Current and Future Approaches for Monitoring Responses to Anti-complement Therapeutics

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Dec 3

PMID 31787968

Citations 13

Authors

Maedeh Mohebnasab

Oskar Eriksson

Barbro Persson

Kerstin Sandholm

Camilla Mohlin

Markus Huber-Lang

Brendan J Keating

Kristina N Ekdahl

Bo Nilsson

Affiliations

Soon will be listed here.

Abstract

Aberrations in complement system functions have been identified as either direct or indirect pathophysiological mechanisms in many diseases and pathological conditions, such as infections, autoimmune diseases, inflammation, malignancies, and allogeneic transplantation. Currently available techniques to study complement include quantification of (a) individual complement components, (b) complement activation products, and (c) molecular mechanisms/function. An emerging area of major interest in translational studies aims to study and monitor patients on complement regulatory drugs for efficacy as well as adverse events. This area is progressing rapidly with several anti-complement therapeutics under development, in clinical trials, or already in clinical use. In this review, we summarized the appropriate indications, techniques, and interpretations of basic complement analyses, exemplified by a number of clinical disorders.

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References

Stanilova S, Slavov E . Comparative study of circulating immune complexes quantity detection by three assays--CIF-ELISA, C1q-ELISA and anti-C3 ELISA. J Immunol Methods. 2001; 253(1-2):13-21. DOI: 10.1016/s0022-1759(01)00370-2. View

Sandholm K, Persson B, Skattum L, Eggertsen G, Nyman D, Gunnarsson I . Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use. Front Immunol. 2019; 10:7. PMC: 6357986. DOI: 10.3389/fimmu.2019.00007. View

Yang S, McGookey M, Wang Y, Cataland S, Wu H . Effect of blood sampling, processing, and storage on the measurement of complement activation biomarkers. Am J Clin Pathol. 2015; 143(4):558-65. DOI: 10.1309/AJCPXPD7ZQXNTIAL. View

Heidenreich U, Mayer G, Herold M, Klotz W, Stempfl Al-Jazrawi K, Lhotta K . Sensitivity and specificity of autoantibody tests in the differential diagnosis of lupus nephritis. Lupus. 2009; 18(14):1276-80. DOI: 10.1177/0961203309345753. View

Wang H, Ricklin D, Lambris J . Complement-activation fragment C4a mediates effector functions by binding as untethered agonist to protease-activated receptors 1 and 4. Proc Natl Acad Sci U S A. 2017; 114(41):10948-10953. PMC: 5642699. DOI: 10.1073/pnas.1707364114. View

Risitano A, Marotta S, Ricci P, Marano L, Frieri C, Cacace F . Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT. Front Immunol. 2019; 10:1157. PMC: 6587878. DOI: 10.3389/fimmu.2019.01157. View

Tedesco F, Pausa M, Nardon E, Introna M, Mantovani A, Dobrina A . The cytolytically inactive terminal complement complex activates endothelial cells to express adhesion molecules and tissue factor procoagulant activity. J Exp Med. 1997; 185(9):1619-27. PMC: 2196305. DOI: 10.1084/jem.185.9.1619. View

Yuan X, Gu X, Crabb J, Yue X, Shadrach K, Hollyfield J . Quantitative proteomics: comparison of the macular Bruch membrane/choroid complex from age-related macular degeneration and normal eyes. Mol Cell Proteomics. 2010; 9(6):1031-46. PMC: 2877969. DOI: 10.1074/mcp.M900523-MCP200. View

Ekdahl K, Persson B, Mohlin C, Sandholm K, Skattum L, Nilsson B . Interpretation of Serological Complement Biomarkers in Disease. Front Immunol. 2018; 9:2237. PMC: 6207586. DOI: 10.3389/fimmu.2018.02237. View

10.

Ricklin D, Mastellos D, Reis E, Lambris J . The renaissance of complement therapeutics. Nat Rev Nephrol. 2017; 14(1):26-47. PMC: 5805379. DOI: 10.1038/nrneph.2017.156. View

11.

Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L . Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS One. 2016; 11(10):e0164646. PMC: 5074546. DOI: 10.1371/journal.pone.0164646. View

12.

Mayer M . On the destruction of erythrocytes and other cells by antibody and complement. Cancer Res. 1961; 21:1262-9. View

13.

Harris C, Heurich M, Rodriguez de Cordoba S, Morgan B . The complotype: dictating risk for inflammation and infection. Trends Immunol. 2012; 33(10):513-21. PMC: 3460238. DOI: 10.1016/j.it.2012.06.001. View

14.

Platts-Mills T, Ishizaka K . Activation of the alternate pathway of human complements by rabbit cells. J Immunol. 1974; 113(1):348-58. View

15.

Crabb J, Miyagi M, Gu X, Shadrach K, West K, Sakaguchi H . Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A. 2002; 99(23):14682-7. PMC: 137479. DOI: 10.1073/pnas.222551899. View

16.

Nilsson U, Nilsson B . Simplified assays of hemolytic activity of the classical and alternative complement pathways. J Immunol Methods. 1984; 72(1):49-59. DOI: 10.1016/0022-1759(84)90432-0. View

17.

Rego S, Dagan-Rosenfeld O, Zhou W, Sailani M, Limcaoco P, Colbert E . High-frequency actionable pathogenic exome variants in an average-risk cohort. Cold Spring Harb Mol Case Stud. 2018; 4(6). PMC: 6318774. DOI: 10.1101/mcs.a003178. View

18.

Nilsson B, Svensson K, Inganas M, Nilsson U . A simplified assay for the detection of C3a in human plasma employing a monoclonal antibody raised against denatured C3. J Immunol Methods. 1988; 107(2):281-7. DOI: 10.1016/0022-1759(88)90229-3. View

19.

Liszewski M, Java A, Schramm E, Atkinson J . Complement Dysregulation and Disease: Insights from Contemporary Genetics. Annu Rev Pathol. 2016; 12:25-52. PMC: 6020056. DOI: 10.1146/annurev-pathol-012615-044145. View

20.

Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Brodsky A . Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014; 370(7):632-9. DOI: 10.1056/NEJMoa1311084. View