Evaluation of the interferon status in pregnant women with a high risk for infection complications


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Abstract

Subjects and methods. One hundred patients and their newborn infants were examined. Group 1 (a study group) consisted of 65 pregnant women with urogenital infection (UGI), including 24 with preterm birth (PB) and intrauterine infection (IUI) (Subgroup 1a), 15 with PB without IUI (Subgroup 1b), and 26 with term birth (Subgroup 1c). Group 2 (a control group) comprised 20 patients without IGI in whom pregnancy resulted in term birth. Group 3 (a comparison group) included 15 non-pregnant women. Cytokine gene expression in the peripheral cell mononuclear cells was determined using reverse-transcription polymerase chain reaction. A biological method was used to determine the elaboration of interferons (IFN) and the sensitivity of peripheral blood leukocytes (PBL) to IFN preparations. A patient was considered to be susceptible to IFN-α and IFN-γ if her PBLs responded by producing the higher levels of IFN during priming with at least one of the interferons. Results. The capacity to induce IFN-α production in the cultured leukocytes of pregnant women with PB was higher than that in healthy pregnant women (35.5±11.6 U/ml versus 25.5±5.4 U/ml). That to produce IFN-γ in the pregnant women with PB was, on the contrary, diminished (5.1±2.4 U/ml and 14.9±1.6 U/ml, respectively; р < 0.05). In pregnant women who gave birth prematurely, the ratio of induced IFN-α/IFN-γ production averaged 9.7±3.2 versus 3.2±1.4 in those who gave birth at term (p < 0.05). The induced IFN-α/IFN-γ production ratio more than 5 may be a prognostic factor for PB and fetal IUI. The positive prognostic value of this factor is 69%; its negative prognostic value is 85.7%; the sensitivity and specificity are 90 and 60%, respectively. In the pregnant women with PB, the high gene expression of IFN-α (82.3%) matches with its high elaboration in the cultured leukocytes (35.5±11.6 U/ml); however, with the high gene expression of IFN-γ (91.0%), its production is lowered (5.1±2.4 U/ml), suggesting impaired IFN-γ synthesis. PBLs in pregnant women with PB of infection genesis were noted to be highly sensitive to IFN preparations: Roferon A (82.0%) and Intron A (82.0%); in this case the sensitivity of cultured leukocytes to Gammaferon was found only in 20.5% of cases (p < 0.05). Conclusion. The risk factors of PB and fetal and neonatal IUI are UGI during pregnancy concurrent with chronic inflammatory diseases of small pelvic organs or chronic extragenital diseases. In the pregnant women with PB and high gene expression levels of IFN-γ, its production is lowered in the cultured leukocytes, which suggests impaired IFN-γ production at the post-transcriptional level. The induced PBL IFN-α/IFN-γ production ratio by 5 or more times allows PB to be predicted with a high degree of accuracy. The highest susceptibility (82.0%) to IFN-α preparations (Roferon A, Intron A) is shown by the leukocytes from pregnant women in the UGI and PB group, i.e. with the most pronounced changes in the interferon status.

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About the authors

I. V Bakhareva

N.I. Pirogov Russian National Research Medical University

Email: iribakhareva@yandex.ru
MD, professor, therapeutic faculty, 1st department of obstetrics and gynecology

L. V Gankovskaya

N.I. Pirogov Russian National Research Medical University

Email: gan@rsmu.ru
professor, Medicobiologic faculty, department of immunology

V. V Romanovskaya

N.I. Pirogov Russian National Research Medical University

Email: valentinaromano2005@yandex.ru
assistant of therapeutic faculty, 1st department of obstetrics and gynecology

M. V Mezentseva

Gamaleya Research Institute of Epidemiology and Microbiology

Email: marmez@mail.ru
head of the latent infection microbiology laboratory

A. M Magomedova

N.I. Pirogov Russian National Research Medical University

Email: amidoctor@mail.ru
assistant of therapeutic faculty, 1st department of obstetrics and gynecology

P. A Kuznetsov

N.I. Pirogov Russian National Research Medical University

Email: poohsmith@mail.ru
assistant of therapeutic faculty, 1st department of obstetrics and gynecology

V. V Grechenko

N.I. Pirogov Russian National Research Medical University

Email: v.grechenko@gmail.com
senior teacher of medicobiologic faculty, department of immunology

References

  1. Сухих Г.Т., Ванько Л.В. Иммунология беременности. М.: Издательство РАМН; 2003. [Sukhih G.T., Vanko L.V. Immunology of pregnancy. M.: Izdatelstvo RAMN; 2003. (In Russian)]
  2. Бахарева И.В., Ганковская Л.В., Ковальчук Л.В., Свитич О.А., Романовская В.В., Кузнецов П.А., Магомедова A.M., Дворецкая Е.В. Прогностическое значение экспрессии генов молекул врожденного иммунитета (TLR2, TLR4 и HBD1) при невынашивании беременности. Лечащий врач. 2012; 9: 84-90. [Bakhareva I.V., Gankovskaya L.V., Kovalchuk L.V., Svitich O.A., Romanovskaya V.V., Kuznetsov P.A., Magomedova A.M., Dvoretskaya E.V. Prognostic significance of gene expression of molecules of innate immunity (TLR2, TLR4 and HBD1) for miscarriage. Lechaschiy vrach. 2012; 9: 84-90. (In Russian)]
  3. Morin L., Lim K. Ultrasound in twin pregnancies. J. Obstet. Gynaecol. Can. 2011; 33(6): 643-56.
  4. Martin J.A., Kirmeyer S., Osterman M., Shepherd R.A. Born a bit too early: recent trends in late preterm births. NCHS Data Brief. 2009; 24: 1-8.
  5. Hamilton B.E., Martin J.A., Ventura S.J. Births: preliminary data for 2007. National Vital Statistics Reports. vol.57, no12. Hyattsville, MD: National Center for Health Statistics; Released March 18, 2009.
  6. Romero R., Miranda J., Chaiworapongsa T., Chaemsaithong P., Gotsch F., Dong Z. et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am. J. Reprod. Immunol. 2014; 71(4): 330-58.
  7. Сидельникова В.М., Антонов А.Г. Преждевременные роды. Недоношенный ребенок. Руководство для врачей. М.: ГЭОТАР-Медиа; 2006. 448 с. [Sidelnikova V.M., Antonov A.G. Premature birth. A premature baby. Guide for Physicians. M.: GEOTAR-Media; 2006. 448 p. (In Russian)]
  8. Сухих Г.Т., ред. Преждевременные роды. Методическое письмо. М.; 2011. [Suhih G.T., red. Premature birth. Methodological letter. M.; 2011. (In Russian)]
  9. Ганковская Л.В., Ковальчук Л.В., Бахарева И.В., Кузнецов П.А., Ганковская О.А., Романовская В.В., Карташов Д.Д., Макаров О.В. Экспрессия генов Toll-подобных рецепторов слизистой цервикального канала при нормальной и патологически протекающей беременности. Вестник Российского государственного медицинского университета. 2009; 4: 34-7. [Gankovskaya L.V., Kovalchuk L.V., Bahareva I.V., Kuznetsov P.A., Gankovskaya O.A., Romanovskaya V.V., Kartashov D.D., Makarov O.V. Gene expression of Toll-like receptors cervical mucosa in normal and diseased proceeding pregnancy. Vestnik Rossiyskogo gosudarstvennogo meditsinskogo universiteta. 2009; 4: 34-7. (In Russian)]
  10. Ananth C.V., Vintzileos A.M. Epidemiology of preterm birth and its clinical subtypes. J. Matern. Fetal Neonatal Med. 2006. 19(12): 773-82.
  11. Goldenberg R.L., Culhane J.F., Iams J.D., Romero R. Epidemiology and causes of preterm birth. Lancet. 2008; 371(9606): 75-84.
  12. Сухих Г.Т., Ванько Л.В. Иммунные механизмы в физиологии и патологии беременности. Иммунология. 2005; 9(2): 103-8. [Sukhih G.T., Vanko L.V. Immune mechanisms in the physiology and pathology of pregnancy. Immunologiya. 2005; 9(2): 103-8. (In Russian)]
  13. Сотникова Н.Ю., Анциферова Ю.С., Кудряшова А.В. Иммунологическая загадка беременности. Иваново; 2005. 276 с. [Sotnikova N.Yu., Antsiferova Yu.S., Kudryashova A.V. Immunological mystery of pregnancy. Ivanovo; 2005. 276 p. (In Russian)]
  14. Ковальчук Л.Г., Ганковская Л.В., Мешкова Р.Я. Клиническая иммунология и аллергология с основами общей иммунологии. М.: ГЭОТАР-Медиа; 2012. 640 с. [14.Kovalchuk L.G., Gankovskaya L.V., Meshkova R. Ya. Clinical immunology and allergology with basic immunology. M.: GEOTAR-Media; 2012. 640 p. (In Russian)]
  15. Beigi R.H., Yudin M.H., Cosentino L., Meyn L.A., Hillier S.L. Cytokines, pregnancy, and bacterial vaginosis: comparison of levels of cervical cytokines in pregnant and nonpregnant women with bacterial vaginosis. J. Infect. Dis. 2007; 196(9): 1355-60.
  16. Ганковская Л.В., Ковальчук Л.В., Ганковская О.А., Макаров О.В., Лавров В.Ф., Карташов Д.Д., Кузнецов П.А. Экспрессия противомикробных пептидов клетками слизистой оболочки цервикального канала и нейтрофилами периферической крови у беременных с урогенитальной инфекцией. Вестник Российского государственного медицинского университета. 2008; 5: 26-9. [Gankovskaya L.V., Kovalchuk L.V., Gankovskaya O.A., Makarov O.V., Lavrov V.F., Kartashov D.D., Kuznetsov P.A. Expression of antimicrobial peptides by cells of the mucous membrane of the cervical canal and peripheral blood neutrophils in pregnant women with urogenital infection. Vestnik Rossiyskogo gosudarstvennogo meditsinskogo universiteta. 2008; 5: 26-9. (In Russian)]
  17. Romero R., Espinoza J., Goncalves L.F., Kusanovic J.P., Friel L., Hassan S. The role of inflammation and infection in preterm birth. Semin. Reprod. Med. 2007; 25(1): 21-39.
  18. Кан Н.Е. Современные технологии в диагностике и прогнозировании внутриутробных инфекций: автореф. дис.. д-ра мед. наук. М.; 2005. [Kan N.E. Modern technology in the diagnosis and prognosis of intrauterine infections. Diss. M.; 2005. (In Russian)]
  19. Тетруашвили Н.К. Роль иммунных взаимодействий на ранних этапах физиологической беременности и при привычном выкидыше. Иммунология. 2008; 2: 124-9. [Tetruashvili N.K. The role of immune interactions in the early stages of physiological pregnancy and habitual abortion. Immunologiya. 2008; 2: 124-9. (In Russian)]
  20. Ершов Ф.И., Мезенцева М.В., Васильев А.Н., Щербенко В.Э., Наровлянский А.Н. Методические указания по проведению доклинических исследований цитокин-индуцирующей активности антивирусных препаратов. Ведомости научного центра экспертизы и государственного контроля лекарственных средств. 2002; 1: 26-9. [Ershov F.I., Mezentseva M.V., Vasilev A.N., Scherbenko V.E., Narovlyanskiy A.N. Methodological guidelines for conducting pre-clinical studies of cytokine-inducing activity of antiviral drugs. Vedomosti nauchnogo tsentra ekspertizyi i gosudarstvennogo kontrolya lekarstvennyih sredstv. 2002; 1: 26-9. (In Russian)]
  21. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinum thyocyoanate-phenol-chloroform extraction. Anal. Biochem. 1987; 162(1): 156-9.
  22. Gelder С.М., Thomas P.S., Yates D.H., Adcock I.M., Morrison J.F., Barnes PJ. Cytokine expression in normal, atopic, and asthmatic subject using the com bination of sputum induction and the polymerase chain reaction. Thorax. 1995; 50(10): 1033-7.
  23. Yamamura M., Uyemura K., Deans R.J., Weinberg K., Rea T.H., Bloom B.R., Modlin R.L. Defining protective responses pathogens: cytokine profiles in leprosy lesions. Science. 1991; 254(11): 277-9.
  24. Lin Y., Zhang M., Barnes P.F. Chemokine production by a human alveolar epithelial cell line in response to Mycobacterium tuberculosis.Infect. Immun. 1998; 66(3): 1121-6.
  25. Мезенцева М.В. Закономерности функционирования и направленная коррекция цитокиновой регуляторной сети: автореф. дис.. д-ра биол. наук. М.; 200 6. [Mezentseva M.V. Patterns of functioning and directed correction of cytokine regulatory network. Diss. M.; 2006. (In Russian)]
  26. Ершов Ф.И., Григорян С.С., Готовцева Е.П. Интерфероновый статус в норме и при различных заболеваниях. В кн.: Ершов Ф.И. Система интерферона в норме и при патологии. М.: Медицина; 1996: 135-46. [Ershov F.I., Grigoryan S.S., Gotovtseva E.P. Interferon status in health and in various diseases. In: Ershov F.I. Interferon system in health and disease. M.: Meditsina; 1996: 135-46. (In Russian)]

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