Kırım-Kongo Kanamalı Ateşinde Serum Alfa Defensin-1 Düzeylerinin Klinik Seyir ve Prognoz ile İlişkisi

Abstract

Amaç: Kırım-Kongo Kanamalı Ateşi (KKKA), ateş ve kanama ile seyreden zoonotik viral bir enfeksiyondur. Alfa defensin-1 (AD-1) antimikrobiyal bir proteindir. Bu çalışmanın amacı AD-1 düzeyleri ile KKKA’da klinik seyir ve prognoz arasındaki ilişkiyi araştırmak, aynı zamanda AD-1’in hastalığın patogenezindeki rolünü de incelemektir. Gereç ve Yöntemler: Bu çalışmaya KKKA tanısı almış olan ve Atatürk Üniversitesi Tıp Fakültesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Bölümünde yatarak takip edilen 50 hasta ve 38 sağlıklı kontrol dahil edildi. Serum AD-1 düzeyleri ELISA yöntemi ile ölçüldü ve gruplar arasında karşılaştırıldı. Bulgular: Hastalardaki serum AD-1 düzeyleri kontrol grubundan anlamlı şekilde daha yüksekti (p=0,017). Hastaların 18 (%36)’i ağır klinik seyir, 16 (%32)’sı orta düzeyde klinik seyir ve 16 (%32)’sı hafif klinik seyir olarak sınıflandırıldı. Serum AD-1 düzeyleri açısından bu üç grup arasında istatistiksel olarak anlamlı bir farklılık yoktu (p=0,729). Ortanca serum AD-1 seviyeleri, ölümcül vakalarda 171,0 (aralık, 126,8-221,2) ng/ml ve hayatta kalan hastalarda 118,7 (aralık, 91,9-183,3) ng/ml idi ve bu iki grup arasındaki bu farklılık istatistiksel olarak anlamlı idi (p=0,014). Sonuç: Sonuç olarak, KKKA hastalarında artan serum AD-1 düzeyleri ağır seyirli hastalarda ve ölümcül vakalarda daha da yüksek seyretmektedir. Bu sonuçlara dayalı olarak, AD-1'in klinik seyri gösterdiği ve mortalite hakkında faydalı bilgiler sağladığı görülmektedir. Bu konuda genellemeler yapabilmek için daha geniş çaplı araştırmalar yapılmalıdır.

Keywords

• alfa defensin-1
• Antimikrobiyal peptidler
• Kırım-Kongo Kanamalı Ateşi

The Relation Between Serum Alpha Defensin-1 Levels with Clinical Course and Prognosis in Crimean-Congo Hemorrhagic Fever

Abstract

Aim: Crimean-Congo Hemorrhagic Fever (CCHF) is a viral zoonotic infection characterized by fever and bleeding. Alpha-defensin-1 (AD-1) is an antimicrobial peptide. The aim of this study was to investigate the relationship between the clinical course and prognosis of CCHF and AD-1 serum levels, and also to examine the role of AD-1 in the pathogenesis of the disease. Material and Methods: Fifty patients diagnosed with CCHF and hospitalized at the Atatürk University Faculty of Medicine Department of Infectious Diseases and Clinical Microbiology, and 38 healthy control were included in this study. Serum AD-1 levels were measured using ELISA methods and compared between the groups. Results: Serum AD-1 levels in the patients were significantly higher than those in the control group (p=0.017). Of the patients, 18 (36%) were classified as severe clinical course, 16 (32%) as moderate clinical course, and 16 (32%) as mild clinical course. There was no statistically significant difference among the three groups in terms of serum AD-1 levels (p=0.729). Median serum AD-1 levels were 171.0 (range, 126.8-221.2) ng/ml in the fatal cases, and 118.7 (range, 91.9-183.3) ng/ml in the surviving patients, and the difference between these two groups was statistically significant (p=0.014). Conclusion: As a result, the increased serum AD-1 levels in CCHF patients, remained higher in severe course patients and in the fatal cases. On the basis of these results, AD-1 appears to indicate the clinical course and provide useful information about mortality. More extensive research should be performed to make generalizations on this subject.

Keywords

• Alpha defensın-1
• antimicrobial peptide
• Crimean-Congo Hemorrhagic Fever.

References

1. Shahid MF, Shabbir MZ, Ashraf K, Ali M, Yaqub S, Mukhtar N, et al. Seroprevalence of Crimean-Congo haemorrhagic fever among three selected risk human groups in disease-endemic region of Pakistan. Zoonoses Public Health. 2020;67(7):755-9.
2. Kerget F, Kerget B, Yılmaz İS. The association between procalcitonin, lactate level, and clinical prognosis in patients with Crimean-Congo hemorrhagic fever. Duzce Med J. 2021;23(3):299-304.
3. Ergönül O. Crimean-Congo haemorrhagic fever. Lancet Infect Dis. 2006;6(4):203-14.
4. Froy O. Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways. Cell Microbiol. 2005;7(10):1387-97.
5. Fellermann K, Stange EF. Defensins- innate immunity at the epithelial frontier. Eur J Gastroenterol Hepatol. 2001;13(7):771-6.
6. Jarczak J, Kościuczuk EM, Lisowski P, Strzałkowska N, Jóźwik A, Horbańczuk J, et al, Defensins: natural component of human innate immunity. Hum Immunol. 2013;74(9):1069-79.
7. Wilson SS, Wiens ME, Smith JG. Antiviral mechanisms of human defensins. J Mol Biol. 2013;425(24):4965-80.
8. Demirkhanyan LH, Marin M, Padilla-Parra S, Zhan C, Miyauchi K, Jean-Baptiste M, et al. Multifaceted mechanisms of HIV-1 entry inhibition by human α-defensin. J Biol Chem. 2012;287(34):28821-38.

9. Hazlett L, Wu M. Defensins in innate immunity. Cell Tissue Res. 2011;343(1):175-88.
10. Bagci B, Bagci G, Buyuktuna SA, Elaldi N. Association of MCP-1 promotor polymorphism with disease severity of Crimean-Congo hemorrhagic fever. J Med Virol. 2020;[Epub ahead of print]. doi: 10.1002/jmv.25790.
11. Bastian A, Schäfer H. Human alpha defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regul Pept. 2001;101(1-3):157-61.
12. Salvatore M, Garcia-Sastre A, Ruchala P, Lehrer RI, Chang T, Klotman ME. Alpha-defensin inhibits influenza virus replication by cell-mediated mechanism(s). J Infect Dis. 2007;196(6):835-43.
13. Hazrati E, Galen B, Lu W, Wang W, Ouyang Y, Keller MJ, et al. Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J Immunol. 2006;177(12):8658-66.
14. Buck CB, Day PM, Thompson CD, Lubkowski J, Lu W, Lowy DR, et al. Human alpha-defensins block papillomavirüs infection. Proc Natl Acad Sci USA. 2006;103(5):1516-21.
15. Smith JG, Silvestry M, Lindert S, Lu W, Nemerow GR, Stewart PL. Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog. 2010;6(6):e1000959.
16. Rapista A, Ding J, Benito B, Lo YT, Neiditch MB, Lu W, et al. Human defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment. Retrovirology. 2011;8:45.
17. Mumcu G, Cimilli H, Karacayli U, Inanc N, Ture-Ozdemir F, Eksioglu-Demiralp E, et al. Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet's disease. Arch Oral Biol. 2012;57(6):642-6.
18. Gunes M, Gecit I, Pirincci N, Kemik AS, Purisa S, Ceylan K, et al. Plasma human neutrophil proteins-1, -2, and -3 levels in patients with bladder cancer. J Cancer Res Clin Oncol. 2013;139(2):195-9.
19. Christensen HM, Frystyk J, Faber J, Schou M, Flyvbjerg A, Hildebrandt P, et al. α-Defensins and outcome in patients with chronic heart failure. Eur J Heart Fail. 2012;14(4):387-94.