Thrombocytopenia in Patients with Dengue Virus Infection and Correlation between Circulating Soluble MICB Protein Level and Platelet Counts

Le Van Tuan^1, , Phan Thi Tuyet Nga¹, Trinh Thi Hong Hanh¹, Nguyen Thi Thu Tram¹ and Pham Tho Duoc¹

¹Department of Virology, Tay Nguyen Institute of Hygiene and Epidemiology, Buon Ma Thuot city, DakLak, Vietnam

Cite this paper:
Le Van Tuan, Phan Thi Tuyet Nga, Trinh Thi Hong Hanh, Nguyen Thi Thu Tram and Pham Tho Duoc. Thrombocytopenia in Patients with Dengue Virus Infection and Correlation between Circulating Soluble MICB Protein Level and Platelet Counts. American Journal of Infectious Diseases and Microbiology. 2017; 5(2):74-79. doi: 10.12691/ajidm-5-2-1

Abstract

Background: Soluble MHC class I polypeptide-related sequence B (sMICB) has been associated with the development of severity of dengue fever. However, serum sMICB level and relationship with platelets in patients with dengue virus (DENV) infection remain unclear. The aims of this study are to identify soluble MICB serum level and the correlation with platelets counts in patients with dengue virus infection. Methods: A total of 88 patients were confirmed with an acute phase of DENV infection (1–7 days after the onset of illness) based on the result a positive reverse transcriptase-polymerase chain reaction (RT-PCR), or anti-dengue IgM antibodies were used. Serum soluble MICB level was measured by MICB ELISA. Results: Serum soluble MICB (sMICB) levels in dengue virus infected patients were observed a median of 146.3 pg/ml. Serum sMICB was significantly higher in dengue patients with warning signs and severe compared to patients without warning signs. However, no significant difference of sMICB between age groups of dengue patients; and between primary and secondary infection were observed (P > 0.05). The significantly negative correlation between serum sMICB levels and platelet counts was found (Spearman’s rho = -0.34, P = 0.001). Conclusion: Serum sMICB levels might be considered as a potential prognostic biomarker for dengue patients.

Keywords:
dengue fever dengue virus infection soluble MHC class I polypeptide-related sequence B

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References:

[1]	WHO: Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Hemorrhagic Fever. Revised and expanded edition New Delhi, India 2011:11-16.
[2]	Martina BE, Koraka P, Osterhaus AD: Dengue virus pathogenesis: an integrated view. Clinical microbiology reviews 2009, 22(4): 564-581.
[3]	Harris E, Videa E, Perez L, Sandoval E, Tellez Y, Perez ML, Cuadra R, Rocha J, Idiaquez W, Alonso RE et al: Clinical, epidemiologic, and virologic features of dengue in the 1998 epidemic in Nicaragua. The American journal of tropical medicine and hygiene 2000, 63(1-2): 5-11.
[4]	Khor CC, Chau TN, Pang J, Davila S, Long HT, Ong RT, Dunstan SJ, Wills B, Farrar J, Van Tram T et al: Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1. Nat Genet 2011, 43(11): 1139-1141.
[5]	Dang TN, Naka I, Sa-Ngasang A, Anantapreecha S, Chanama S, Wichukchinda N, Sawanpanyalert P, Patarapotikul J, Tsuchiya N, Ohashi J: A replication study confirms the association of GWAS-identified SNPs at MICB and PLCE1in Thai patients with dengue shock syndrome. BMC Medical Genetics 2014, 15(1):1-5.
[6]	Taqi MM, Waseem D, Ismatullah H, Haider SA, Faisal M: In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes. 2016, 16(3):335-345.
[7]	Steinle A, Li P, Morris DL, Groh V, Lanier LL, Strong RK, Spies T: Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics 2001, 53(4):279-287.
[8]	Whitehorn J, Chau TN, Nguyet NM, Kien DT, Quyen NT, Trung DT, Pang J, Wills B, Van Vinh Chau N, Farrar J et al: Genetic variants of MICB and PLCE1 and associations with non-severe dengue. PloS one 2013, 8(3):e59067.
[9]	Chitadze G, Bhat J, Lettau M, Janssen O, Kabelitz D: Generation of soluble NKG2D ligands: proteolytic cleavage, exosome secretion and functional implications. Scandinavian journal of immunology 2013, 78(2):120-129.
[10]	Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV: Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 1992, 30(3): 545-551.
[11]	Cucunawangsih, Lugito NP, Kurniawan A: Immunoglobulin G (IgG) to IgM ratio in secondary adult dengue infection using samples from early days of symptoms onset. BMC infectious diseases 2015, 15:276.
[12]	Khan DM KK, S S, V R M: Evaluation of thrombocytopenia in dengue infection along with seasonal variation in rural melmaruvathur. Journal of clinical and diagnostic research: JCDR 2014, 8(1):39-42.
[13]	Karyanti MR, Uiterwaal CSPM, Kusriastuti R, Hadinegoro SR, Rovers MM, Heesterbeek H, Hoes AW, Bruijning-Verhagen P: The changing incidence of Dengue Haemorrhagic Fever in Indonesia: a 45-year registry-based analysis. BMC Infectious Diseases 2014, 14(1):412.
[14]	Gubler DJ: Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic. Trends Microbiol 2002, 10(2):100-103.
[15]	Guha-Sapir D, Schimmer B: Dengue fever: new paradigms for a changing epidemiology. Emerg Themes Epidemiol 2005, 2(1):1.
[16]	Cummings DA IS, Lessler JT, McDermott A, Prasanthong R, Nisalak A, Jarman RG, Burke DS, Gibbons RV.: The impact of the demographic transition on dengue in Thailand: insights from a statistical analysis and mathematical modeling. PLoS Med 2009, 6(9).
[17]	Thai KT NH, Hoang PL, Tran NT, Phan GT, Le HQ, Tran BQ, Nguyen NV, de Vries PJ: Age-specificity of clinical dengue during primary and secondary infections. PLoS neglected tropical diseases 2011, 5(6).
[18]	Saito M OK, Inoue S, Dimaano EM, Alera MT, Robles AM, Estrella BD Jr, Kumatori A, Moji K, Alonzo MT, Buerano CC, Matias RR, Morita K, Natividad FF, Nagatake T: Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections. Clinical and experimental immunology 2004, 138(2): 299-303.
[19]	WHO: Dengue hemorrhagic fever diagnosis, treatment and control. WHO: Geneva 1997, 2nd edn.
[20]	De Castro RA dCJ, Barez MY, Frias MV, Dixit J, Genereux M.: Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh (o) -D) immune globulin. Am J Trop Med Hyg 2007, 76(4):737-742.
[21]	Mourão MP LM, Macedo VO, Santos JB: Thrombocytopenia in patients with dengue virus infection in the Brazilian Amazon. Platelets 2007, 18(8): 605-612.
[22]	Gonzalez S, Groh V, Spies T: Immunobiology of human NKG2D and its ligands. Curr Top Microbiol Immunol 2006, 298: 121-138.
[23]	Bahram S: MIC genes: from genetics to biology. Advances in immunology 2000, 76: 1-60.
[24]	Groh V, Rhinehart R, Randolph-Habecker J, Topp MS, Riddell SR, Spies T: Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nature immunology 2001, 2(3):255-260.
[25]	Beltran D, Lopez-Verges S: NK Cells during Dengue Disease and Their Recognition of Dengue Virus-Infected cells. Front Immunol 2014, 5:192.
[26]	Petitdemange C, Wauquier N, Rey J, Hervier B, Leroy E, Vieillard V: Control of acute dengue virus infection by natural killer cells. Frontiers in immunology 2014, 5: 209.
[27]	Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Endy TP, Raengsakulrach B, Rothman AL, Ennis FA et al: Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 2000, 181.
[28]	Groh V, Wu J Fau - Yee C, Yee C Fau - Spies T, Spies T: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. (0028-0836 (Print)).
[29]	Salih HR, Rammensee Hg Fau - Steinle A, Steinle A: Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 2002, 169(8)(0022-1767 (Print)):4098-4102.
[30]	WHO: Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. ISBN: 9789241547871 2009, New edition.
[31]	Jayashree K, Manasa GC, Pallavi P, Manjunath GV: Evaluation of platelets as predictive parameters in dengue Fever. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 2011, 27(3): 127-130.
[32]	Croy BA, He H, Esadeg S, Wei Q, McCartney D, Zhang J, Borzychowski A, Ashkar AA, Black GP, Evans SS et al: Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling. Reproduction (Cambridge, England) 2003, 126(2):149-160.
[33]	Lee H, Schlereth SL, Park EY, Emami-Naeini P, Chauhan SK, Dana R: A novel pro-angiogenic function for interferon-gamma-secreting natural killer cells. Investigative ophthalmology & visual science 2014, 55(5):2885-2892.
[34]	Azeredo EL, Zagne SM, Alvarenga AR, Nogueira RM, Kubelka CF, de Oliveira-Pinto LM: Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease. Memorias do Instituto Oswaldo Cruz 2006, 101(4):437-449.
[35]	Mangada MM, Endy TP, Nisalak A, Chunsuttiwat S, Vaughn DW, Libraty DH, Green S, Ennis FA, Rothman AL: Dengue-specific T cell responses in peripheral blood mononuclear cells obtained prior to secondary dengue virus infections in Thai schoolchildren. The Journal of infectious diseases 2002, 185(12):1697-1703.
[36]	Mangada MM, Rothman AL: Altered cytokine responses of dengue-specific CD4+ T cells to heterologous serotypes. Journal of immunology (Baltimore, Md : 1950) 2005, 175(4):2676-2683.