Usefulness and analytical performances of complement multiplex assay for measuring complement biomarkers in plasma

Meuleman, Marie-Sophie; Duval, Anna; Grunenwald, Anne; Rezola Artero, Mikel; Dermani, Mohamed; Peliconi, Julie; Revel, Margot; Vieira-Martins, Paula; Courbebaisse, Marie; Parfait, Béatrice; Lebeaux, David; Friedlander, Gérard; Roumenina, Lubka; Chauvet, Sophie; Frémeaux-Bacchi, Véronique; Dragon-Durey, Marie-Agnès

doi:10.1016/j.cca.2023.117750

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Here, we combined different complement screening approaches to get closer to what we define as Humoral Complementomics – simultaneous exploration of a large number of complement proteins, activation fragments, and autoantibodies against complement proteins in patient plasma. For this purpose, we employed a novel validated multiplexed ELISA 19 for quantification of complement proteins and activation fragments, combined with the quantification of C4d neoepitope, well-validated in the literature and associated with poor prognosis in different cancers and in lupus nephritis, 7 , 28 , 29 an ELISA for MASP2 and the recently described tests for quantification of the C1s/C1INH and the MASP1/C1INH complexes. 20 , 30 Furthermore, we developed an in-house method for simultaneous screening of plasma IgG, IgM, and IgA autoantibodies against complement proteins.…”

Section: Discussionmentioning

confidence: 99%

“…We have selected the MicroVue Complement multiplex (QuidelOrtho) assay based on a good correlation of the measured values with the gold standard monoplex methods (nephelometry for C3 and C4; ELISA for FH, FI, sC5b-9), the capacity to distinguish patients with genetic deficiency of complement components and their accordance with the expected normal range in the literature. 19 Two panels were used: Panel 1: Ba, Bb, C3a, C5a, sC5b-9, C4a, Factor H, Factor I (8 plex kit HQ1M210421 16,400 01) and Panel 2: C1q, C2 Intact, C3 Intact, C4 Intact, C5 Intact, FD, FP (7 plex kit HQ2M210316 16,400 03). Samples were diluted 1/100 th for Panel 1 and 1/1000 th for panel 2 and processed as recommended by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

“… 20 C4a measurements were excluded from this study due to the significant variability in the dynamic range observed across healthy control measurements which has been previously reported. 19 Calprotectin levels were measured by ELISA (CalproLab ELISA (ALP) – RUO – Svar Life Science). CRP was measured by immunoturbidimetry (Beckman-Coulter).…”

Section: Methodsmentioning

confidence: 99%

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Humoral complementomics – exploration of noninvasive complement biomarkers as predictors of renal cancer progression

Revel,

Rezola Artero,

Hamidi

et al. 2024

OncoImmunology

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Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose a Humoral Complementomics approach: a work-up of assays to comprehensively evaluate complement proteins, activation fragments, and autoantibodies targeting complement proteins in plasma, which we correlated with the intratumoral complement activation, and/or local production, focusing on localized and metastatic clear cell renal cell carcinoma (ccRCC). In two prospective ccRCC cohorts, plasma C2, C5, Factor D and properdin were elevated compared to healthy controls, reflecting an inflammatory phenotype that correlated with plasma calprotectin levels but did not associate with CRP or with patient prognosis. Conversely, autoantibodies against the complement C3 and the reduced form of FH (a tumor neo-epitope reported in lung cancer) correlated with a favorable outcome. Our findings pointed to a specific group of patients with elevated plasma C4d and C1s-C1INH complexes, indicating the initiation of the classical pathway, along with elevated Ba and Bb, indicating alternative pathway activation. Boostrapped Lasso regularized Cox regression revealed that the most predictive complement biomarkers were elevated plasma C4d and Bb levels at the time of surgery, which correlated with poor prognosis. In conclusion, we propose Humoral Complementomics as an unbiased approach to study the global state of the complement system in any pathological plasma sample and disease context. Its implementation for ccRCC revealed that elevated C4d and Bb in plasma are promising prognostic biomarkers, correlating with shorter progression-free survival.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Humoral complementomics – exploration of noninvasive complement biomarkers as predictors of renal cancer progression

Revel,

Rezola Artero,

Hamidi

et al. 2024

OncoImmunology

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“…Since C activation can occur in several scenarios, the specificity of a single C-component test is low, so a panel of tests should be preferred ( 90 ). C multiplex ELISA assays, such as panels for simultaneous testing of C activation fragments and intact components or regulators ( 91 ), may be particularly advantageous from a technical and reproducibility standpoint. Thus, multiplex assays can help to address the need for a thorough analysis of the status of C activation and regulation and ensure a comprehensive overview of the C cascade.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities

Balduit,

Agostinis,

Mangogna

et al. 2024

Front. Immunol.

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The complement system (C) is a crucial component of the innate immune system. An increasing body of research has progressively shed light on the pivotal role of C in immunological tolerance at the feto-maternal interface. Excessive C activation or impaired C regulation may determine the onset of pregnancy-related pathological conditions, including pre-eclampsia (PE). Thus, several studies have investigated the presence of C components or split products in blood matrixes (i.e., plasma, serum), urine, and amniotic fluid in PE. In the current study, we systematically reviewed the currently available scientific literature reporting measurements of C components as circulating biomarkers in PE, based on a literature search using Pubmed, Scopus, and Embase databases. A total of 41 out of 456 studies were selected after full-text analysis. Fourteen studies (34.1%) were identified as measuring the blood concentrations of the classical pathway, 5 (12.1%) for the lectin pathway, 28 (68.3%) for the alternative pathway, 17 (41.5%) for the terminal pathway components, and 16 (39%) for C regulators. Retrieved results consistently reported C4, C3, and factor H reduction, and increased circulating levels of C4d, Bb, factor D, C3a, C5a, and C5b-9 in PE compared to normal pregnancies, depicting an overall scenario of excessive C activation and aberrant C regulation. With evidence of C activation and dysregulation, C-targeted therapy is an intriguing perspective in PE management. Moreover, we also discussed emerging pitfalls in C analysis, mainly due to a lack of experimental uniformity and biased cohort selection among different studies and laboratories, aiming to raise a more comprehensive awareness for future standardization.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024503070.

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“…Complement regulating factors such as FB, FH, FI, FD, and other products derived from the various complement pathways can be assessed utilizing monoclonal antibodies that recognize and target specific epitopes [34]. More recently, the simultaneous quantification of complement proteins (C1q, C2, C3, C4, C5, FD, FP, FH, FI) and cleavage fragments (C4a, C3a, C5a, Bb, Ba, sC5b9) using multiplex ELISA assays has also been reported [35].…”

Section: Quantitative Assessment Of Complement Systemmentioning

confidence: 99%

Complements and Their Role in Systemic Disorders

Wang,

Tang,

Loe

et al. 2024

Cureus

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The complement system is critical to the body's innate defense against exogenous pathogens and clearance of endogenous waste, comprising the classical, alternative, and lectin pathways. Although tightly regulated, various congenital and acquired diseases can perturb the complement system, resulting in specific complement deficiencies. Systemic rheumatic, neurological, ophthalmological, renal, and hematological disorders are some prototypical complement-mediated diseases. An adequate understanding of the mechanisms of the normal complement system and the pathophysiology of complement dysregulation is critical for providing diagnostic clues and appropriately managing these conditions. This review guides clinicians in understanding the role of complement factors in systemic diseases and what diagnostic and therapeutic options are available for complement-mediated disorders.

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Usefulness and analytical performances of complement multiplex assay for measuring complement biomarkers in plasma

Cited by 8 publications

References 43 publications

Humoral complementomics – exploration of noninvasive complement biomarkers as predictors of renal cancer progression

Humoral complementomics – exploration of noninvasive complement biomarkers as predictors of renal cancer progression

Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities

Complements and Their Role in Systemic Disorders

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