The Value of Complement Activation Products in the Assessment of Systemic Lupus Erythematosus Flares

Porcel, José M.; Ordi, J; Castro, Antoni; Vilardell, M; Rodrigo, María-José; T, Gené; Warburton, Fiona; Kraus, M; Vergani, Diego

doi:10.1006/clin.1995.1040

Cited by 54 publications

(35 citation statements)

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“…RAGE is a pattern recognition receptor that not only binds to several S100 proteins, HMGB1, AGE, MAC-1, and amyloid-b peptide (16)(17)(18)28), but also as we show in this paper, RAGE binds to HSP70, matricellular injury-related glycoprotein SPARC, complement component C3a, and CpG DNA oligos. These alarmin molecules are known to mediate various inflammatory diseases.…”

Section: Discussionsupporting

confidence: 51%

“…This process initiates a pathogenic cycle in which both the adaptive and the innate immune system collaborate to advance the disease. In addition to the hallmark anti-nuclear and other autoantibodies, serum levels of high-mobility group box protein (HMGB)1 (16), C3a (17), , and dsDNA (19) are consistently high in patients with lupus and correlate with the disease severity.…”

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confidence: 99%

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Complement C3a, CpG Oligos, and DNA/C3a Complex Stimulate IFN-α Production in a Receptor for Advanced Glycation End Product-Dependent Manner

Ruan

Winkler

et al. 2010

The Journal of Immunology

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The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor implicated in a number of diseases including autoimmune diseases. To further understand the pathogenic mechanism of RAGE in these diseases, we searched for additional ligands. We discovered that C3a bound to RAGE with an EC50 of 1.9 nM in an ELISA, and the binding was increased both in magnitude (by >2-fold) and in affinity (EC50 70 pM) in the presence of human stimulatory unmethylated cytosine-guanine-rich DNA A (hCpGAs). Surface plasmon resonance and fluorescence anisotropy analyses demonstrated that hCpGAs could bind directly to RAGE and C3a and form a ternary complex. In human PBMCs, C3a increased IFN-α production in response to low levels of hCpGAs, and this synergy was blocked by soluble RAGE or by an Ab directed against RAGE. IFN-α production was reduced in response to mouse CpGAs and C3a in RAGE−/− mouse bone marrow cells compared wild-type mice. Taken together, these data demonstrate that RAGE is a receptor for C3a and CpGA. Through direct interaction, C3a and CpGA synergize to increase IFN-α production in a RAGE-dependent manner and stimulate an innate immune response. These findings indicate a potential role of RAGE in autoimmune diseases that show accumulation of immunostimulatory DNA and C3a.

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

Complement C3a, CpG Oligos, and DNA/C3a Complex Stimulate IFN-α Production in a Receptor for Advanced Glycation End Product-Dependent Manner

Ruan

Winkler

et al. 2010

The Journal of Immunology

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“…in healthy subjects and 526AE 63 ngamL in acutely ill patients with active systemic lupus erythematosus (SLE). Similarly, Porcel et al 13 reported a maximum concentration of 267 ngaml in healthy subjects and 590 ngamL in patients with acute lupus. In patients undergoing haemodialysis, Chenoweth et al 14 noted a range of 115±867 ngaml in patients dialysed against a cuprophane membrane.…”

Section: Discussionmentioning

confidence: 83%

The influence of oral lipid loads on acylation stimulating protein (ASP) in healthy volunteers

Charlesworth

Peake

et al. 1998

Int J Obes

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OBJECTIVES: To examine the hypothesis that a sustained rise in plasma acylation stimulating protein (ASP, C3a desarg) accompanies the elevation in triacylglycerol that follows the ingestion of an oral fat load. DESIGN: Following an overnight fast, blood samples were obtained from healthy volunteers while fasting and 15 min, 1, 2, 4, 6 and 8 h following ingestion of: (i) a liquid meal, rich in dairy fat (eight subjects) and (ii) a semi-liquid meal, with higher total fat content and rich in polyunsaturated fat (six subjects). SUBJECTS AND METHODS: Four male and four female volunteers (age range: 22 ± 51 y; body mass index (BMI): 17.9 ± 26.9 kgam 2 ) received the ®rst meal. Six subjects (age range: 32 ± 60 y; BMI: 18.0 ± 28.4 kgam 2 ), including three from the ®rst study, received the second meal using the same protocol. ASP and C5a were measured by radioimmunoassay (RIA) and the complement proteins C3, factor B and C5 by radial immunodiffusion or nephelometry. Tumour necrosis factor (TNF)-a was measured by enhanced ELISA, and plasma cholesterol and triacylglycerol by an automated enzymatic method. The presence of chylomicrons was assessed in post-prandial plasma samples taken after the second meal. RESULTS: There was no signi®cant change in mean ASP concentration in either group at any time point, following ingestion of either meal. However, there was a signi®cant positive linear trend in ASP following the second fat challenge (ANOVA; P`0.05). There was also no change in complement proteins, plasma cholesterol or TNF-a. Plasma triacylglycerol rose signi®cantly after the ®rst and second meals (P`0.05 and P`0.001 at 2 h post-prandially); the mean maximum rise above the fasting level was 58 AE 41% and 89 AE 38% respectively (mean AE s.d.). Chylomicrons were detected in samples taken from each subject after the second meal. Analysis of individual ASP data showed a sustained rise in one subject after the ®rst meal and two subjects after the second meal. Substantial variation in ASP concentration was observed in samples taken in the ®rst 2 h post-prandially. CONCLUSION: There was no signi®cant change in ASP nor other complement proteins for either group of subjects following ingestion of the lipid loads. Individual data showed substantial variation in post-prandial ASP, but multiple plasma sampling did not de®ne the basis for this variation.

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“…Consumption of complements is represented by decreased levels of C3 and C4, lowered total hemolytic activity or the presence of complement activation products [67]. However, because low complement levels are less than ideal for assessing disease activity, many studies have investigated the potential of a number of complement activation products, such as C3a, C5a, C3d and C4d, as disease activity markers [68][69][70]. One study showed that assessment of serum complement activation products (C4d, Bb, C5b-9) was better than conventional C3 and C4 in distinguishing patients with varying degrees of lupus disease activity [69].…”

Section: Complement Activation Productsmentioning

confidence: 99%

“…They concluded that C4d and Bb were sensitive biomarkers of moderate-to-severe lupus disease activity and might be most helpful in situations where conventional C3 and C4 levels remained normal despite evidence of clinical disease activity. In addition, the terminal complex C5b-9 was reported to have a strong correlation with lupus disease activity [68]. However, complement activation occurs in other comorbidities such as infection, and complement activation products have low specificity, providing only a rough estimate of disease activity in SLE [70].…”

Section: Complement Activation Productsmentioning

confidence: 99%

Biomarkers for systemic lupus erythematosus: an update

Kim

Jung²,

Suh³

2015

International Journal of Clinical Rheumatology

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The Value of Complement Activation Products in the Assessment of Systemic Lupus Erythematosus Flares

Cited by 54 publications

References 0 publications

Complement C3a, CpG Oligos, and DNA/C3a Complex Stimulate IFN-α Production in a Receptor for Advanced Glycation End Product-Dependent Manner

Complement C3a, CpG Oligos, and DNA/C3a Complex Stimulate IFN-α Production in a Receptor for Advanced Glycation End Product-Dependent Manner

The influence of oral lipid loads on acylation stimulating protein (ASP) in healthy volunteers

Biomarkers for systemic lupus erythematosus: an update

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