References
Key articles
Brodszki N, Frazer-Abel A, Grumach AS, et al. European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) complement guideline: deficiencies, diagnosis, and management. J Clin Immunol. 2020 May;40(4):576-91.Full text Abstract
Grumach AS, Kirschfink M. Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach. Mol Immunol. 2014 Oct;61(2):110-7. Abstract
Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2021 revision and update. Allergy. 2022 Jul;77(7):1961-90.Full text Abstract
Reference articles
1. Mastellos DC, Hajishengallis G, Lambris JD. A guide to complement biology, pathology and therapeutic opportunity. Nat Rev Immunol. 2024 Feb;24(2):118-41. Abstract
2. Jayaraman A, Walachowski S, Bosmann M. The complement system: a key player in the host response to infections. Eur J Immunol. 2024 Nov;54(11):e2350814.Full text Abstract
3. Hajishengallis G, Reis ES, Mastellos DC, et al. Novel mechanisms and functions of complement. Nat Immunol. 2017 Nov 16;18(12):1288-8. Abstract
4. Reis ES, Mastellos DC, Hajishengallis G, et al. New insights into the immune functions of complement. Nat Rev Immunol. 2019 Aug;19(8):503-16.Full text Abstract
5. Ekdahl KN, Teramura Y, Hamad OA, et al. Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation. Immunol Rev. 2016 Nov;274(1):245-69. Abstract
6. Bekassy Z, Lopatko Fagerström I, Bader M, et al. Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation. Nat Rev Immunol. 2022 Jul;22(7):411-28.Full text Abstract
7. Zipfel PF, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol. 2009 Oct;9(10):729-40. Abstract
8. Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013 Apr 15;190(8):3831-8.Full text Abstract
9. Karasu E, Nilsson B, Köhl J, et al. Targeting complement pathways in polytrauma- and sepsis-induced multiple-organ dysfunction. Front Immunol. 2019;10:543.Full text Abstract
10. Koski CL, Sanders ME, Swoveland PT, et al. Activation of terminal components of complement in patients with Guillain-Barré syndrome and other demyelinating neuropathies. J Clin Invest. 1987 Nov;80(5):1492-7.Full text Abstract
11. Saez-Calveras N, Stuve O. The role of the complement system in multiple sclerosis: a review. Front Immunol. 2022 Aug 10;13:970486.Full text Abstract
12. Bohlson SS, Tenner AJ. Complement in the brain: contributions to neuroprotection, neuronal plasticity, and neuroinflammation. Annu Rev Immunol. 2023 Apr 26;41:431-52.Full text Abstract
13. Tenner AJ, Petrisko TJ. Knowing the enemy: strategic targeting of complement to treat Alzheimer disease. Nat Rev Neurol. 2025 May;21(5):250-64.Full text Abstract
14. Ekdahl KN, Huang S, Nilsson B, et al. Complement inhibition in biomaterial- and biosurface-induced thromboinflammation. Semin Immunol. 2016 Jun;28(3):268-77.Full text Abstract
15. Brodszki N, Frazer-Abel A, Grumach AS, et al. European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) complement guideline: deficiencies, diagnosis, and management. J Clin Immunol. 2020 May;40(4):576-91.Full text Abstract
16. Degn SE, Jensenius JC, Thiel S. Disease-causing mutations in genes of the complement system. Am J Hum Genet. 2011 Jun 10;88(6):689-705.Full text Abstract
17. Skattum L, Van deuren M, Van der poll T, et al. Complement deficiency states and associated infections. Mol Immunol. 2011 Aug;48(14):1643-55. Abstract
18. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev. 1991 Jul;4(3):359-95.Full text Abstract
19. Schröder-Braunstein J, Kirschfink M. Complement deficiencies and dysregulation: pathophysiological consequences, modern analysis, and clinical management. Mol Immunol. 2019 Oct;114:299-311. Abstract
20. West EE, Kemper C. Complosome - the intracellular complement system. Nat Rev Nephrol. 2023 Jul;19(7):426-39.Full text Abstract
21. King BC, Blom AM. Intracellular complement and immunometabolism: the advantages of compartmentalization. Eur J Immunol. 2024 Aug;54(8):e2350813.Full text Abstract
22. Mayilyan KR. Complement genetics, deficiencies, and disease associations. Protein Cell. 2012 Jul;3(7):487-96.Full text Abstract
23. Merle NS, Church SE, Fremeaux-Bacchi V, et al. Complement system part I - molecular mechanisms of activation and regulation. Front Immunol. 2015 Jun 2;6:262.Full text Abstract
24. Bohlson SS, Garred P, Kemper C, et al. Complement nomenclature-deconvoluted. Front Immunol. 2019;10:1308.Full text Abstract
25. Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol. 2013 Nov;33(6):479-92.Full text Abstract
26. Lhotta K, Janecke AR, Scheiring J, et al. A large family with a gain-of-function mutation of complement C3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure. Clin J Am Soc Nephrol. 2009 Aug;4(8):1356-62.Full text Abstract
27. Urban A, Volokhina E, Felberg A, et al. Gain-of-function mutation in complement C2 protein identified in a patient with aHUS. J Allergy Clin Immunol. 2020 Oct;146(4):916-9.e11.Full text Abstract
28. Fakhouri F, Frémeaux-Bacchi V. Thrombotic microangiopathy in aHUS and beyond: clinical clues from complement genetics. Nat Rev Nephrol. 2021 Aug;17(8):543-53. Abstract
29. Grumach AS, Kirschfink M. Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach. Mol Immunol. 2014 Oct;61(2):110-7. Abstract
30. Kindle G, Alligon M, Albert MH, et al. Inborn errors of immunity: manifestation, treatment, and outcome - an ESID registry 1994-2024 report on 30,628 patients. medRxiv. 2025 Apr 16:2025.02.20.25322586.Full text Abstract
31. Kim VHD, Upton JEM, Derfalvi B, et al. Inborn errors of immunity (primary immunodeficiencies). Allergy Asthma Clin Immunol. 2025 Jan 8;20(suppl 3):76.Full text Abstract
32. Unsworth DJ. Complement deficiency and disease. J Clin Pathol. 2008 Sep;61(9):1013-7. Abstract
33. Ellison RT 3rd, Kohler PF, Curd JG, et al. Prevalence of congenital or acquired complement deficiency in patients with sporadic meningococcal disease. N Engl J Med. 1983 Apr 21;308(16):913-6. Abstract
34. Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022 Oct;42(7):1473-507.Full text Abstract
35. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2021 revision and update. Allergy. 2022 Jul;77(7):1961-90.Full text Abstract
36. Levy JH, Freiberger DJ, Roback J. Hereditary angioedema: current and emerging treatment options. Anesth Analg. 2010 May 1;110(5):1271-80.Full text Abstract
37. Caccia S, Suffritti C, Cicardi M. Pathophysiology of hereditary angioedema. Pediatr Allergy Immunol Pulmonol. 2014 Dec 1;27(4):159-63.Full text Abstract
38. Grumach AS, Riedl MA, Cheng L, et al. Hereditary angioedema diagnosis: reflecting on the past, envisioning the future. World Allergy Organ J. 2025 Jun;18(6):101060.Full text Abstract
39. Bork K, Staubach-Renz P, Hardt J. Angioedema due to acquired C1-inhibitor deficiency: spectrum and treatment with C1-inhibitor concentrate. Orphanet J Rare Dis. 2019 Mar 13;14(1):65.Full text Abstract
40. Shi Y, Wang C. Where we are with acquired angioedema due to C1 inhibitor deficiency: a systematic literature review. Clin Immunol. 2021 Sep;230:108819. Abstract
41. Zuraw BL, Bork K, Bouillet L, et al. Hereditary angioedema with normal C1 inhibitor: an updated International Consensus Paper on diagnosis, pathophysiology, and treatment. Clin Rev Allergy Immunol. 2025 Mar 7;68(1):24.Full text Abstract
42. Wang RX, Newman SA. Urticarial vasculitis. Immunol Allergy Clin North Am. 2024 Aug;44(3):483-502. Abstract
43. Macedo AC, Isaac L. Systemic lupus erythematosus and deficiencies of early components of the complement classical pathway. Front Immunol. 2016 Feb 24;7:55.Full text Abstract
44. Coss SL, Zhou D, Chua GT, et al. The complement system and human autoimmune diseases. J Autoimmun. 2023 May;137:102979.Full text Abstract
45. Trendelenburg M. Autoantibodies against complement component C1q in systemic lupus erythematosus. Clin Transl Immunology. 2021 Apr 29;10(4):e1279.Full text Abstract
46. Carroll MC. A protective role for innate immunity in systemic lupus erythematosus. Nat Rev Immunol. 2004 Oct;4(10):825-31. Abstract
47. Buso H, Triaille C, Flinn AM, et al. Update on hereditary C1q deficiency: pathophysiology, clinical presentation, genotype and management. Curr Opin Allergy Clin Immunol. 2024 Dec 1;24(6):427-33. Abstract
48. Weinstein A, Alexander RV, Zack DJ. A review of complement activation in SLE. Curr Rheumatol Rep. 2021 Feb 10;23(3):16.Full text Abstract
49. Lewis LA, Ram S. Meningococcal disease and the complement system. Virulence. 2014 Jan 1;5(1):98-126.Full text Abstract
50. UK Health Security Agency. The complete routine immunisation schedule from February 2022. Feb 2022 [internet publication].Full text
51. Centers for Disease Control and Prevention. Child and adolescent immunization schedule by age: recommendations for ages 18 years or younger, United States, 2025. Oct 2025 [internet publication].Full text
52. Centers for Disease Control and Prevention. Adult immunization schedule by age: recommendations for ages 19 years or older, United States, 2025. Oct 2025 [internet publication].Full text
53. Noris M, Remuzzi G. Genetics of immune-mediated glomerular diseases: focus on complement. Semin Nephrol. 2017 Sep;37(5):447-63. Abstract
54. Willows J, Brown M, Sheerin NS. The role of complement in kidney disease. Clin Med (Lond). 2020 Mar;20(2):156-60.Full text Abstract
55. Petr V, Thurman JM. The role of complement in kidney disease. Nat Rev Nephrol. 2023 Dec;19(12):771-87. Abstract
56. Smith RJH, Appel GB, Blom AM, et al. C3 glomerulopathy - understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019 Mar;15(3):129-43.Full text Abstract
57. Wooden B, Nester CM, Bomback AS. Update on C3 glomerulopathy. Adv Kidney Dis Health. 2024 May;31(3):223-33. Abstract
59. Corvillo F, Okrój M, Nozal P, et al. Nephritic factors: an overview of classification, diagnostic tools and clinical associations. Front Immunol. 2019 Apr 24;10:886.Full text Abstract
60. Welsh SJ, Zhang Y, Smith RJH. Acquired drivers of C3 glomerulopathy. Clin Kidney J. 2025 Mar;18(3):sfaf022.Full text Abstract
61. Donadelli R, Sinha A, Bagga A, et al. HUS and TTP: traversing the disease and the age spectrum. Semin Nephrol. 2023 Jul;43(4):151436. Abstract
63. Wilke GA, Apte RS. Complement regulation in the eye: implications for age-related macular degeneration. J Clin Invest. 2024 May 1;134(9):e178296.Full text Abstract
64. Fritsche LG, Igl W, Bailey JN, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016 Feb;48(2):134-43.Full text Abstract
65. Hill A, DeZern AE, Kinoshita T, et al. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers. 2017 May 18;3:17028. Abstract
66. Risitano AM, Frieri C, Urciuoli E, et al. The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: from a pathogenic mechanism to a therapeutic target. Immunol Rev. 2023 Jan;313(1):262-78.Full text Abstract
67. Ozen A, Comrie WA, Ardy RC, et al. CD55 deficiency, early-onset protein-losing enteropathy, and thrombosis. N Engl J Med. 2017 Jul 6;377(1):52-61.Full text Abstract
68. Almutawea LM, Hajeri AAA, Farid EM, et al. Inherited CD59 deficiency, where neurology and genetics intertwine. Neurosciences (Riyadh). 2023 Apr;28(2):130-5.Full text Abstract
69. Gorevic PD. Rheumatoid factor, complement, and mixed cryoglobulinemia. Clin Dev Immunol. 2012;2012:439018.Full text Abstract
70. Levy Y, George J, Yona E, et al. Partial lipodystrophy, mesangiocapillary glomerulonephritis, and complement dysregulation. An autoimmune phenomenon. Immunol Res. 1998 Aug;18(1):55-60. Abstract
71. Corvillo F, Akinci B. An overview of lipodystrophy and the role of the complement system. Mol Immunol. 2019 Aug;112:223-32. Abstract
72. Prohászka Z, Nilsson B, Frazer-Abel A, et al. Complement analysis 2016: clinical indications, laboratory diagnostics and quality control. Immunobiology. 2016 Nov;221(11):1247-58. Abstract
73. Ling M, Murali M. Analysis of the complement system in the clinical immunology laboratory. Clin Lab Med. 2019 Dec;39(4):579-90. Abstract
74. Frazer-Abel A, Kirschfink M, Prohászka Z. Expanding horizons in complement analysis and quality control. Front Immunol. 2021 Aug 9;12:697313.Full text Abstract
75. Seelen MA, Roos A, Wieslander J, et al. Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA. J Immunol Methods. 2005 Jan;296(1-2):187-98. Abstract
76. Wehling C, Amon O, Bommer M, et al. Monitoring of complement activation biomarkers and eculizumab in complement-mediated renal disorders. Clin Exp Immunol. 2017 Feb;187(2):304-15.Full text Abstract
77. Germenis AE, Margaglione M, Pesquero JB, et al. International consensus on the use of genetics in the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2020 Mar;8(3):901-11. Abstract
78. Licht C, Weyersburg A, Heinen S, et al. Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15. Am J Kidney Dis. 2005 Feb;45(2):415-21. Abstract
79. Ricklin D, Mastellos DC, Reis ES, et al. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018 Jan;14(1):26-47.Full text Abstract
80. Mastellos DC, Ricklin D, Lambris JD. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov. 2019 Sep;18(9):707-29.Full text Abstract
81. Ricklin D. Complement-targeted therapeutics: are we there yet, or just getting started? Eur J Immunol. 2024 Dec;54(12):e2350816.Full text Abstract
82. West EE, Woodruff T, Fremeaux-Bacchi V, et al. Complement in human disease: approved and up-and-coming therapeutics. Lancet. 2024 Jan 27;403(10424):392-405.Full text Abstract
83. Greve J, Lochbaum R, Trainotti S, et al. The international HAE guideline under real-life conditions: from possibilities to limits in daily life - current real-world data of 8 German angioedema centers. Allergol Select. 2024;8:346-57.Full text Abstract
84. Betschel SD, Banerji A, Busse PJ, et al. Hereditary angioedema: a review of the current and evolving treatment landscape. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2315-25. Abstract
85. Aygören-Pürsün E, Zanichelli A, Cohn DM, et al. An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Lancet. 2023 Feb 11;401(10375):458-69. Abstract
86. Centers for Disease Control and Prevention. Vaccine recommendations and guidelines of the ACIP. General best practice guidelines for immunization: altered immunocompetence. Aug 2023 [internet publication].Full text
Use of this content is subject to our disclaimer