Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies against C1q (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE). The anti-C1q antibodies strongly correlate with the occurrence of lupus nephritis and low-circulating C1q levels. Previous studies have demonstrated that myeloid cells, i.e., dendritic cells and macrophages, are a major source of C1q. However, a direct effect of anti-C1q on C1q secretion by macrophages has not yet been established. In the present study, we investigated the C1q secretion profile of in vitro human monocyte-derived macrophages (HMDMs) obtained from healthy donors and from patients with SLE. The effect of SLE patient-derived anti-C1q bound to immobilized C1q (imC1q) and imC1q alone on HMDMs was investigated by C1q secretion levels, the expression of membrane-bound and intracellular C1q using flow cytometry and ImageStreamX technology, and testing the ability of secreted C1q to activate the classical pathway (CP) of the complement. Bound anti-C1q induced significantly greater C1q secretion levels as compared with imC1q alone or healthy donor IgG. The extent of C1q secretion by HMDMs correlated with IgG anti-C1q levels of patients with SLE but not of healthy controls. Furthermore, bound autoantibodies and imC1q induced continuous and de novo C1q synthesis as evident by the intracellular C1q content, which correlated with C1q secretion levels. Finally, secreted C1q was able to activate the CP, as reflected by C4b deposition. Interestingly, anti-C1q-dependent C1q secretion could also be observed in SLE patient-derived cells. In conclusion, our data indicate that imC1q-bound anti-C1q strongly stimulate the C1q production by HMDMs. Anti-C1q-induced C1q secretion might be an important immune-modulatory factor in SLE.
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PMID:Anti-C1q autoantibodies from patients with systemic lupus erythematosus induce C1q production by macrophages. 2763 Feb 15

Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal. Importantly, the process is tightly controlled by the binding of complement inhibitors C4b-binding protein and factor H, which attenuates late steps of complement activation and inflammation. Furthermore, factor H becomes actively internalized by apoptotic cells, where it catalyzes the cleavage of intracellular C3 to C3b. The intracellularly derived C3b additionally opsonizes the cell surface further supporting safe and fast clearance and thereby aids to prevent autoimmunity. Internalized factor H also binds nucleosomes and directs monocytes into production of anti-inflammatory cytokines upon phagocytosis of such complexes. Disturbances in the complement-mediated clearance of dying cells result in persistence of autoantigens and development of autoimmune diseases like systemic lupus erythematosus, and may also be involved in development of age-related macula degeneration.
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PMID:Complement in removal of the dead - balancing inflammation. 2778 29

CR1 (CD35, Complement Receptor type 1 for C3b/C4b) is a high molecular weight membrane glycoprotein of about 200 kDa that controls complement activation, transports immune complexes, and participates in humoral and cellular immune responses. CR1 is present on the surface of many cell types, including erythrocytes, and exhibits polymorphisms in length, structure (Knops, or KN, blood group), and density. The average density of CR1 per erythrocyte (CR1/E) is 500 molecules per erythrocyte. This density varies from one individual to another (100-1,200 CR1/E) and from one erythrocyte to another in the same individual. We present here a robust flow cytometry method to measure the density of CR1/E, including in subjects expressing a low density, with the help of an amplifying immunostaining system. This method has enabled us to show the lowering of CR1 erythrocyte expression in diseases such as Alzheimer's disease (AD), systemic lupus erythematosus (SLE), AIDS, or malaria.
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PMID:Measuring Erythrocyte Complement Receptor 1 Using Flow Cytometry. 3251 May 17


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