Detection of autoantibodies against the globular domain of human C1q in the sera of systemic lupus erythematosus patients

Tsacheva, Ivanka; Radanova, Maria; Todorova, Nadezhda; Argirova, Trenka; Kishore, Uday

doi:10.1016/j.molimm.2006.09.009

Cited by 33 publications

(32 citation statements)

References 18 publications

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“…Although antiC1q cannot account for hypocomplementemia in all patients with SLE, there is a strong correlation between the occurrence of these autoantibodies and hypocomplementemia (13,23,50). An increasing number of studies suggest a pathogenic role of anti-C1q Abs in SLE, particularly in the development of proliferative lupus nephritis (24,51), because anti-C1q Abs strongly correlate with renal flares (52). In contrast to many other autoantibodies described in SLE, antiC1q Abs are directed against a highly functional molecule.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against C1q in Systemic Lupus Erythematosus Are Antigen-Driven

Schaller

Bigler

Danner

et al. 2009

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Autoantibodies against C1q in Systemic Lupus Erythematosus Are Antigen-Driven

Schaller

Bigler

Danner

et al. 2009

The Journal of Immunology

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“…C1q is known to play an important role in immune complex diseases, such as systemic lupus erythematosus, Arthus reaction, autoantibody-induced arthritis, glomerulonephritis, and experimental autoimmune encephalitis. 11,[64][65][66] In addition, mast cells have been associated with these diseases. 36,[67][68][69][70] Our findings provide a molecular mechanism linking C1q and activation of these inflammatory cells.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between the α2β1 integrin and c-met/HGF-R regulates innate immunity

McCall-Culbreath¹,

Li²,

Zutter

2008

Blood

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Data from several investigators suggest that the ␣2␤1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1, endorepellin, and several viruses, is required for innate immunity and regulation of autoimmune/ allergic disorders. We demonstrated that the innate immune response to Listeria monocytogenes required ␣2␤1 integrin expression by peritoneal mast cells (PMCs). Ligation of the ␣2␤1 integrin by C1q contained in immune complexes comprised of Listeria and antibody was required for PMC activation in vitro and in vivo. However, ligation of the ␣2␤1 integrin alone was insufficient to activate cytokine secretion, suggesting that one or more additional signals emanating from a coreceptor were required for PMC activation. Here, we demonstrate that C1q, but neither other complement proteins nor FcR␥, is required for early innate immune response to Listeria. IntroductionThe role of the ␣2␤1 integrin in the innate and acquired immune response has been an area of active investigation. We initially reported that the ␣2␤1 integrin-deficient mice exhibited markedly diminished inflammatory responses to Listeria monocytogenes because of a requirement for ␣2␤1 integrin expression on peritoneal mast cells (PMCs) for mast-cell activation and cytokine release in vivo. 1 Although the ␣2␤1 integrin serves as a receptor for several matrix and nonmatrix ligands, the ligand for the integrin during the PMC response to infection was unknown. 2,3 We demonstrated that C1q complement protein and collectin family members, including mannose binding lectin and surfactant protein A, all served as ligands for the integrin. 4 In addition, the ␣2␤1 integrin was required for mast-cell activation in vitro in response to Listeria. However, ligation of the ␣2␤1 integrin alone was insufficient to activate cytokine secretion because mast-cell adhesion to collagen or C1q alone failed to support cytokine secretion. 4 We hypothesized that one or more additional signals emanating from an additional receptor was required to activate mast-cell cytokine secretion in response to immune complexes. At that time, we presented 2 alternative models by which ␣2␤1 integrin-ligand interactions may stimulate mast-cell activation and cytokine secretion. Our first model proposed that ligation of the ␣2␤1 integrin simultaneously with a second, costimulatory receptor elicited mast-cell activation, in a manner reminiscent of the role proposed for the ␣2␤1 integrin and the glycoprotein VI/Fc receptor common ␥ chain (FcR␥) during platelet adhesion to collagen. 5,6 In our second model, binding of the ␣2␤1 integrin to an immune complex containing C1q may directly activate the complement cascade, resulting in the deposition of C3b or iC3b and generation of complement byproducts, such as C3a or C5a, which would subsequently stimulate mast cell activation. [7][8][9] We now report that neither the FcR␥ nor components of the complement cascade are required in ␣2␤1 integrin-dependent mast-cell activation. Instead, we describe a novel coreceptor...

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“…12,19 An assay for the detection of autoantibodies against the globular domain of human C1q was introduced for the first time in 2007. 20 Several commercial assays are currently available for the detection of anti-C1q antibodies 15 but none of them have been approved by the Food and Drug Administration because of lack of prospective studies and unknown inter-test variability. Nevertheless, some of the anti-C1q antibody assays have been used in clinical studies, [21][22][23][24][25][26][27] and a recent study showed good correlation between a commercial kit with a clinically validated in-house enzymelinked immunosorbent assay (ELISA).…”

Section: Detection Methodsmentioning

confidence: 99%

Anti-C1q in systemic lupus erythematosus

Stojan

Petri

2016

Lupus

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C1q is the first component of the classical complement pathway. Both clinically validated inhouse ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays. Lupus (2016) 25, 873-877.

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Detection of autoantibodies against the globular domain of human C1q in the sera of systemic lupus erythematosus patients

Cited by 33 publications

References 18 publications

Autoantibodies against C1q in Systemic Lupus Erythematosus Are Antigen-Driven

Autoantibodies against C1q in Systemic Lupus Erythematosus Are Antigen-Driven

Crosstalk between the α2β1 integrin and c-met/HGF-R regulates innate immunity

Anti-C1q in systemic lupus erythematosus

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