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Complement system – disorders and diagnostics


Authors: J. Martínek 1,2,3;  A. Lochmanová 1,2;  J. Gumulec 4
Authors‘ workplace: Oddělení imunologie a alergologie, Zdravotní ústav se sídlem v Ostravě 1;  Ústav laboratorní medicíny, LF OU, Ostrava 2;  Ústav epidemiologie a ochrany veřejného zdraví, LF OU, Ostrava 3;  Klinika hematoonkologie, LF OU a FN Ostrava 4
Published in: Transfuze Hematol. dnes,29, 2023, No. Supplementum 3, p. 27-33.
Category:
doi: https://doi.org/10.48095/cctahd20233S27

Overview

The complement system is a key component of innate immunity. It consists of 50 plasma and membrane proteins that form three distinct but overlapping pathways of activation, as well as a common terminal lytic cascade and a network of regulators and receptors. Complement disorders may contribute to immunodeficiencies, autoimmunity, malignancies, infectious diseases, and diseases associated with complement dysregulation. Strict adherence to the rules of the preanalytical phase of the examination is essential for laboratory diagnosis. To comprehensively assess the function and involvement of complement in immunopathological processes, we need to perform a whole range of investigations (from functional tests, examination of individual complement components, to genetic analysis).

Keywords:

complement system – complement deficiency – laboratory diagnosis and interpretation


Sources

1. Frazer-Abel A, Kirschfink M, Prohászka Z. Expanding horizons in complement analysis and quality control. Front Immunol. 2021; 12: 1–12.

2. Sarma JV, Ward PA. The complement system. Cell Tissue Res. 2011; 343 (1): 227–235.

3. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010; 11 (9): 785–797.

4. Walport MJ: Complement. First of two parts. N Engl J Med. 2001; 344 (14): 1058–1066.

5. Walport MJ: Complement. Second of two parts. N Engl J Med. 2001; 344 (15): 140–144.

6. Kirschfink M, Mollnes TE. Modern complement analysis. Clin Diagn Lab Immunol. 2003; 10 (6): 982–989.

7. Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Köhl J. The role of the anaphylatoxins in health and disease. Mol Immunol. 2009; 46: 2753–2766.

8. Willrich MAV, Braun KMP, Moyer AM, Jeffrey DH, Frazer-Abel A. Complement testing in the clinical laboratory. Crit Rev Clin Lab Sci. 2021; 58 (7): 447–478.

9. Thurman, JM, Frazer-Abel A, Holers VM. The evolving landscape for complement therapeutics in rheumatic and autoimmune diseases. Arthritis Rheumatol (Hoboken, N.J.). 2017; 69 (11): 2102–2113.

10. Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2008; 23: 1957–1972.

11. Roumenina LT, Loirat C, Dragon-Durey MA, Halbwachs-Mecarelli L, Sautes-Fridman C, Fremeaux-Bacchi V. Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods. 2011; 365: 8–26.

12. Ding P, Xu Y, Li L, et al. Intracellular complement C5a/C5aR1 stabilizes b-catenin to promote colorectal tumorigenesis. Cell Rep. 2022; 39 (9): 110851.

13. Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest. 2017; 127 (3): 780–789.

14. Roumenina LT, Daugan MV, Petitprez F, et al. Context-dependent roles of complement in cancer. Nat Rev Cancer. 2019; 19: 698–715.

15. Hamilton RG, Giclas PC: Complement. In: Detrick B, Hamilton RG, Folds JD. Manual of molecular and clinical laboratory immunology, 7th ed. Washington. ASM Press. 2006; 113–140.

16. Martinek J, Lochman I. Komplementový systém a jeho laboratorní diagnostika. Alergie. 2013; 1: 55–61.

17. Mayer MM. Complement and complement fixation. In: Kabat E, Mayer MM, Experimental immunochemistry. Thomas CC, Springfield. 1961; 133–240.

18. Nilsson B, Ekdahl KN. Complement diagnostics: concepts, indications, and practical guidelines. Clin Dev Immunol. 2012; 2012: 962 702.

19. Hamilton RG, Giclas PC. Complement. In: Detrick B, Schmitz JL, Hamilton RG. Manual of molecular and clinical laboratory immunology, 8th ed. Washington. ASM Press. 2016; 107–132.

20. Dragon-Durey MA, Loirat C, Cloarec S, et al. Anti-Factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2005; 16: 555–563.

21. Józsi M, Strobel S, Dahse HM, et al. Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome. Blood. 2007; 110: 1516–1518.

22. Lee BH, Kwak SH, Shin JI, et al. Atypical hemolytic uremic syndrome associated with complement factor H autoantibodies and CFHR1/CFHR3 deficiency. Pediatr Res. 2009; 66: 336–340.

23. Watson R, Lindner S, Bordereau P, et al. Standardisation of the factor H autoantibody assay. Immunobiology. 2014; 219: 9–16.

24. Cataland SR, Holers VM, Geyer S, Yang S, Wu HM. Biomarkers of terminal complement activation confirm the diagnosis of aHUS and differentiate aHUS from TTP. Blood. 2014; 123 (24): 3733–3738.

25. Gavriilaki E, Yuan X, Ye Z, et al. Modified Ham test for atypical hemolytic uremic syndrome. Blood. 2015; 125 (23): 3637–3646.

26. Kolev M, Kemper C: Detection of cell membrane-bound CD46 using flow cytometry. Methods Mol Biol. 2014; 1100: 329–339.

27. Noris M, Bresin E, Mele C, et al. Genetic atypical hemolytic-uremic syndrome. In: Adam MP, Mirzaa GM, Pagon RA, et al. Seattle. GeneReviews. 2021.

28. Yoshida Y, Miyata T, Matsumoto M, et al. A novel quantitative hemolytic assay coupled with restriction fragment length polymorphisms analysis enabled early diagnosis of atypical hemolytic uremic syndrome and identified unique predisposing mutations in Japan. PLoS One. 2015; 10: e0124655.

29. Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013; 8: 554–562.

30. Noris M, Remuzzi G: Atypical hemolytic-uremic syndrome. N Engl J Med. 2009; 361: 1676–1687.

31. Caprioli J, Noris M, Brioschi S, et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006; 108 (4): 1267–1279.

32. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013; 368 (23): 2169–2181.

33. Cugno M, Gualtierotti R, Possenti I, et al. Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome. J Thromb Haemost. 2014; 12: 1440–1448.

34. Noris M, Galbusera M, Gastoldi S, et al. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood. 2014; 124: 1715–1726.

35. Gilbert RD, Fowler DJ, Angus E, Hardy SA, Stanley L, Goodship TH. Eculizumab therapy for atypical haemolytic uraemic syndrome due to a gain-of-function mutation of complement factor B. Pediatr Nephrol. 2013; 28: 1315–1318.

36. Ardissino G, Tel F, Sgarbanti M, et al. Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome: an update. Pediatr Nephrol. 2018; 33 (3): 457–461.

37. Goodship TH, Cook HT, Fakhouri F, et al. Atypical hemolytic uremic syndrome and C3glomerulopathy: conclusions from a BKidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2017; 91: 539–551.

38. Cataland SR, Holers VM, Geyer S, Yang S, Wu HM. Biomarkers of terminal complement activation confirm the diagnosis of aHUS and differentiate aHUS from TTP. Blood. 2014; 123 (24): 3733–3738.

39. Cataland S, Ariceta G, Chen P, et al. Discordance between free C5 and CH50 complement assays in measuring complement C5 inhibition in patients with aHUS treated with ravulizumab. Blood. 2019; 134 (1): 1099.

40. Willrich MAV, Ladwig PM, Martinez MA, et al. Monitoring ravulizumab effect on complement assays. J Immunol Methods. 2021; 490: 112944.

41. Sobotková M. Poruchy v komplementovém systému. Vnitř Lék. 2020; 66 (6): 346–352.

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