Kazan medical journal

Казанский медицинский журнал

0368-48142587-9359

Eco-Vector

2009

10.17816/KMJ2009

Hot issues of infectious deseases

Актуальные вопросы инфекционной патологии

Research Article

Neopterin - a potential diagnostic and prognostic marker in infection diseases

Неоптерин - потенциальный диагностический и прогностический маркёр при инфекционных заболеваниях

Dudina

K R

Дудина

Кристина Рубеновна

dudinakr@mail.ru

Kutateladze

M M

Кутателадзе

Марина Михайловна

Znoiko

O O

Знойко

Ольга Олеговна

Bokova

N O

Бокова

Наталья Олеговна

Shutko

S A

Шутько

Светлана Анатольевна

Kozina

A N

Козина

Анастасия Николаевна

Ogarev

V V

Огарёв

Валерий Владимирович

Yushchuk

N D

Ющук

Николай Дмитриевич

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, RussiaМосковский государственный медико-стоматологический университет им. А.И. Евдокимова

15122014

956

VOL 95, NO6 (2014)

ТОМ 95, №6 (2014)

93894328032016

2014

Dudina K.R., Kutateladze M.M., Znoiko O.O., Bokova N.O., Shutko S.A., Kozina A.N., Ogarev V.V., Yushchuk N.D.

Дудина К.Р., Кутателадзе М.М., Знойко О.О., Бокова Н.О., Шутько С.А., Козина А.Н., Огарёв В.В., Ющук Н.Д.

http://creativecommons.org/licenses/by-nc-sa/4.0

https://kazanmedjournal.ru/kazanmedj/article/view/2009

Clinical significance of determining the neopterin concentration in body fluids is reviewed. The results of researches on determining the neopterin concentrations in various infectious diseases (vector-borne diseases, herpes, respiratory and intestinal infections, as well as human immunodeficiency virus infection) conducted over the past 2 years are discussed. Neopterin is a biologically stable metabolite, which gives an advantage of its detection to assess the activity of the immune response. Previously neopterin was determined mainly by high-performance liquid chromatography. In recent years, enzyme-linked immunosorbent assay was introduced and frequently used for determining neopterin concentrations. It was shown that neopterin concentrations can vary also in the absence of the pathological process. In particular, some general factors such as race, age, body mass index, smoking and arterial pressure may influence on the concentrations of neopterin in the human body. Increased level of neopterin in body biological fluids and the kynurenine/tryptophan ratio are measured in diseases involving interferon-γ-mediated immune response activation. In this regard, the highest concentrations of neopterin and increased kynurenine/tryptophan ratio are observed in cases of infectious diseases, malignancies, transplant rejection, a number of cardiovascular and autoimmune diseases. It was shown that neopterin can be regarded as a highly specific marker of viral infection, and its blood concentration reflect the prognosis of the disease. Monitoring neopterin level may be useful to assess the severity and activity of an infectious disease, its clinical course, and to control the effectiveness of etiological treatment for many infectious diseases.

Освещено клиническое значение определения концентрации неоптерина в биологических жидкостях. Проанализированы результаты научных исследований, посвящённых определению концентраций неоптерина при инфекционных заболеваниях различной этиологии (таких, как трансмиссивные заболевания, герпетические, респираторные и кишечные инфекции, а также инфекция, обусловленная вирусом иммунодефицита человека) за последние 20 лет. Неоптерин - биологически устойчивый метаболит, что свидетельствует о преимуществе его определения для оценки активности иммунного ответа. Ранее неоптерин определяли в основном с помощью высокоэффективной жидкостной хроматографии. В последние годы для анализа концентрации неоптерина чаще применяют твердофазный иммуноферментный анализ. Установлено, что концентрации неоптерина могут варьировать и при отсутствии патологического процесса. В частности, на концентрацию неоптерина в организме человека могут оказывать влияние такие общие факторы, как раса, возраст, индекс массы тела, курение и артериальное давление. Повышение уровня неоптерина в биологических средах организма и соотношение кинуренин/триптофан регистрируют при заболеваниях, сопровождающихся активацией опосредованного интерфероном γ иммунного ответа. В связи с этим наиболее высокие концентрации неоптерина и повышение соотношения кинуренин/триптофан отмечают при инфекционных болезнях, злокачественных новообразованиях, отторжении трансплантата, ряде сердечно-сосудистых и аутоиммунных заболеваний. Показано, что неоптерин можно рассматривать как высокоспецифичный маркёр вирусной инфекции, а его концентрации в крови отражают прогноз течения заболевания. Мониторирование уровня неоптерина может быть полезным для оценки степени тяжести и активности инфекционного заболевания, динамики его течения, а также для контроля эффективности этиотропной терапии при многих заболеваниях инфекционной природы.

neopterininfectious diseases

неоптерининфекционные заболевания

Akbulut H.H., Celik I., Akbulut A. et al. Serum neopterin levels in patients with brucellosis // J. Infect. - 2005. - Vol. 51, N 4. - P. 281-286.

Babb K., Carrington C.V., Monteil M.A. A preliminary study of neopterin as a potential marker for severe dengue virus infection // Trans. R. Soc. Trop. Med. Hyg. - 1999. - Vol. 93, N 4. - P. 447-448.

Baier-Bitterlich G., Wachter H., Fuchs D. Role of neopterin and 7,8-dihydroneopterin in human immunodeficiency virus infection: marker for disease progression and pathogenic link // J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. - 1996. -Vol. 13, N 2. - P. 184-193.

Baize S., Leroy E.M., Georges A.J. et al. Inflammatory responses in Ebola virus-infected patients // Clin. Exp. Immunol. - 2002. - Vol. 128, N 1. - P. 163-168.

Bellmann-Weiler R., Schroecksnadel K., Holzer C. et al. IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein Barr virus-infection // J. Affect Disord. - 2008. - Vol. 108, N 1-2. - P. 171-176.

Bociąga-Jasik M., Cieśla A., Kalinowska-Nowak A. et al. Role of IL-6 and neopterin in the pathogenesis of herpetic encephalitis // Pharmacol. Rep. - 2011. - Vol. 63, N 5. - P. 1203-1209.

Brown A.E., Webster H.K., Teja-Isavadharm P., Keeratithakul D. Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma // Clin. Exp. Immunol. - 1990. - Vol. 82, N 1. - P. 97-101.

Cakan G., Bezirci F.B., Kacka A. et al. Assessment of diagnostic enzyme-linked immunosorbent assay kit and serological markers in human brucellosis // Jpn. J. Infect. Dis. - 2008. - Vol. 61, N 5. - P. 366-370.

Capuron L., Geisler S., Kurz K. et al. Activated immune system and inflammation in healthy ageing: relevance for tryptophan and neopterin metabolism // Curr. Pharm. Des. - 2014. - Vol. 20, N 38. - P. 6048-6057.

10.

Chadha S., Bhalla P., Gautam H. et al. Utility of serum neopterin and serum il-2 receptor levels to predict absolute CD4 T-lymphocyte count in HIV infected cases // Interdiscip. Perspect. Infect. Dis. - 2013. - doi: 10.1155/2013/143648. - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870075/ (дата обращения: 01.10.14).

11.

Chan C.P., Choi J.W., Cao K.Y. et al. Detection of serum neopterin for early assessment of dengue virus infection // J. Infect. - 2006. - Vol. 53, N 3. - P. 152-158.

12.

Chatelet P., Hautecoeur P., Dhondt J.L. et al. Unconjugated pteridines and neuromeningeal infections // Rev. Neurol. (Paris). - 1993. - Vol. 149, N 5. - P. 331-335.

13.

Cok G., Parildar Z., Basol G. et al. Pleural fluid neopterin levels in tuberculous pleurisy // Clin. Biochem. - 2007. - Vol. 40, N 12. - P. 876-880.

14.

Demirturk N., Demirdal T., Aktepe O.C. et al. Serum neopterin levels in patients with HBV infection at various stages // Hepatogastroenterology. - 2007. - Vol. 54, N 75. - P. 903-905.

15.

Denz H., Fuchs D., Hausen A. et al. Value of urinary neopterin in the differential diagnosis of bacterial and viral infections // Klinische Wochenschrift. - 1990. - Vol. 68, N 4. - P. 218-222.

16.

Frick B., Schroecksnadel K., Neurauter G. et al. Increasing production of homocysteine and neopterin and degradation of tryptophan with older age // Clin. Biochem. - 2004. - Vol. 37, N 8. - P. 684-687.

17.

Fuchs D., Stahl-Hennig C., Gruber A. et al. Neopterin-its clinical use in urinalysis // Kidney Int. - 1994. - Vol. 47. - P. 8-11.

18.

Girgin G., Sahin T.T., Fuchs D. et al. Tryptophan degradation and serum neopterin concentrations in intensive care unit patients // Toxicol. Mech. Methods. - 2011. - Vol. 21, N 3. - P. 231-235.

19.

Halota W., Jaruga B., Pawłowska M. Serum neopterin and beta2-microglobulin concentration as «prognostic markers» of AIDS // Pol. Merkur. Lekarski. - 2002. - Vol. 13, N 74. - P. 126-128.

20.

Hamerlinck F.F., van Gool T., Faber W.R., Kager P.A. Serum neopterin concentrations during treatment of leishmaniasis: useful as test of cure? // FEMS Immunol. Med. Microbiol. - 2000. - Vol. 27, N 1. - P. 31-34.

21.

Immanuel C., Victor L., Chelvi K.S. et al. Serum neopterin levels in HIV infected patients with & without tuberculosis // Indian J. Med. Res. - 2005. - Vol. 121. - P. 220-225.

22.

Inci Fisenk B., Us D., Ozcebe O.I., Hascelik G. The value of increased neopterin levels in reducing transfusion-transmitted virus infections: detection of a donation from a HBSAg positive chronic carrier by screening of neopterin in Turkish blood donors // Scand. J. Infect. Dis. - 2005. - Vol. 37, N 8. - P. 599-604.

23.

Ip M., Rainer T.H., Lee N. et al. Value of serum procalcitonin, neopterin, and C-reactive protein in differentiating ba cterial from viral etiologies in patients presenting with lower respiratory tract infections // Diagn. Microbiol. Infect. Dis. - 2007. - Vol. 59, N 2. - P. 131-136.

24.

Jungraithmayr T.C., Reschke M., Grebe S.O. et al. Assessment of cytomegalovirus infections using neopterin and a new immunoblot // Clin. Chim. Acta. - 2001. - Vol. 310, N 1. - P. 63-69.

25.

Kaleli I., Demir M., Cevahir N. et al. Serum neopterin levels in patients with replicative and nonreplicative HBV carriers // BMC Infect. Dis. - 2006. - Vol. 6. - P. 157. - doi:10.1186/1471-2334-6-157.

26.

Kalkan A., Ozden M., Akbulut H. Serum neopterin levels in patients with chronic hepatitis B // Jpn. J. Infect. Dis. - 2005. - Vol. 58, N 2. - P. 107-109.

27.

Kandelaki E.T., Nemsadze K.P., Chkhaidze I.G. et al. Neopterine and ige during respiratory-syncytial virus infection in infants // Georgian Med. News. - 2006. - Vol. 130. - P. 76-80.

28.

Kiliç D., Boyunağa H., Kaygusuz S. et al. Neopterin levels in nonreplicative HBV carriers // Hepatol. Res. - 2002. - Vol. 24, N 1. - P. 18.

29.

Kitchen M., Quigley M.A., Mwinga A.M. et al. HIV progression and predictors of mortality in a community-based cohort of Zambian adults // J. Int. Assoc. Physicians AIDS Care (Chic). - 2008. - Vol. 7, N 1. - P. 17-26.

30.

Kozłowska-Murawska J., Obuchowicz A.K. Clinical usefulness of neopterin // Wiad. Lek. - 2008. - Vol. 61, N 10-12. - P. 269-272.

31.

Kremsner P.G., Winkler S., Wildling E. et al. High plasma levels of nitrogen oxides are associated with severe disease and correlate with rapid parasitological and clinical cure in Plasmodium falciparum malaria // Trans. R. Soc. Trop. Med. Hyg. - 1996. - Vol. 90, N 1. - P. 44-47.

32.

Ledochowski M., Murr C., Widner B., Fuchs D. Association between insulin resistance, body mass and neopterin concentrations // Clin. Chim. Acta. - 1999. - Vol. 282, N 1-2. - P. 115-123.

33.

Łuczak G., Plata-Nazar K., Kozielska E. et al. Serum neopterin level in children with lower respiratory tract infections // Med. Wieku Rozwoj. - 2007. - Vol. 11, N 4. - P. 423-427.

34.

Mildvan D., Spritzler J., Grossberg S.E. et al. Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection // Clin. Infect. Dis. - 2005. - Vol. 40, N 6. - P. 853-858.

35.

Murr C., Widner B., Wirleitner B., Fuchs D. Neopterin as a marker for immune system activation // Curr. Drug Metabol. - 2002. - Vol. 3. - P. 175-187.

36.

Nyamweya S., Townend J., Zaman A. et al. Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections? // PLoS One. - 2012. - Vol. 7, N 9. - e44411. - doi: 10.1371/journal.pone.0044411.

37.

Onguru P., Akgul E.O., Akinci E. et al. High serum levels of neopterin in patients with Crimean-Congo hemorrhagic fever and its relation with mortality // J. Infect. - 2008. - Vol. 56, N 5. - P. 366-370.

38.

Panero L.A., Nogales E.A. Neopterin as marker of immunologic activation in viral and bacterial infections // An. Esp. Pediatr. - 1996. - Vol. 45, N 6. - P. 597-602.

39.

Pingle S.K., Tumane R.G., Jawade A.A. Neopterin: biomarker of cell-mediated immunity and potent usage as biomarker in silicosis and other occupational diseases // Indian J. Occup. Environ Med. - 2008. - Vol. 12, N 3. - P. 107-111.

40.

Ploder M., Spittler A., Kurz K. et al. Accelerated tryptophan degradation predicts poor survival in trauma and sepsis patients // Int. J. Tryptophan. Res. - 2010. - Vol. 3. - P. 61-67.

41.

Richardson K., Weinberg A. Dynamics of regulatory T-cells during pregnancy: effect of HIV infection and correlations with other immune parameters // PLoS One. - 2011. - Vol. 6, N 11. - e28172. - doi: 10.1371/journal.pone.0028172.

42.

Schennach H., Hessenberger G., Mayersbach P. et al. Acute cytomegalovirus infections in blood donors are indicated by increased serum neopterin concentrations // Med. Microbiol. Immunol. - 2002. - Vol. 191, N 2. - P. 115-118.

43.

Schennach H., Lanthaler A.J., Mayersbach P. et al. Human parvovirus Bb19 detection in asymptomatic blood donors: association with increased neopterin concentrations // J. Infect. Dis. - 2002. - Vol. 186, N 10. - P. 1494-1497.

44.

Schennach H., Murr C., Gächter E. et al. Factors influencing serum neopterin concentrations in a population of blood donors // Clin. Chem. - 2002. - Vol. 48, N 4. - P. 643-645.

45.

Schennach H., Schoenitzer D., Fuchs D. Association between chronic hepatitis C virus infection and increased neopterin concentrations in blood donations // Clin. Chem. - 1998. - Vol. 44, N 10. - P. 2225-2226.

46.

Schoenborn J.R., Wilson C.B. Regulation of interferon-gamma during innate and adaptive immune responses // Adv. Immunol. - 2007. - Vol. 96. - P. 41-101.

47.

Schriefer A., Barral A., Carvalho E.M., Barral-Netto M. Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis // Clin. Exp. Immunol. - 1995. - Vol. 102, N 3. - P. 535-540.

48.

Schröcksnadel K., Wirleitner B., Winkler C., Fuchs D. Monitoring tryptophan metabolism in chronic immune activation // Clin. Chim. Acta. - 2006. - Vol. 364, N 1-2. - P. 82-90.

49.

Schroecksnadel K., Sarcletti M., Winkler C. et al. Quality of life and immune activation in patients with HIV-infection // Brain Behav. Immun. - 2008. - Vol. 22, N 6. - P. 881-889.

50.

Shestakova I.V., Iushchuk N.D., Andreev I.V. et al. Development of immunopathology in patients with yersinia infection // Ter. Arkh. - 2005. - Vol. 77, N 11. - P. 7-10.

51.

Singh K.K., Wan-Nurfahizul-Izzati W., Ismail A. Serum neopterin is elevated in patients infected with Shigella // Gut. Pathogens. - 2010. - Vol. 2. - P. 9. - doi:10.1186/1757-4749-2-9.

52.

Turgut T., Akbulut H., Deveci F. et al. Serum interleukin-2 and neopterin levels as useful markers for treatment of active pulmonary tuberculosis // Tohoku J. Exp. Med. - 2006. - Vol. 209, N 4. - P. 321-328.

53.

Winkler C., Schroecksnadel K., Moheno P. et al. Calcium-pterin suppresses mitogen-induced tryptophan degradation and neopterin production in peripheral blood mononuclear cells // Immunobiology. - 2006. - Vol. 211, N 10. - P. 779-784.

54.

Wirleitner B., Schroecksnadel K., Winkler C., Fuchs D. Neopterin in HIV-1 infection // Mol. Immunol. - 2005. - Vol. 42, N 2. - P. 183-194.

55.

Yilmaz A., Yiannoutsos C.T., Fuchs D. et al. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy // Neuroinflammation. - 2013. - Vol. 10. - P. 62. - doi: 10.1186/1742-2094-10-62.

56.

Yuksekol I., Ozkan M., Akgul O. et al. Urinary neopterin measurement as a non-invasive diagnostic method in pulmonary tuberculosis // Int. J. Tuberc. Lung Dis. - 2003. - Vol. 7, N 8. - P. 771-776.

57.

Zeller J.M., McCain N.L, Swanson B. Immunological and virological markers of HIV-disease progression // J. Assoc. Nurses AIDS Care. - 1996. - Vol. 7, N 1. - P. 15-27.

58.

Zheng B., Cao K.Y., Chan C.P. et al. Serum neopterin for early assessment of severity of severe acute respiratory syndrome // Clin. Immunol. - 2005. - Vol. 116, N 1. - P. 18-26.

59.

Zwirska-Korczala K., Dziambor A.P., Wiczkowski A. et al. Hepatocytes growth factor (HGF), leptin, neopterin serum concentrations in patients with chronic hepatitis C // Przegl. Epidemiol. - 2001. - Vol. 55, N 3. - P. 164-169.