The complement system in systemic autoimmune disease
Section snippets
Three activating pathways of complement
Complement is part of the innate immune system and is one of the main effector mechanisms of antibody-mediated immunity. The complement system comprises more than 30 plasma and membrane-bound proteins [1], [2].
Activation of the complement system involves participation of a large number of plasma proteins including C1q, C1r, C1s, C2 through C9, factor B, factor D, and properdin. There are three pathways of complement activation, i.e. the classical, alternative and lectin pathway. All three
The complement system and systemic small vessel vasculitis
Vasculitis is an inflammatory process of blood vessels, histopathologically characterized by inflammation and fibrinoid necrosis of the vessel wall. An attempt to classify the diverse forms of vasculitis resulted in the Chapel Hill international consensus definitions, which used the vessel size and the histopathology of the lesions as the main determinants of classification [21].
The complement system and anti-glomerular basement membrane disease
Anti-glomerular basement membrane (anti-GBM) disease is a rare but life-threatening disease caused by IgG autoantibodies against the glomerular basement membrane. Typical manifestations of anti-GBM disease are rapidly progressive glomerulonephritis accompanied by pulmonary hemorrhage. Anti-GBM disease is one of the few human autoimmune diseases in which the pathogenic autoantigen has been identified. It is designated as the Goodpasture antigen and comprises the noncollagenous domain (NC1) of
The complement system and systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by multi-organ involvement, including serosa, joints, central nervous system, skin and kidneys, in association with an array of autoantibodies, in particular antibodies to double stranded DNA.
The role of complement in the pathogenesis of SLE is paradoxical. On the one hand, complement components appear to mediate autoantibody-initiated tissue damage. On the other hand, the complement system appears to
The complement system and anti-phospholipid antibody syndrome
The anti-phospholipid antibody syndrome (APS) is a clinical condition characterized by arterial and venous thrombosis and pregnancy complications in association with anti-phospholipid (aPL) antibodies. In addition to recurrent miscarriage and fetal death, pregnancy complications in women with APS include preeclampsia, placental insufficiency, and fetal growth restriction. Using a murine model of APS induced by passive transfer of human anti-phospholipid antibodies, it has been shown that
The complement system and systemic sclerosis
Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of skin and internal organs, with skin thickening either restricted to distal extremities and face (limited disease), or affecting also proximal extremities and/or trunk (diffuse disease). Both endothelium, epithelium, fibroblasts, the innate and adaptive immune system are involved in its pathogenesis. Endothelial cell damage may be the initiating factor. The immunopathological events in SSc have not been
The complement system and primary Sjögren's syndrome
Primary Sjögren's syndrome is a systemic autoimmune disease that presents with sicca symptoms of mucosa surfaces, in particular the eyes (xerophthalmia) and mouth (xerostomia). The histological hallmark is a focal lymphocytic infiltration of the exocrine glands.
A large number of autoantibodies have been reported in primary Sjogren's syndrome. In some cases the antibodies correlate with the extent and severity of disease. In particular, antibodies to the ubiquitous autoantigens 52-kDa SSA/Ro,
The complement system and dermatomyositis
The inflammatory myopathies are a heterogeneous group of subacute, chronic, or acutely acquired diseases of skeletal muscle. They have in common the presence of moderate to severe muscle weakness and inflammation. On the basis of well-defined clinical, demographic, histological, and immunopathological criteria, the inflammatory myopathies form three major and discrete groups: polymyositis, dermatomyositis, and sporadic inclusion-body myositis [101].
Dermatomyositis is a complement-mediated
The complement system and rheumatoid arthritis
Rheumatoid arthritis (RA) is a systemic disease characterized by chronic inflammation of the synovium and subsequent destruction of cartilage and bone. There is abundant evidence that complement activation is involved in the pathogenesis of RA.
In RA, accelerated consumption and a responsive hyper-production of complement components have been reported in synovial fluids. Compatible with complement consumption, complement activity of joint fluid from patients with RA was shown to be significantly
Conclusion
The complement system participates in the pathogenesis of many systemic autoimmune diseases. Besides the classical pathway via immune complex formation, e.g. in. cryoglobulinemic vasculitis and systemic lupus erythematosus, also the alternative pathway is involved. Increasing evidence shows the role of complement activation via the alternative pathway in many classical immune-complex mediated diseases. Because of the major role of complement in mediating target organ damage, approaches to
Conflict of interest
None declared.
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2023, Developmental and Comparative ImmunologyCitation Excerpt :It is found that the domains involved in the complement system like C1q, fibrinogen-like (FBG), complement control protein (CCP), complement urchin-bone (CUB), carbohydrate-recognition domain (CRD), thrombospondin type 1 repeats (TSP1) and low-density lipoprotein a (LDLa) are greatly expanded in molluscs, indicating that the components of complement system are more complex and diverse in molluscs. C3 is the core component in the complement system, which is composed of three polypeptide chains (α, β, and γ) and can be activated to generate multiple active fragments (Chen et al., 2010; Gros et al., 2008; Zhu et al., 2005). Until now, C3 homologues have been identified in several molluscan species, such as Pacific oyster C. gigas (Wang et al., 2017), pearl oyster Pinctada fucata (Wang et al., 2021), Yesso scallop Patinopecten yessoensis (Liao et al., 2018), thick shell mussel Mytilus coruscus (Chen et al., 2018b), razor clam Sinonovacula constricta (Peng et al., 2016), pearl mussel Hyriopsis cumingii (Wang et al., 2019), carpet-shell clam Ruditapes decussatus (Prado-Alvarez et al., 2009), and Hawaiian bobtail squid Euprymna scolopes (Castillo et al., 2009).
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