A Multianalyte Assay Panel With Cell‐Bound Complement Activation Products Predicts Transition of Probable Lupus to American College of Rheumatology–Classified Lupus

ObjectivesTo evaluate the association between lupus severity and cell-bound complement activation products (CB-CAPs) or low complement proteins C3 and C4.MethodsAll subjects (n=495) fulfilled the American College of Rheumatology (ACR) classification criteria for SLE. Abnormal CB-CAPs (erythrocyte-bound C4d or B-lymphocyte-bound C4d levels >99th percentile of healthy) and complement proteins C3 and C4 were determined using flow cytometry and turbidimetry, respectively. Lupus severity was estimated using the Lupus Severity Index (LSI). Statistical analysis consisted of multivariable linear regression and groups comparisons.ResultsAbnormal CB-CAPs were more prevalent than low complement values irrespective of LSI levels (62% vs 38%, respectively, p<0.0001). LSI was low (median 5.44, IQR: 4.77–6.93) in patients with no complement abnormality, intermediate in patients with abnormal CB-CAPs (median 6.09, IQR: 5.31–8.20) and high in the group presenting with both abnormal CB-CAPs and low C3 and/or C4 (median 7.85, IQR: 5.51–8.37). Odds of immunosuppressant use was higher in subjects with LSI ≥5.95 compared with subjects with LSI <5.95 (1.60 vs 0.53, p<0.0001 for both). Multivariable regression analysis revealed that higher LSI scores associated with abnormal CB-CAPs—but not low C3/C4—after adjusting for younger age, race and longer disease duration (p=0.0001), which were also independent predictors of disease severity (global R2=0.145).ConclusionAbnormalities in complement activation as measured by CB-CAPs are associated with increased LSI.

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The Avise Lupus Test and Cell-bound Complement Activation Products Aid the Diagnosis of Systemic Lupus Erythematosus

The Open Rheumatology Journal ◽

10.2174/1874312901610010071 ◽

2016 ◽

Vol 10 (1) ◽

pp. 71-80 ◽

Cited By ~ 6

Author(s):

James Mossell ◽

John A. Goldman ◽

Derren Barken ◽

Roberta Vezza Alexander

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Complement Activation ◽

Clinical Utility ◽

Standard Of Care ◽

Classification Criteria ◽

Systemic Lupus ◽

American College Of Rheumatology ◽

Activation Products ◽

Test Result

Background: Systemic lupus erythematosus (SLE) is a multifaceted disease, and its diagnosis may be challenging. A blood test for the diagnosis of SLE, the Avise Lupus test, has been recently commercialized and validated in clinical studies. Objectives: To evaluate the use of the Avise Lupus test by community rheumatologists. Methods: The study is a longitudinal, case-control, retrospective review of medical charts. Cases had a positive test result, and controls had a negative result; all patients were anti-nuclear antibodies (ANA) positive but negative for SLE-specific autoantibodies. Features of SLE, diagnosis, and medications at two time points were recorded. Results: Twenty of the 23 cases (87%) and 4 of the 23 controls (17%) were diagnosed with SLE (sensitivity=83%; specificity=86%). More cases than controls (43% vs. 17%) fulfilled 4 American College of Rheumatology (ACR) classification criteria of SLE. Sensitivity of the test was significantly higher than the ACR score (83% vs. 42%, p=0.006). A higher percentage of patients who met the classification criteria had elevated cell-bound complement activation products (CB-CAPs) compared to patients who did not. Anti-rheumatic medications were used in a higher percentage of cases than controls (83% vs. 35% at baseline, p=0.002), suggesting that cases were treated more aggressively early on. Conclusion: A positive Avise Lupus test result aids in formulating a SLE diagnosis when diagnosis based on standard-of-care tests and clinical features may be challenging, and impacts patient management. Prospective studies will be performed to better evaluate the clinical utility of the test and of CB-CAPs as biomarkers of SLE.

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Role and regulation of early complement activation products in Alzheimer’s disease

Neuroinflammatory Mechanisms in Alzheimer’s Disease Basic and Clinical Research ◽

10.1007/978-3-0348-8350-4_3 ◽

2001 ◽

pp. 67-87

Author(s):

Robert Veerhuis ◽

Freek L. Van Muiswinkel ◽

C. Erik Hack ◽

Piet Eikelenboom

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Complement Activation ◽

Activation Products

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Radioimmunoassay for anaphylatoxins: A sensitive method for determining complement activation products in biological fluids

Analytical Biochemistry ◽

10.1016/0003-2697(84)90308-7 ◽

1984 ◽

Vol 136 (1) ◽

pp. 75-88 ◽

Cited By ~ 105

Author(s):

Janet L. Wagner ◽

Tony E. Hugli

Keyword(s):

Complement Activation ◽

Biological Fluids ◽

Activation Products ◽

Sensitive Method

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

Clinical Immunology and Immunopathology ◽

10.1006/clin.1995.1040 ◽

1995 ◽

Vol 74 (3) ◽

pp. 283-288 ◽

Cited By ~ 41

Author(s):

J.M. Porcel ◽

J. Ordi ◽

A. Castro-Salomo ◽

M. Vilardell ◽

M.J. Rodrigo ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Complement Activation ◽

Systemic Lupus ◽

Activation Products

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Complement Activation and Complement-Dependent Inflammation by Neisseria meningitidis Are Independent of Lipopolysaccharide

Infection and Immunity ◽

10.1128/iai.72.6.3344-3349.2004 ◽

2004 ◽

Vol 72 (6) ◽

pp. 3344-3349 ◽

Cited By ~ 38

Author(s):

Tom Sprong ◽

Anne-Sophie W. Møller ◽

Anna Bjerre ◽

Elisabeth Wedege ◽

Peter Kierulf ◽

...

Keyword(s):

Neisseria Meningitidis ◽

Complement Activation ◽

Oxidative Burst ◽

Whole Blood ◽

Meningococcal Sepsis ◽

Necrosis Factor Alpha ◽

Chemokine Production ◽

Inflammatory Protein ◽

Activation Products ◽

Factor Alpha

ABSTRACT Fulminant meningococcal sepsis has been termed the prototypical lipopolysaccharide (LPS)-mediated gram-negative septic shock. Systemic inflammation by activated complement and cytokines is important in the pathogenesis of this disease. We investigated the involvement of meningococcal LPS in complement activation, complement-dependent inflammatory effects, and cytokine or chemokine production. Whole blood anticoagulated with lepirudin was stimulated with wild-type Neisseria meningitidis H44/76 (LPS+), LPS-deficient N. meningitidis H44/76lpxA (LPS−), or purified meningococcal LPS (NmLPS) at concentrations that were relevant to meningococcal sepsis. Complement activation products, chemokines, and cytokines were measured by enzyme-linked immunosorbent assays, and granulocyte CR3 (CD11b/CD18) upregulation and oxidative burst were measured by flow cytometry. The LPS+ and LPS− N. meningitidis strains both activated complement effectively and to comparable extents. Purified NmLPS, used at a concentration matched to the amount present in whole bacteria, did not induce any complement activation. Both CR3 upregulation and oxidative burst were also induced, independent of LPS. Interleukin-1β (IL-1β), tumor necrosis factor alpha, and macrophage inflammatory protein 1α production was predominantly dependent on LPS, in contrast to IL-8 production, which was also markedly induced by the LPS− meningococci. In this whole blood model of meningococcal sepsis, complement activation and the immediate complement-dependent inflammatory effects of CR3 upregulation and oxidative burst occurred independent of LPS.

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Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus

Arthritis & Rheumatology ◽

10.1002/art.41093 ◽

2019 ◽

Vol 72 (1) ◽

pp. 78-88 ◽

Cited By ~ 9

Author(s):

Rosalind Ramsey‐Goldman ◽

Roberta Vezza Alexander ◽

Elena M. Massarotti ◽

Daniel J. Wallace ◽

Sonali Narain ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Complement Activation ◽

Systemic Lupus ◽

American College Of Rheumatology

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Complement activation products in acute heart failure: Potential role in pathophysiology, responses to treatment and impacts on long-term survival

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872617694674 ◽

2017 ◽

Vol 7 (4) ◽

pp. 348-357 ◽

Cited By ~ 4

Author(s):

Marten Trendelenburg ◽

Fabio Stallone ◽

Kateryna Pershyna ◽

Timo Eisenhut ◽

Raphael Twerenbold ◽

...

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Complement Activation ◽

Subgroup Analysis ◽

Potential Role ◽

Control Group ◽

Term Survival ◽

Activation Products

Background: Previous studies have indicated a correlation between heart failure, inflammation and poorer outcome. However, the pathogenesis and role of inflammation in acute heart failure (AHF) is incompletely studied and understood. The aim of our study was to explore the potential role of innate immunity – quantified by complement activation products (CAPs) – in pathophysiology, responses to treatment and impacts on long-term survival in AHF. Methods: In a prospective study enrolling 179 unselected patients with AHF, plasma concentrations of C4d, C3a and sC5b-9 were measured in a blinded fashion on the first day of hospitalisation and prior to discharge. The final diagnosis, including the AHF phenotype, was adjudicated by two independent cardiologists. Long-term follow-up was obtained. Findings in AHF were compared to that obtained in 75 healthy blood donors (control group). Results: Overall, concentrations of all three CAPs were significantly higher in patients with AHF than in healthy controls (all p < 0.001). In an age-adjusted subgroup analysis, significant differences could be confirmed for concentrations of C4d and sC5b-9, and these parameters further increased after 6 days of in-hospital treatment ( p < 0.001). In contrast, C3a levels in AHF patients did not differ from those of the control group in the age-adjusted subgroup analysis and remained constant during hospitalisation. Concentrations of C4d, C3a and sC5b-9 were significantly higher when AHF was triggered by an infection as compared to other triggers ( p < 0.001). In addition, CAP levels significantly correlated with each other ( r = 0.64–0.76), but did not predict death within 2 years. Conclusions: Activation of complement with increased plasma levels of C4d and sC5b-9 at admission and increasing levels during AHF treatment seems to be associated with AHF, particularly when AHF was triggered by an infection. However, CAPs do not have a prognostic value in AHF.

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