo
There are three major complement pathways include the classical pathway, mannose-binding lectin (MBL) pathway, and alternative pathway. C4d is generated in both the classical and mannose-binding lectin complement pathways. C1q is the major precursor of classical complement activation. The presence of both C4d and C1q indicates the activation of the classical pathway, but identification of C4d without C1q is more consistent with MBL pathyway; C4d and C1q are both absent in alternative complement activation [5]. The complement activation pathway in iMN remains inconclusive. IgG4, which does not activate the classical complement pathway, is the predominant immunoglobulin in iMN, whereas IgG1 and IgG3 are present in a minority of patients [6]. Deposition of C4d is detectable in essentially 100% of patients with iMN [7]; however, C1q deposits are very weak or lacking in most patients with iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen in the pathogenesis of iMN [8]. Some evidence suggests that IgG4 anti-PLA2R antibodies can bind MBL to activate the lectin complement pathway [9]. Based on this evidence, we hypothesized that MBL-initiated complement activation is involved in the pathogenesis of iMN. Our objective was to identify the role of MBL in the pathogenesis of iMN and aMN, and to identify the association between MBL, anti-PLA2R antibodies, and clinical outcomes in patients with MN.
Neuroinflammation and psychiatric disorders: Relevance of C1q, translocator protein (18 kDa) (TSPO), and neurosteroids
Published in The World Journal of Biological Psychiatry, 2022
Rainer Rupprecht, Christian Rupprecht, Barbara Di Benedetto, Gerhard Rammes
In human post-mortem brain tissue of patients suffering from Alzheimer’s disease increased C1q expression was positively correlated with amyloid plaques (Tooyama et al. 2001). In addition, recent research reported increased serum C1q levels in depressed patients (Yang et al. 2020; Yao and Li 2020). These findings are intriguing because it is well known that cognitive disturbances occur during depression and depression may even constitute a risk factor for the development of Alzheimer’s disease (Saiz-Vazquez et al. 2021). Indeed, during inflammatory processes, astrocytes may indirectly regulate neuronal C1q expression through the release of secreted factors such as TGFß (Bialas and Stevens 2013). Because dysfunctional astrocytes characterise post-mortem brains of MDD patients, they might somehow contribute to the aberrant levels of serum C1q found in depressed patients. Moreover, altered C1q immune complexes have recently been identified as putative drug targets in schizophrenia (Maes et al. 2021). In addition, a proteomic study has delineated altered C1q expression in children suffering from autism (Corbett et al. 2007). As such, C1q may be considered as a marker of subtle inflammatory processes, which may be involved in a broad spectrum of psychiatric disorders. Moreover, in a mouse model of tauopathy it has recently been shown that atrophy and neuronal loss are reflected by TSPO PET labelling and C1q expression and that treatment with a TSPO ligand may reduce C1q levels in microglia (Fairley et al. 2021), which provides an interesting link between the complement system and TSPO.