Система комплемента: эволюция, функции и клиническое значение: ОБЗОРЫ

Родион Владимирович  Кораблев; Андрей Глебович  Васильев; Сарнг Саналович  Пюрвеев; Татьяна Викторовна  Брус; Александра Юрьевна  Пырх; Николай Сергоевич  Деданишвили; Мадина Башировна  Евлоева; Вероника Александровна  Труфакина

doi:10.56871/PED.2026.25.15.008

The complement system: evolution, functions and clinical significance

REVIEWS

Rodion V. Korablev Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0004-5754-8437
Andrey G. Vasiliev Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-8539-7128
Sarng S. Pyurveev Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine https://orcid.org/0000-0002-4467-2269
Tatyana V. Brus Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-7468-8563
Alexandra Yu. Pyrkh Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0001-4761-5076
Nikolai S. Dedanishvili Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-6231-445X
Madina B. Evloeva Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0003-1337-7026
Veronika A. Trufakina Pavlov First Saint Petersburg State Medical University https://orcid.org/0009-0007-1724-1977

Keywords:

complement system innate immunity opsonization membrane attack complex complementopathies atypical hemolytic uremic syndrome paroxysmal nocturnal hemoglobinuria hereditary angioedema система комплемента врожденный иммунитет опсонизация мембраноатакующий комплекс комплементопатии атипичный гемолитико-уремический синдром пароксизмальная ночная гемоглобинурия наследственный ангиоотек

Abstract

The evolution of complex defense systems has enabled mammals and other organisms to effectively resist pathogens. Homologs of complement proteins are found in primitive invertebrates and have been conserved throughout evolution. With the emergence of adaptive immunity in vertebrates, the complement system did not disappear and became more diverse due to the emergence of new components and functions. Different molecular patterns activate complement via three pathways, leading to target cell lysis. The classical pathway is mediated by antibodies, while the alternative and lectin pathways are not. In addition to its important role in innate immunity, the complement system is associated with adaptive immune responses, inflammation, the elimination of excess synapses during the development of the nervous system, and the proliferation and migration of certain progenitor cells. With the discovery of complement in various intracellular structures, data has emerged on its impact on metabolism, cell growth control, and cell survival. Dysregulation of the complement system underlies a number of diseases collectively termed "complementopathies". These include paroxysmal nocturnal hemoglobinuria, hereditary angioedema, and atypical hemolytic uremic syndrome. The pathogenesis of complementopathies is based on uncontrolled complement activation, which damages various intact cells due to decreased inhibitory effects caused by genetic defects. Therapeutic inhibition of certain complement components is an effective approach in patients with complementopathies. Complement system activity is assessed using tests of overall functional activity, determination of the concentration of individual components or antibodies to them, and genetic testing.

Author Biographies

Rodion V. Korablev, Saint Petersburg State Pediatric Medical University

MD, Ph D, Associate Professor, Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical University; address: 2 Litovskaya str., Saint Petersburg, 194100, Russia

Andrey G. Vasiliev, Saint Petersburg State Pediatric Medical University

MD, Ph D, Dr Med Sci, Professor, Head of the Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Sarng S. Pyurveev, Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

MD, Ph D, Associate Professor of the Department of Pathological Physiology with a course in Immunopathology; Head of the Interdepartmental Experimental Laboratory of the Departments of Pathophysiology, Normal Physiology and Medical Biophysics, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia; Researcher, Department of Pharmacology named after
S.V. Anichkov, Institute of Experimental Medicine, Saint Petersburg, Russia

Tatyana V. Brus, Saint Petersburg State Pediatric Medical University

MD, Ph D, Associate Professor of the Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Alexandra Yu. Pyrkh, Saint Petersburg State Pediatric Medical University

Assistant Professor, Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Nikolai S. Dedanishvili, Saint Petersburg State Pediatric Medical University

MD, Senior Laboratory Technician in the Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Madina B. Evloeva, Saint Petersburg State Pediatric Medical University

6th-year student of the Faculty of Preventive Medicine, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Veronika A. Trufakina, Pavlov First Saint Petersburg State Medical University

6th-year student of the Faculty of Medicine, Pavlov First State Medical University, Saint Petersburg, Russiaa

References

1. Nesargikar P.N., Spiller B., Chavez R. The complement system: history, pathways, cascade and inhibitors. Eur J Microbiol Immunol (Bp). 2012;2(2):103–111. https://doi.org/10.1556/Eu JMI.2.2012.2.2.

2. Ferrata A. Die Unwirksamkeit der komplexen Hämolysine in salzfreien Lösungen und ihre Ursache. Berlin Klin Wschr. 1907;44,366–375.

3. Pangburn M.K. Initiation of the alternative pathway of complement and the history of “tickover”. Immunol Rev. 2023;313(1):64–70. https://doi.org/10.1111/imr.13130.

4. Elvington M., Liszewski M.K., Atkinson J.P. Evolution of the complement system: from defense of the single cell to guardian of the intravascular space. Immunol Rev. 2016;274(1):9–15. https://doi.org/10.1111/imr.12474.

5. Jensen J.A., Festa E., Smith D.S., Cayer M. The complement system of the nurse shark: hemolytic and comparative characteristics. Science. 1981;214(4520):566–569. https://doi.org/10.1126/science.7291995.

6. Dobó J., Kocsis A., Farkas B., Demeter F., Cervenak L., Gál P. The Lectin pathway of the complement system — activation, regulation, disease connections and interplay with other (proteolytic) systems. Int J Mol Sci. 2024;25(3):1566. https://doi.org/10.3390/ijms25031566.

7. Gomez-Arboledas A., Acharya M.M., Tenner A.J. The Role of Complement in Synaptic Pruning and Neurodegeneration. Immunotargets Ther. 2021;10:373–386. https://doi.org/10.2147/ITT.S305420.

8. West E.E., Kemper C. Complosome — the intracellular complement system. Nat Rev Nephrol. 2023;19(7):426–439. https://doi.org/10.1038/s41581-023-00704-1.

9. Baines A.C., Brodsky R.A. Complementopathies. Blood Rev. 2017;31(4):213–223. https://doi.org/10.1016/j.blre.2017.02.003.

10. Gurevich E., Landau D. pharmacological management of atypical hemolytic uremic syndrome in pediatric patients: current and future. Paediatr Drugs. 2023;25(2):193–202. https://doi.org/10.1007/s40272-022-00555-6.

11. Панков Е.А., Папаян К.А., Савенкова Н.Д., Папаян Л.П., Капустин С.И. Атипичный гемолитико-уремический синдром у девочки 4 лет. Российский вестник перинатологии и педиатрии. 2017;62(4):187–188. EDN: ZFDAVZ.

12. Sinnathamby E.S., Issa P.P., Roberts L., Norwood H., Malone K., Vemulapalli H., Ahmadzadeh S., Cornett E.M., Shekoohi S., Kaye A.D. Hereditary Angioedema: diagnosis, clinical implications, and pathophysiology. Adv Ther. 2023;40(3):814–827. https://doi.org/10.1007/s12325-022-02401-0.