The ability of released proteins (Yops) and surface lipopolysaccharides (LPS) from the wild-type strain Yersinia enterocolitica 8081-L2, serotype 0:8 to influence the complement activity was determined. Yops and LPS from wild-type and mutant strains showed different ability to affect the classical pathway (CP) functional complement activity in vitro. The serum CP activity was inhibited during the infection induced with six Y. enterocolitica and three Y. pseudotuberculosis strains in rabbits. The changed complement activity might be of importance for the course of Yersinia infections.
- MeSH
- Yersinia pseudotuberculosis Infections immunology MeSH
- Yersinia Infections immunology MeSH
- Complement Inactivating Agents immunology MeSH
- Complement Pathway, Classical immunology MeSH
- Rabbits MeSH
- Lipopolysaccharides immunology MeSH
- Disease Models, Animal MeSH
- Bacterial Outer Membrane Proteins immunology MeSH
- Complement Hemolytic Activity Assay MeSH
- Yersinia enterocolitica immunology MeSH
- Yersinia pseudotuberculosis immunology MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Complement Inactivating Agents MeSH
- Lipopolysaccharides MeSH
- Bacterial Outer Membrane Proteins MeSH
- Keywords
- ANTIBODIES *, COMPLEMENT *, ESCHERICHIA COLI *, LIVER *, PHAGOCYTOSIS *,
- MeSH
- Escherichia coli * MeSH
- Phagocytosis * MeSH
- Immunoglobulins * MeSH
- Liver * MeSH
- Complement System Proteins * MeSH
- Humans MeSH
- Antibodies * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Immunoglobulins * MeSH
- Complement System Proteins * MeSH
- Antibodies * MeSH
The role of complement has been demonstrated in experimental models of neuromyelitis optica (NMO), however, only few studies have analysed complement components longitudinally in NMO patients. We measured serum or plasma concentrations of anti-C1q antibodies and complement split products C3a and C4a and soluble C5b-9 in patients with NMO, multiple sclerosis and healthy controls. NMO patients had higher levels of C3a and anti-C1q antibodies than healthy controls. C3a levels correlated with disease activity, neurological disability and aquaporin-4 IgG in NMO patients suggesting a role of the alternative pathway of complement in the pathogenesis of NMO and supporting the strategy of therapeutic complement inhibition.
- Keywords
- Aquaporin-4 IgG, C1q antibodies, Complement, Neuromyelitis optica,
- MeSH
- Complement Activation immunology MeSH
- Aquaporin 4 immunology MeSH
- Autoantibodies blood immunology MeSH
- Adult MeSH
- Immunoglobulin G blood immunology MeSH
- Complement C1q immunology metabolism MeSH
- Complement C3a immunology metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Neuromyelitis Optica immunology MeSH
- Prospective Studies MeSH
- Multiple Sclerosis, Relapsing-Remitting immunology MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aquaporin 4 MeSH
- AQP4 protein, human MeSH Browser
- Autoantibodies MeSH
- Immunoglobulin G MeSH
- Complement C1q MeSH
- Complement C3a MeSH
Complement activation was studied in six patients treated with immunoadsorption columns Ig-ADSOPAK for myasthenia gravis. Mean therapy duration was 18.6 months (range 4-28 months). Prior and after each procedure, concentrations of C3 and C4 were examined, hemolytic activity of complement by a classic pathway (CH50) was determined, as well as terminal complement complex (TCC). After each immunoadsorption procedure, a decrease of C3 and C4 was noted (median 21.19% and 19.68%, respectively). The CH50 and TCC follow-up showed statistically significant complement activation. Median of TCC accrual was 60.21% and median of CH50 decrease was 23.24%. No clinical manifestations of complement activation were present. With increasing number of procedures a marked decrease of TCC activation was observed in five patients, which was statistically significant in three of them (p < 0.05). This finding may indicate an immunomodulating effect of long-term adsorption therapy. With increasing number of procedures, an inhibition in complement system reactivity occurs. This result, however, has to be confirmed on a larger group of patients.
- MeSH
- Complement Activation * MeSH
- Adult MeSH
- Immunosorbent Techniques MeSH
- Complement C4 analysis MeSH
- Complement C3 analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Myasthenia Gravis blood therapy MeSH
- Aged MeSH
- Blood Component Removal * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Complement C4 MeSH
- Complement C3 MeSH
The complement system is an important component of innate immunity, which is part of the first line of defense against infections. In addition, complement plays an important role in the removal of apoptotic and damaged endogenous cells and, according to recent discoveries, contributes significantly to the homeostasis of the organism. The complement system includes several dozen soluble and membrane-bound proteins, which, after activation, function as a cascade, at the end of which is the elimination of the infectious agent. Complement activation occurs through one of 3 pathways (classical, lectin, and alternative) and all 3 pathways lead to the central C3 component. The cleavage of C3 starts the activation of the so-called effector terminal cascade, which participates in the elimination of pathogens through pro-inflammatory mechanisms, opsonization and, at the end, the creation of a channel in the basement membrane. The systematic control of complement activation plays an important role, because that represents prevention against damage to one's own tissues. Especially, the alternative pathway, which provides more than 80% of the activity of the terminal complement cascade, requires tight control. Dysregulation of complement and especially its alternative pathways is behind many acute and chronic diseases.
- Keywords
- C3 nephropathy, Complement, aHUS, alternative pathway, haemolytic uremic syndrome, thrombotic microangiopathy,
- MeSH
- Complement Activation * immunology MeSH
- Complement System Proteins * immunology physiology MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Complement System Proteins * MeSH
The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM
- MeSH
- Adult MeSH
- Immunologic Factors metabolism MeSH
- Complement C1q immunology metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Lupus Nephritis blood complications immunology MeSH
- Predictive Value of Tests MeSH
- Antibodies blood MeSH
- Aged MeSH
- Antibody Specificity immunology MeSH
- Lupus Erythematosus, Systemic blood complications immunology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Immunologic Factors MeSH
- Complement C1q MeSH
- Antibodies MeSH
No changes in immunoglobulin (IgG, IgM and IgA) and complement components C3 and C4 levels could be observed in patients suffering from both recurrent and acute nasal polyposis. However, in both groups of patients a significant decrease of the alternative pathway of complement activation (up to 80%) was found. In addition, patients suffering from the acute disease showed even decreased classical complement pathway (up to 20%). Examination of complement activation pathways was shown to be advantageous for the follow-up of the course of this disease.
- MeSH
- Acute Disease MeSH
- Complement Pathway, Alternative * MeSH
- Adult MeSH
- Immunoglobulins biosynthesis MeSH
- Complement C4 analysis MeSH
- Complement C3 analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Nasal Polyps blood immunology MeSH
- Recurrence MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Immunoglobulins MeSH
- Complement C4 MeSH
- Complement C3 MeSH
The complement cascade comprises soluble and cell surface proteins and is an important arm of the innate immune system. Once activated, the complement system rapidly generates large quantities of protein fragments that are potent mediators of inflammatory, vasoactive and metabolic responses. Although complement is crucial to host defence and homeostasis, its inappropriate or uncontrolled activation can also drive tissue injury. For example, the complement system has been known for more than 50 years to be activated by glomerular immune complexes and to contribute to autoimmune kidney disease. Notably, the latest research shows that complement is also activated in kidney diseases that are not traditionally thought of as immune-mediated, including haemolytic-uraemic syndrome, diabetic kidney disease and focal segmental glomerulosclerosis. Several complement-targeted drugs have been approved for the treatment of kidney disease, and additional anti-complement agents are being investigated in clinical trials. These drugs are categorically different from other immunosuppressive agents and target pathological processes that are not effectively inhibited by other classes of immunosuppressants. The development of these new drugs might therefore have considerable benefits in the treatment of kidney disease.
- MeSH
- Complement Activation MeSH
- Autoimmune Diseases * MeSH
- Kidney Glomerulus pathology MeSH
- Complement System Proteins metabolism MeSH
- Kidney metabolism MeSH
- Humans MeSH
- Kidney Diseases * metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Complement System Proteins MeSH
Efficacy of immunosuppressive treatment of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by its toxicity. With the replacement of cyclophosphamide with rituximab, serious adverse events seem to be associated especially with high-dose corticosteroids. Activation of alternative complement pathway plays an important role in the pathogenesis of AAV. Avacopan (C5a receptor inhibitor) was demonstrated to have at least similar efficacy and better safety (in terms of corticosteroid-related adverse events) compared with high-dose corticosteroids in the induction treatment of AAV. Other modes of the inhibition of alternative complement pathway are currently tested in AAV or could be considered on the basis of the experience in other glomerular diseases.
- Keywords
- ANCA, ANCA - associated vasculitis, C5a, avacopan, complement,
- MeSH
- Complement Pathway, Alternative MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * MeSH
- Cyclophosphamide adverse effects MeSH
- Humans MeSH
- Antibodies, Antineutrophil Cytoplasmic MeSH
- Rituximab therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Cyclophosphamide MeSH
- Antibodies, Antineutrophil Cytoplasmic MeSH
- Rituximab MeSH
- Keywords
- AGGLUTINATION *, ANTIBODIES *, CATTLE *, CELL STRUCTURE *, COMPLEMENT *, ELECTROPHORESIS *, ENDOTOXINS *, ESCHERICHIA COLI *, EXPERIMENTAL LAB STUDY *, GUINEA PIGS *, HEMAGGLUTINATION *, HEMOLYSIS *, PHAGOCYTOSIS *, RABBITS *, SALMONELLA *, SALMONELLA TYPHOSA *, SHIGELLA *, SWINE *,
- MeSH
- Agglutination * MeSH
- Electrophoresis * MeSH
- Endotoxins * MeSH
- Escherichia coli * MeSH
- Phagocytosis * MeSH
- Cell Physiological Phenomena * MeSH
- Hemagglutination * MeSH
- Hemagglutination Tests * MeSH
- Hemolysis * MeSH
- Complement System Proteins * MeSH
- Rabbits MeSH
- Guinea Pigs MeSH
- Swine MeSH
- Antibodies * MeSH
- Salmonella typhi * MeSH
- Salmonella * MeSH
- Shigella * MeSH
- Cattle MeSH
- Research * MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Guinea Pigs MeSH
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Endotoxins * MeSH
- Complement System Proteins * MeSH
- Antibodies * MeSH
