18Feb 2018

DISTURBED MATERNAL IMMUNE MILIEU EARLY IN PREGNANCY COULD PREDICT LATER DEVELOPMENT OF PRE-ECLAMPSIA AND DIFFERENTIATE ITS SEVERITY GRADES.

  • Departments of Obstetrics & Gynecology, Faculty of Medicine, Benha University.
  • Medical Biochemistry, Faculty of Medicine, Benha University.
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

Objectives: To estimate serum levels of tumor necrosis factor-? (TNF-?), interleukin (IL)-6 and IL-10 in primigravida women at the 12th week of gestation and to evaluate its predictability for later development and severity of pre-eclampsia (PE). Patients & Methods: The study included 130 primigravida women evaluated at the 12th week gestational age clinically to assure being normotensive and gave blood samples for ELISA estimation of serum levels of TNF-?, IL-6 and IL-10. All patients were evaluated 4-weekly for development of PE that was categorized as early or late and mild or severe. Results: Sixty-five women developed PE; 23 early PE and 42 late; 47 mild and 18 severe PE. Serum TNF-? and IL-6 levels were significantly higher, while serum IL-10 levels were significantly lower in PE than control women with significantly higher IL-6/IL-10 ratio in PE women. ROC curve analysis defined high body weight, body mass index, high serum IL-6 and TNF-? and high IL-6/IL-10 ratio as significant specific predictor, while low serum IL-10 as a significant sensitive predictor for possibility of development of PE. Also, ROC curve analysis defined high IL-6/IL-10 ratio as significant sensitive predictor for severe PE, while defined high serum IL-6 and high TNF-? as significant specific predictors for mild PE. Conclusion: Pre-eclampsia was associated with shift of immune response to pregnancy towards production of pro-inflammatory cytokines. The detected early disturbance of immune milieu points to its role in pathogenesis of PE. High IL-6/IL-10 ratio early in pregnancy could predict later development of PE especially severe PE. High IL-6 and TNF-? serum levels could early predict the development of mild PE.


  1. Jeyabalan A: Epidemiology of?preeclampsia: impact of?obesity. Nutr Rev.?2013; 71 Suppl 1:S18-25.
  2. Phipps E,?Prasanna D,?Brima W,?Jim B: Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines. Clin J Am Soc Nephrol.?2016; 11(6):1102-13.
  3. Ahmed A, Rezai H, Broadway-Stringer S: Evidence-Based Revised View of the Pathophysiology of Preeclampsia. Adv Exp Med Biol.?2017;956:355-374.
  4. Smith TA, Kirkpatrick DR, Kovilam O, Agrawal DK: Immunomodulatory role of vitamin D in the pathogenesis of preeclampsia. Expert Rev Clin Immunol. 2015; 11(9):1055-63.
  5. Cheng SB, Sharma S: Interleukin-10: a pleiotropic regulator in pregnancy. Am J Reprod Immunol. 2015; 73(6):487-500.
  6. Laresgoiti-Servitje E: A leading role for the immune system in the pathophysiology of preeclampsia. J Leukoc Biol. 2013; 94(2):247-57.
  7. Cardaropoli S, Rolfo A, Todros T: Helicobacter pylori and pregnancy-related disorders. World J Gastroenterol. 2014; 20(3):654-64.
  8. Konečn? B, Vlkov? B, Celec P: Role of fetal DNA in preeclampsia (review). Int J Mol Med. 2015; 35(2):299-304.
  9. Cray C, Zaias J, Altman NH: Acute phase response in animals: a review. Comp Med., 2009; 59(6): 517-26.
  10. Kraj P,?Ignatowicz L: The mechanisms shaping the repertoire of CD4+ Foxp3+?regulatory T cells. Immunology.?2018 Mar; 153(3):290-296.
  11. Ng SC, Gilman-Sachs A, Thaker P, Beaman KD, Beer AE, Kwak-Kim J: Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. Am J Reprod Immunol. 2002; 48(2):77-86.
  12. Pinheiro MB, Gomes KB, Ronda CR, Guimar?es GG, Freitas LG, Teixeira-Carvalho A, Martins-Filho OA, Dusse LM: Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population. Cytokine. 2015; 71(2):232-7.
  13. Wang J, Su L, Zhu T: [Effect of dendritic cells on the differentiation of Th1/Th17 in peripheral blood from preeclampsia patients]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013 Jul;29(7):744-7.
  14. Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S, Dolaptchieva M, Alexander T, Taran A, Malfertheiner SF, Costa SD, Zimmermann G, Nitschke C, Volk HD, Alexander H, Gunzer M, Zenclussen AC: Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J Immunol. 2009; 182(9):5488-97.
  15. Duan H, Zhao G, Xu B, Hu S, Li J: Maternal Serum PLGF, PAPPA, β-hCG and AFP Levels in Early Second Trimester as Predictors of Preeclampsia. Clin Lab. 2017 May 1;63(5):921-925.
  16. Gifford RW, August PA, Cunningham FG: Report of the national high blood pressure working group on research on hypertension in pregnancy. Am. J Obstet. Gynecol., 2000; 183:S1?22.
  17. Lenfant C; National Education Program Working Group on High Blood Pressure in Pregnancy: Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich). 2001; 3(2):75-88.
  18. Practice Bulletin No. 33: Diagnosis and management of preeclamp?sia and eclampsia. Obstetrics and Gynecology, 2002; 99: 159?67
  19. Poll T: IL-10 release during endotoxaemia in chimpanzees: role of platelet-activating factor and IL-6. Scand. J Immunol. 1996; 43: 122
  20. Gaines-Das RE, Poole S: The international standard for interleukin-6?evaluation in an international collaborative study. J Immunol Methods. 1993; 160: 147?53.
  21. De Kossodo S, Houba V, Grau GE: the WHO Collaborative Study Group. Assaying tumor necrosis factor concentrations in human serum. A WHO international collaborative study. J Immunol Methods. 1995; 182:107?14.
  22. Vargas-Rojas MI, Solleiro-Villavicencio H, Soto-Vega E: Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia. J Matern Fetal Neonatal Med. 2016; 29(10):1642-5.
  23. Cornelius DC, Amaral LM, Wallace K, Campbell N, Thomas AJ, Scott J, Herse F, Wallukat G, Dechend R, LaMarca B: Reduced uterine perfusion pressure T-helper 17 cells cause pathophysiology associated with preeclampsia during pregnancy. Am J Physiol Regul Integr Comp Physiol. 2016; 311(6):R1192-9.
  24. Zhang Z, Liu H, Shi Y, Xu N, Wang Y, Li A, Song W: Increased circulating Th22 cells correlated with Th17 cells in patients with severe preeclampsia. Hypertens Pregnancy. 2017; 36(1):100-107.
  25. Ribeiro VR, Romao-Veiga M, Romagnoli GG, Matias ML, Nunes PR, Borges VTM, Peracoli JC, Peracoli MTS: Association between cytokine profile and transcription factors produced by T-cell subsets in early- and late-onset pre-eclampsia. Immunology. 2017; 152(1):163-173.
  26. Poordast T, Najib FS, Baharlou R, Bijani A, Alamdarloo SM, Poordast A: Assessment of T helper 17-associated cytokines in third trimester of pregnancy. Iran J Immunol. 2017; 14(2):172-179.
  27. Xu J2, Gu Y, Sun J, Zhu H, Lewis DF, Wang Y: Reduced CD200 expression is associated with altered Th1/Th2 cytokine production in placental trophoblasts from preeclampsia. Am J Reprod Immunol. 2018; 79(1). doi: 10.1111/aji.12763.
  28. Salazar Garcia MD, Mobley Y, Henson J, Davies M, Skariah A, Dambaeva S, Gilman-Sachs A, Beaman K, Lampley C, Kwak-Kim J: Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia. J Reprod Immunol. 2018; 125:25-31.
  29. Daneva AM, Had?i-Lega M, Stefanovic M: Correlation of the system of cytokines in moderate and severe preeclampsia. Clin Exp Obstet Gynecol. 2016;43(2):220-4.
  30. Wang?J,?Tao YM,?Cheng XY,?Zhu TF,?Chen ZF,?Yao H,?Su LX: Dendritic cells?derived from?preeclampsia?patients influence Th1/Th17 cell differentiation in vitro. Int J Clin Exp Med.?2014; 7(12):5303-9
  31. Kemse N, Sundrani D, Kale A, Joshi S: Maternal Micronutrients, Omega-3 Fatty Acids and Gene Expression of Angiogenic and Inflammatory Markers in Pregnancy Induced Hypertension Rats. Arch Med Res. 2017; 48(5):414-422.
  32. Fan DM, Wang Y, Liu XL, Zhang A, Xu Q: Polymorphisms in interleukin-6 and interleukin-10 may be associated with risk of preeclampsia. Genet Mol Res. 2017;16(1).
  33. Scroggins SM, Santillan DA, Lund JM, Sandgren JA, Krotz LK, Hamilton WS, Devor EJ, Davis HA, Pierce GL, Gibson-Corley KN, Sigmund CD, Grobe JL, Santillan MK: Elevated Vasopressin in Pregnant Mice Induces T Helper Subset Alterations Consistent with Human Preeclampsia. Clin Sci (Lond). 2018 Jan 25. pii: CS20171059. doi: 10.1042/CS20171059. [Epub ahead of print]

[Amr Sharafeldeen and Shaymaa M Abd El-Rahman. (2018); DISTURBED MATERNAL IMMUNE MILIEU EARLY IN PREGNANCY COULD PREDICT LATER DEVELOPMENT OF PRE-ECLAMPSIA AND DIFFERENTIATE ITS SEVERITY GRADES. Int. J. of Adv. Res. 6 (Feb). 1107-1116] (ISSN 2320-5407). www.journalijar.com


Amr Sharaf El-Deen
Departments of Obstetrics & Gynecology, Faculty of Medicine, Benha University.

DOI:


Article DOI: 10.21474/IJAR01/6535      
DOI URL: https://dx.doi.org/10.21474/IJAR01/6535