Genomes and Genes
Summary: A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
- Fang Q, Yu F, Tan Y, Xu L, Wu L, Liu G, et al. Anti-C1q antibodies and IgG subclass distribution in sera from Chinese patients with lupus nephritis. Nephrol Dial Transplant. 2009;24:172-8 pubmed publisher..Anti-C1q antibodies are prevalent in LN and are closely associated with diffuse proliferative lesions. IgG2 anti-C1q might be pathogenic and IgG3 anti-C1q might be a more specific biomarker for monitoring disease activity. ..
- Jesus A, Silva C, Carneiro Sampaio M, Sheinberg M, Mangueira C, Marie S, et al. Anti-C1q antibodies in juvenile-onset systemic lupus erythematosus. Ann N Y Acad Sci. 2009;1173:235-8 pubmed publisher..42, P = 0.0004, 95% CI 0.19-0.60). Our results confirm a low frequency of anti-C1q antibody in our lupus populations, but the presence of anti-Clq antibodies appears to be a good marker for JSLE diagnosis. ..
- Sjöberg A, Nyström S, Hammarstrom P, Blom A. Native, amyloid fibrils and beta-oligomers of the C-terminal domain of human prion protein display differential activation of complement and bind C1q, factor H and C4b-binding protein directly. Mol Immunol. 2008;45:3213-21 pubmed publisher..Taken together the present study indicates that complement activation may be an important factor in human prion diseases, suggesting that complement induced activities may prove relevant therapeutic targets. ..
- Hamad O, Nilsson P, Wouters D, Lambris J, Ekdahl K, Nilsson B. Complement component C3 binds to activated normal platelets without preceding proteolytic activation and promotes binding to complement receptor 1. J Immunol. 2010;184:2686-92 pubmed publisher..However, the generation of C3(H(2)O) represents nonproteolytic activation of C3 and after factor I cleavage may act as a ligand for receptor binding. ..
- Naresha S, Suryawanshi A, Agarwal M, Singh B, Joshi P. Mapping the complement C1q binding site in Haemonchus contortus calreticulin. Mol Biochem Parasitol. 2009;166:42-6 pubmed publisher..One way by which this protein acts is by inhibiting the classical complement pathway by binding to complement C1q protein. Understanding CalR-C1q interaction is important to develop methods to enhance host immune response...
- Flores Langarica A, Sebti Y, Mitchell D, Sim R, Macpherson G. Scrapie pathogenesis: the role of complement C1q in scrapie agent uptake by conventional dendritic cells. J Immunol. 2009;182:1305-13 pubmed..Our results show that C1q participates in PrP(Sc) uptake by cDCs, revealing a critical role for cDCs in initial prion capture, an event that takes place before the PrP(Sc) accumulation within the follicular DC network. ..
- Paidassi H, Tacnet Delorme P, Garlatti V, Darnault C, Ghebrehiwet B, Gaboriaud C, et al. C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition. J Immunol. 2008;180:2329-38 pubmed..Given its versatile recognition properties, these data suggest that C1q has the unique ability to sense different markers which collectively would provide strong eat me signals, thereby allowing efficient apoptotic cell removal. ..
- Qiu Y, Marquez Curtis L, Janowska Wieczorek A. Mesenchymal stromal cells derived from umbilical cord blood migrate in response to complement C1q. Cytotherapy. 2012;14:285-95 pubmed publisher..Our findings suggest new molecular mechanisms of MSC migration that may contribute to their clinical application in tissue repair. ..
- Severance E, Gressitt K, Halling M, Stallings C, Origoni A, Vaughan C, et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiol Dis. 2012;48:447-53 pubmed publisher..Here, we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia (n=38), non-recent onset schizophrenia (n=61) ..
- Paidassi H, Tacnet Delorme P, Verneret M, Gaboriaud C, Houen G, Duus K, et al. Investigations on the C1q-calreticulin-phosphatidylserine interactions yield new insights into apoptotic cell recognition. J Mol Biol. 2011;408:277-90 pubmed publisher..Together, these observations indicate that CRT, C1q, and PS are all closely involved in the uptake of apoptotic cells and strongly suggest a combinatorial role of these three molecules in the recognition step. ..
- Stoyanova V, Petrova S, Tchorbadjieva M, Deliyska B, Vasilev V, Tsacheva I. New insight into the autoimmunogenicity of the complement protein C1q. Mol Immunol. 2011;48:678-82 pubmed publisher..The presence of anti-gC1q in both healthy and diseased humans also implies that these antibodies, unlike anti-CLR, may have a contribution to an onset of autoimmunity. ..
- Csencsits K, Burrell B, Lu G, Eichwald E, Stahl G, Bishop D. The classical complement pathway in transplantation: unanticipated protective effects of C1q and role in inductive antibody therapy. Am J Transplant. 2008;8:1622-30 pubmed publisher..In contrast, the protective effects of anti-CD40L mAb were less compromised in C1q-/- recipients. Hence, this study reveals unanticipated roles for C1q in the rejection process. ..
- Potlukova E, Jiskra J, Limanova Z, Kralikova P, Smutek D, Mareckova H, et al. Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease. Clin Exp Immunol. 2008;153:96-101 pubmed publisherAutoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis...
- Benoit M, Tenner A. Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression. J Neurosci. 2011;31:3459-69 pubmed publisher..These results show that C1q can directly promote neuronal survival, thereby demonstrating new interactions between immune proteins and neuronal cells that may facilitate neuroprotection. ..
- Shimono C, Manabe R, Yamada T, Fukuda S, Kawai J, Furutani Y, et al. Identification and characterization of nCLP2, a novel C1q family protein expressed in the central nervous system. J Biochem. 2010;147:565-79 pubmed publisher..These results suggest that nCLP2 plays roles in synaptic function and maintenance in the CNS. ..
- Racila E, Link B, Weng W, Witzig T, Ansell S, Maurer M, et al. A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma. Clin Cancer Res. 2008;14:6697-703 pubmed publisher..The purpose of this study was to explore the relationship between the C1qA() polymorphism and the clinical response to rituximab in patients with follicular lymphoma...
- Yu Y, Huang H, Wang Y, Yu Y, Yuan S, Huang S, et al. A novel C1q family member of amphioxus was revealed to have a partial function of vertebrate C1q molecule. J Immunol. 2008;181:7024-32 pubmed..Our study on the primitive form of C1q family in protochordate will shed a light on understanding the gradual functional evolution of C1q family and eventual formation of mammalian homologues. ..
- Galvan M, Luchetti S, Burgos A, Nguyen H, Hooshmand M, Hamers F, et al. Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury. J Neurosci. 2008;28:13876-88 pubmed publisher..05). Together, these data suggest that initiation of the classical complement pathway via C1q is detrimental to recovery after SCI. ..
- Baruah P, Dumitriu I, Malik T, Cook H, Dyson J, Scott D, et al. C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells. Blood. 2009;113:3485-93 pubmed publisher..Our novel data suggest that C1q augments the production of IL-12p70 by mouse and human DCs after CD40 triggering and plays important roles in sustaining the maturation of DCs and guiding the activation of T cells. ..
- Hirata A, Kishida K, Kobayashi H, Nakatsuji H, Funahashi T, Shimomura I. Correlation between serum C1q-adiponectin/total adiponectin ratio and polyvascular lesions detected by vascular ultrasonography in Japanese type 2 diabetics. Metabolism. 2013;62:376-85 pubmed publisher..Serum C1q-APN/Total-APN ratio correlates with atherosclerosis detected by polyvascular vascular ultrasonography, independent of gender and visceral adiposity, in T2DM. ..
- Hong Q, Sze C, Lin S, Lee M, He R, Schultz L, et al. Complement C1q activates tumor suppressor WWOX to induce apoptosis in prostate cancer cells. PLoS ONE. 2009;4:e5755 pubmed publisher..Under complement C1q- or C6-free conditions, WOX1 and ERK were mainly present in the cytoplasm without phosphorylation, whereas ..
- Bigler C, Schaller M, Perahud I, Osthoff M, Trendelenburg M. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells. J Immunol. 2009;183:3512-21 pubmed publisherAutoantibodies against complement C1q (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE). They strongly correlate with the occurrence of severe lupus nephritis, suggesting a pathogenic role in SLE...
- Jalili A, Marquez Curtis L, Shirvaikar N, Wysoczynski M, Ratajczak M, Janowska Wieczorek A. Complement C1q enhances homing-related responses of hematopoietic stem/progenitor cells. Transfusion. 2010;50:2002-10 pubmed publisher..We demonstrated that C1q primes the responses of CD34+ HSPCs to an SDF-1 gradient, which may enhance their ability to stay within BM niches, suggesting that the C1q/C1qRp axis contributes to HSPC homing/retention in BM. ..
- Chen G, Tan C, Teh B, Lu J. Molecular mechanisms for synchronized transcription of three complement C1q subunit genes in dendritic cells and macrophages. J Biol Chem. 2011;286:34941-50 pubmed publisher..STAT1 instead regulated C1qB promoter through IRF8 induction. Collectively, our results reveal a novel transcriptional mechanism by which the expression of the three C1q genes is synchronized. ..
- Chu Y, Jin X, Parada I, Pesic A, Stevens B, Barres B, et al. Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc Natl Acad Sci U S A. 2010;107:7975-80 pubmed publisher..Results indicate that epileptogenesis in C1q KO mice is related to a genetically determined failure to prune excessive excitatory synapses during development. ..
- Gestal C, Pallavicini A, Venier P, Novoa B, Figueras A. MgC1q, a novel C1q-domain-containing protein involved in the immune response of Mytilus galloprovincialis. Dev Comp Immunol. 2010;34:926-34 pubmed publisher..The high sequence variability suggests that somatic diversification of these nonself recognition molecules could have occurred. ..
- Hosszu K, Santiago Schwarz F, Peerschke E, Ghebrehiwet B. Evidence that a C1q/C1qR system regulates monocyte-derived dendritic cell differentiation at the interface of innate and acquired immunity. Innate Immun. 2010;16:115-27 pubmed publisher..Thus, specific C1q/C1q receptor (R) interactions may control the transition from the monocyte state (innate immunity) toward the professional antigen-presenting cell state (adaptive immunity). ..
- Lattin J, Greenwood K, Daly N, Kelly G, Zidar D, Clark R, et al. Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival. Mol Immunol. 2009;47:340-7 pubmed publisher..Here we show that ARRB2 mRNA and protein expression is enriched in macrophages, and that it regulates complement C1q expression and cell survival...
- Rayner L, Kadkhodayi Kholghi N, Heenan R, Gor J, Dalby P, Perkins S. The solution structure of rabbit IgG accounts for its interactions with the Fc receptor and complement C1q and its conformational stability. J Mol Biol. 2013;425:506-23 pubmed publisher..The intact rabbit IgG structures explained the ability of its two ligands, the Fc receptor and complement C1q, to bind to the top of its Fc region that is fully accessible and unhindered by the Fab regions.
- Lood C, Gullstrand B, Truedsson L, Olin A, Alm G, Rönnblom L, et al. C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis Rheum. 2009;60:3081-90 pubmed publisher..Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients. ..
- Naito A, Sumida T, Nomura S, Liu M, Higo T, Nakagawa A, et al. Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes. Cell. 2012;149:1298-313 pubmed publisher..We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration...
- Galvan M, Greenlee Wacker M, Bohlson S. C1q and phagocytosis: the perfect complement to a good meal. J Leukoc Biol. 2012;92:489-97 pubmed publisher..In addition, we highlight our recent findings demonstrating that C1q elicits a macrophage phenotype that is tailored specifically for clearance of apoptotic cells. ..
- Elkon K, Santer D. Complement, interferon and lupus. Curr Opin Immunol. 2012;24:665-70 pubmed publisher..Together, these findings provide both direct and indirect links between two key pathways implicated in lupus pathogenesis: complement and IFN. ..
- Tahtouh M, Croq F, Vizioli J, Sautiere P, Van Camp C, Salzet M, et al. Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord. Mol Immunol. 2009;46:523-31 pubmed publisher..Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms...
- Nayak A, Ferluga J, Tsolaki A, Kishore U. The non-classical functions of the classical complement pathway recognition subcomponent C1q. Immunol Lett. 2010;131:139-50 pubmed publisher..The range of function that C1q has been shown to perform also provides clues for the undiscovered functions of a number of C1q family members. ..
- Fraser D, Pisalyaput K, Tenner A. C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. J Neurochem. 2010;112:733-43 pubmed publisher..The data are consistent with a protective role for C1q in the CNS during early stages of cell death by enhancing microglial clearance of apoptotic cells and suppressing proinflammatory cytokines. ..
- Katsumata Y, Miyake K, Kawaguchi Y, Okamoto Y, Kawamoto M, Gono T, et al. Anti-C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: a controlled study of 126 consecutive patients. Arthritis Rheum. 2011;63:2436-44 pubmed publisher..00097). These findings indicate that anti-C1q antibodies are associated with SLE global activity but not specifically with active lupus nephritis. ..
- Yuzaki M. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers. Eur J Neurosci. 2010;32:191-7 pubmed publisher..We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. ..
- Kozyro I, Korosteleva L, Chernoshej D, Danner D, Sukalo A, Trendelenburg M. Autoantibodies against complement C1q in acute post-streptococcal glomerulonephritis. Clin Immunol. 2008;128:409-14 pubmed publisherAutoantibodies against complement C1q (anti-C1q) strongly correlate with the occurrence of severe lupus nephritis...
- Kong P, Zhang H, Wang L, Zhou Z, Yang J, Zhang Y, et al. AiC1qDC-1, a novel gC1q-domain-containing protein from bay scallop Argopecten irradians with fungi agglutinating activity. Dev Comp Immunol. 2010;34:837-46 pubmed publisher..These results indicated that AiC1qDC-1 functioned as a pattern recognition receptor in the immune defense of scallops against pathogens and provided clues for illuminating the evolution of the complement classical pathway. ..
- Son M, Santiago Schwarz F, Al Abed Y, Diamond B. C1q limits dendritic cell differentiation and activation by engaging LAIR-1. Proc Natl Acad Sci U S A. 2012;109:E3160-7 pubmed publisher..The discovery of C1q interactions with LAIR-1 and LAIR-2 lends much needed insight into molecular mechanisms operating to prevent the loss of tolerance, particularly in systemic lupus erythematosus. ..
- Lu J, Teh B, Wang L, Wang Y, Tan Y, Lai M, et al. The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol. 2008;5:9-21 pubmed publisher..C1q deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of C1q, its expression, and classical and regulatory functions. ..
- Depboylu C, Schorlemmer K, Klietz M, Oertel W, Weihe E, Höglinger G, et al. Upregulation of microglial C1q expression has no effects on nigrostriatal dopaminergic injury in the MPTP mouse model of Parkinson disease. J Neuroimmunol. 2011;236:39-46 pubmed publisher..In conclusion, C1q is upregulated and considered to be a marker of microglial activation in the nigrostriatal system after subchronic MPTP, but nigrostriatal dopaminergic injury may be not affected by C1q in this model. ..
- Nakatsuji H, Kishida K, Kobayashi H, Funahashi T, Shimomura I. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes. Diabetes Res Clin Pract. 2013;99:e14-7 pubmed publisher..The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index. ..