Systemic lupus erythematosus and C1q: A quantitative ELISA for determining C1q levels in serum

Dillon, Skyler P.; D’Souza, Anil; Kurien, Biji T.; Scofield, R. Hal

doi:10.1002/biot.200800273

Cited by 26 publications

(19 citation statements)

References 16 publications

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“…In preliminary experiments (Fig. S1D–E), the optimal C1q concentration (150 µg/ml) and incubation time (1 h) to obtain the highest percentage of C1q binding to AL while maintaining C1q concentration at near physiological levels was determined (C1q serum concentration is about 113 ± 40 µg/ml, ranging from 56 to 276 µg/ml depending on the studies and methods (40,41)). We found that C1q binds to human EAL and LAL with the same efficiency since about 55 to 60% of both EAL and LAL were C1q positive and have comparable MFI (Fig.…”

Section: Resultsmentioning

confidence: 99%

Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells

Benoit

Clarke

Morgado

et al. 2012

The Journal of Immunology

213

194

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Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like auto-immune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. Here, we developed an autologous system using primary human lymphocytes and monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I interferons (IFNs), IL-27 and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with AL conditioned media. Co-incubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose dependent manner and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1 dependent cleavage of IL-1β suggesting potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation providing potential therapeutic targets to control macrophage polarization, and thus inflammation and autoimmunity.

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Section: Resultsmentioning

confidence: 99%

Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells

Benoit

Clarke

Morgado

et al. 2012

The Journal of Immunology

213

194

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“…We therefore assessed whether inclusion of complement protein C1q protein would be able to block the adiponectin effect on phagocytosis. Neutrophils were pre-incubated with human serum C1q (at the physiological concentration of 100 μg/ml [38]) in order to allow binding to its receptors prior to the addition of adiponectin. However, the addition of C1q did not prevent adiponectin-mediated inhibition of neutrophil phagocytosis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Adiponectin Inhibits Neutrophil Phagocytosis of Escherichia coli by Inhibition of PKB and ERK 1/2 MAPK Signalling and Mac-1 Activation

Rossi

Lord

2013

PLoS ONE

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Full length adiponectin is a potent immune modulatory adipokine, impacting upon the actions of several immune cells. Neutrophil oxidative burst has been shown to decrease in response to adiponectin, and we speculated that it could have other effects on neutrophil function. Here we report that adiponectin reduces the phagocytic ability of human neutrophils, decreasing significantly the ingestion of opsonised E. coli by these cells in whole blood (p<0.05) and as isolated neutrophils (p<0.05). We then determined the mechanisms involved. We observed that the activation of Mac-1, the receptor engaged in complement-mediated phagocytosis, was decreased by adiponectin in response to E. coli stimulation. Moreover, treatment of neutrophils with adiponectin prior to incubation with E. coli significantly inhibited signalling through the PI3K/PKB and ERK 1/2 pathways, with a parallel reduction of F-actin content. Studies with pharmacological inhibitors showed that inhibition of PI3K/PKB, but not ERK 1/2 signalling was able to prevent the activation of Mac-1. In conclusion, we propose that adiponectin negatively affects neutrophil phagocytosis, reducing the uptake of E. coli and inhibiting Mac-1 activation, the latter by blockade of the PI3K/PKB signal pathway.

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“…We determined serum C1q levels as previously reported using a sandwich enzyme‐linked immunosorbant assay (ELISA) …”

Section: Methodsmentioning

confidence: 99%

Prolidase deficiency breaks tolerance to lupus-associated antigens

et al. 2013

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Background Prolidase deficiency is a rare autosomal recessive disease in which one of the last steps of collagen metabolism, cleavage of proline-containing dipeptides, is impaired. Only about 93 patients have been reported with about 10% also having systemic lupus erythematosus (SLE). Methods We studied a large extended Amish pedigree with four prolidase deficiency patients and three heterozygous individuals for lupus-associated autoimmunity. Eight unaffected Amish children served as normal controls. Prolidase genetics and enzyme activity were confirmed. Antinuclear antibodies (ANA) were determined using indirect immunofluorescence and antibodies against extractable nuclear antigens were determined by various methods, including double immunodiffusion, immunoprecipitation and multiplex bead assay. Serum C1q levels were determined by enzyme-linked immunosorbent assay. Results Two of the four homozygous prolidase deficiency subjects had a positive ANA. One had anti-double-stranded DNA, while another had precipitating anti-Ro. By the simultaneous microbead assay, three of the four had anti-Sm and anti-chromatin. One of the three heterozygous subjects had a positive ANA and immunoprecipitation of a 75 000 molecular weight protein. The unaffected controls had normal prolidase activity and were negative for autoantibodies. Conclusions Prolidase deficiency may be associated with the loss of immune tolerance to lupus-associated autoantigens even without clinical SLE.

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Systemic lupus erythematosus and C1q: A quantitative ELISA for determining C1q levels in serum

Cited by 26 publications

References 16 publications

Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells

Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells

Adiponectin Inhibits Neutrophil Phagocytosis of Escherichia coli by Inhibition of PKB and ERK 1/2 MAPK Signalling and Mac-1 Activation

Prolidase deficiency breaks tolerance to lupus-associated antigens

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