Membrane attack complex of complement in pregnancy complicated by preeclampsia
https://doi.org/10.28996/2618-9801-2024-4-435-444
Abstract
Background: Recent studies have established a link between the development of preeclampsia (PE) and excessive activation or dysregulation of complement system. Investigating this system’s role may aid in the developing therapeutic strategies for treating PE.
Aims: To evaluate the levels of membrane attack complex (MAC) in blood serum during PE development in patients with chronic kidney disease (CKD) and the general population.
Materials and methods: The prospective observational study included 44 patients with PE: 17 women with a prior diagnosis of CKD and 27 women from the general population without a complicating somatic history. Soluble MAC levels was measured using an enzyme-linked immunoassay (HycultBiotech, Human Terminal Complement Complex Elisa Kit, HK32801).
Results: The incidence of mild and severe PE was similar between the groups. Among CKD patients, 29% (n=5) had mild PE and 71% (n=12) had severe PE, compared to 40% (n=11) and 60% (n=16), respectively. MAC levels were comparable between CKD and general population groups for mild PE (3933 [24676537] μU/ml vs 3202 [28134279] μU/ml [p=0.692]) and severe PE (4139 [38744458] μU/ml vs 4805 [32809594] μU/ml [p=0.378]), respectively. MAC levels did not differ significantly between mild and severe PE. In the general population, severe PE showed a trend toward higher MAC levels (4805 [32809594] μU/mL vs 3202 [28134279] μU/mL [p=0.054]). Severe PE was complicated by trombotiс microangiopathy (TMA) in 6 of 27 patients compared to 1 patient in the CKD group. Among patients with severe PE and TMA (7/44), MAC levels were significantly higher than in those without TMA (5345 [348713169] μU/ml vs 3933 [30574747] μU/ml [p=0.048]).
Conclusions: in PE patients, regardless of the development stage, severity or the presence CKD, MAC levels are elevated indicating hyperactivation of the complement system in this pregnancy complication. The highest MAC levels were observed in patients with TMA manifestations.
Keywords
About the Authors
N. L. KozlovskayaRussian Federation
6 Miklukho-Maklaya str., Moscow, 117198;
15/1 Lenskaya str., Moscow, 129327
M. V. Alekseeva
Russian Federation
6 Miklukho-Maklaya str., Moscow, 117198
K. A. Demyanova
Russian Federation
6 Miklukho-Maklaya str., Moscow, 117198;
15/1 Lenskaya str., Moscow, 129327
Yu. V. Korotchaeva
Russian Federation
15/1 Lenskaya str., Moscow, 129327;
8/2 Trubetskaya str., Moscow, 119048
S. V. Apresyan
Russian Federation
6 Miklukho-Maklaya str., Moscow, 117198;
15/1 Lenskaya str., Moscow, 129327
A. O. Lugovoy
Russian Federation
15/1 Lenskaya str., Moscow, 129327
A. R. Gabrielyan
Russian Federation
15/1 Lenskaya str., Moscow, 129327
P. V. Avdonin
Russian Federation
26 Vavilova str., 119334, Moscow
P. P. Avdonin
Russian Federation
26 Vavilova str., 119334, Moscow
References
1. Kassebaum NJ, Barber RM, Bhutta ZA et al. Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2015;388(10053):1775-1812. DOI: 10.1016/S0140-6736(16)31470-2
2. Derzsy Z, Prohaszka Z, Rigo JJr et al. Activation of the complement system in normal pregnancy and preeclampsia. Mol Immunol. 2010;47(7-8):1500-1506. DOI: 10.1016/j.molimm.2010.01.021
3. Lokki AI, Heikkinen-Eloranta J, Jarva H et al. Complement activation and regulation in preeclamptic placenta. Front Immunol. 2014;5:312. DOI: 10.3389/fimmu.2014.00312
4. Holmes CH, Simpson KL, Okada H et al. Complement regulatory proteins at the fetomaternal interface during human placental development: distribution of CD59 by comparison with membrane cofactor protein (CD46) and decay accelerating factor (CD55). Eur J Immunol. 1992;22(6):1579-1585. DOI: 10.1002/eji.1830220635
5. Girardi G, Yarilin D, Thurman JM et al. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med. 2006;203(9):2165-2175. DOI: 10.1084/jem.20061022
6. Yonekura Collier AR, Zsengeller Z, Pernicone E et al. Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia. Hypertens Preg. 2019;38(3):193-199. DOI: 10.1080/10641955.2019.1640725
7. Palomo M, Blasco M, Molina P et al. Complement activation and thrombotic microangiopathies. Clin J Am Soc Nephrol. 2019;14(12):1719-1732. DOI: 10.2215/CJN.05830519
8. Prakash J, Pant P, Prakash S et al. Changing picture of acute kidney injury in pregnancy: Study of 259 cases over a period of 33 years. Indian J Nephrol. 2016;26(4):262-267. DOI: 10.4103/0971-4065.161018
9. Ma Y, Kong LR, Ge Q et al. Complement 5a-mediated trophoblasts dysfunction is involved in the development of preeclampsia. J Cell Mol Med. 2018;22(2):1034-1046. DOI: 10.1111/jcmm.13466
10. Rampersad R, Barton A, Sadovsky Y, Nelson DM. The C5b-9 membrane attack complex of complement activation localizes to villous trophoblast injury in vivo and modulates human trophoblast function in vitro. Placenta. 2008;29(10):855-861. DOI: 10.1016/j.placenta.2008.07.008
11. Banadakoppa M, Balakrishnan M, Yallampalli C. Upregulation and release of soluble fms-like tyrosine kinase receptor 1 mediated by complement activation in human syncytiotrophoblast cells. Am J Reprod Immunol. 2018;80(5):e13033. DOI: 10.1111/aji.13033
12. Agostinis C, Stampalija T, Tannetta D et al. Complement component C1q as potential diagnostic but not predictive marker of preeclampsia. Am J Reprod Immunol. 2016;76(6):475-481. DOI: 10.1111/aji.12586
13. Lynch AM, Murphy JR, Gibbs RS et al. The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia. BJOG. 2010;117(4):456-462. DOI: 10.1111/j.1471-0528.2009.02473.x
14. Burwick RM, Velásquez JA, Valencia CM et al. Terminal complement activation in preeclampsia. Obstet Gynecol. 2018;132(6):1477-1485. DOI: 10.1097/AOG.0000000000002980
15. Wiles K, Bramham K, Seed PT et al. Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD. Kidney Int Rep. 2019;4(6):842-853. DOI: 10.1016/j.ekir.2019.03.012
16. Burwick RM, Fichorova RN, Dawood HY et al. Urinary excretion of C5b-9 in severe preeclampsia: tipping the balance of complement activation in pregnancy. Hypertension. 2013;62(6):1040-1045. DOI: 10.1161/HYPERTENSIONAHA.113.01420
17. Burwick RM, Togioka BM, Speranza RJ et al. Assessment of blood-brain barrier integrity and neuroinflammation in preeclampsia. Am J Obstet Gynecol. 2019;221(3):269.e1-269.e8.
18. Lokki AI, Heikkinen-Eloranta J. Pregnancy induced TMA in severe preeclampsia results from complement-mediated thromboinflammation. Human Immunology. 2021;82(5):371-378. DOI: 10.1016/j.humimm.2021.03.006
19. Luo ZC, An N, Xu HR et al. The effects and mechanisms of primiparity on the risk of pre-eclampsia: a systematic review. Paediatric and Perinatal Epidemiology. 2007;21(1):36-45. DOI: 10.1111/j.1365-3016.2007.00836.x
20. Dekker G, Sibai B. Primary, secondary, and tertiary prevention of preeclampsia. Lancet. 2001;357(9251):209-215. DOI: 10.1016/S0140-6736(00)03599-6
21. Bdolah Y, Elchalal U, Natanson-Yaron S et al. Relationship between nulliparity and preeclampsia may be explained by altered circulating soluble fms-like tyrosine kinase 1. Hypertension in Pregnancy. 2014;33(2):250-259. DOI: 10.3109/10641955.2013.858745
22. Saito S, Sakai M, Sasaki Y et al. Inadequate tolerance induction may induce pre-eclampsia. J Reprod Immunol. 2007;76(1-2):30-39. DOI: 10.1016/j.jri.2007.08.002
23. Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP syndrome. Placenta. 2013;34(2):201-203. DOI: 10.1016/j.placenta.2012.11.014
24. Kelly RJ, Höchsmann B, Szer J et al. Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2015;373(11):1032-1039. DOI: 10.1056/NEJMoa1502950
25. Hallstensen RF, Bergseth G, Foss S et al. Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn. Immunobiology. 2015;220(4):452-459. DOI: 10.1016/j.imbio.2014.11.003
26. Tan YC, Teo EC, Ng HJH. A Rare Case of Atypical Hemolytic Uremic Syndrome (aHUS) Precipitated by Dengue and the Treatment Landscape in Singapore. 2024;16(4):e58731. DOI: 10.7759/cureus.58731
Review
For citations:
Kozlovskaya N.L., Alekseeva M.V., Demyanova K.A., Korotchaeva Yu.V., Apresyan S.V., Lugovoy A.O., Gabrielyan A.R., Avdonin P.V., Avdonin P.P. Membrane attack complex of complement in pregnancy complicated by preeclampsia. Nephrology and Dialysis. 2024;26(4):435-444. (In Russ.) https://doi.org/10.28996/2618-9801-2024-4-435-444