Antibodies in Sera of Dengue Patients with Plasma Leakage Cross-Reacting with DENV Protein and Endothelial Protein

Dewi Wulandari, Alida Roswita Harahap, Suhendro Suhendro, R. Tedjo Sasmono, Aryati Aryati, Herdiman Theodorus Pohan, Iris Rengganis, Saptawati Bardosono

Abstract


BACKGROUND: Dengue infection remains a major public health problem in Indonesia. Severe dengue associated with plasma leakage require hospitalization and potentially life threatening. However, the mechanism remains unclear, and the occurrence is unpredictable. The role of anti-endothelial antibody is predicted play an important role in the pathogenesis of plasma leakage, as severe dengue is more prevalent in secondary infection or post vaccinated individuals.

METHODS: Serum samples from 127 single Dengue Virus (DENV) serotype infected subjects were obtained in day 2 of fever onset. Subjects were divided into plasma leakage and non-plasma leakage based on World Health Organization (WHO) criteria. Anti-endothelial antibody in patient sera were detected using western blot of Human Umbilical Vein Endothelial Cells (HUVEC). To confirm cross-reactivity, the sera was preabsorb with mix-DENV lysate.

RESULTS: Three prominent bands were identified on western blot strips that inhibited by pre-absorption with DENV lysate. Plasma leakage patient expressed significantly more antibodies, with 51.7% of plasma leakage patients expressed at least two bands out of those three, compared to 18.5% of non-plasma leakage.

CONCLUSION: Antibodies found in sera of dengue patients with plasma leakage cross-reacted with DENV proteins and endothelial proteins 37 kDa, 75 kDa, 120 kDa, and therefore may be involved in the pathogenesis of plasma leakage. Proteomic identification of those protein targets is needed and may be useful for vaccine studies and further development of predictor marker for plasma leakage in dengue.

KEYWORDS: severe dengue, plasma leakage, cross-reactive, anti-endothelial antibody.


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References


Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. Global distribution and burden of dengue. Nature. 2013; 496(7446): 504-7, CrossRef.

Murray NE, Quam MB, Wilder-Smith A. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol. 2013; 5: 299-309, CrossRef.

Wahyono TYM, Nealon J, Beucher S, Prayitno A, Moureau A, Nawawi S, et al. Indonesian dengue burden estimates: review of evidence by an expert panel. Epidemiol Infect. 2017; 145(11): 2324-9, CrossRef.

World Health Organization (WHO) [Internet]. Dengue and Severe Dengue [updated 2021 May 19; cited Dec 1, 2021]. Available at: https://www.who.int/.

Sun Y, Jin C, Zhan F, Wang X, Liang M, Zhang Q, et al. Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis. 2012; 206(7): 1085-94, CrossRef.

Basu A, Chaturvedi UC. Vascular endothelium: the battlefield of dengue viruses. FEMS Immunol Med Microbiol. 2008; 53(3): 287-99, CrossRef.

Srikiatkhachorn A. Plasma leakage in dengue haemorrhagic fever. Thromb Haemost. 2009; 102(6): 1042-9, CrossRef.

Intansari US, Salim H, Sukorini U, Juffrie M. High expression of FcγII (CD32) receptor on monocytes in dengue infected patients. Indones Biomed J. 2018; 10(3): 256-62, CrossRef.

Olagnier D, Amatore D, Castiello L, Ferrari M, Palermo E, Diamond MS, et al. Dengue virus immunopathogenesis: lessons applicable to the emergence of zika virus. J Mol Biol. 2016; 428(17): 3429-48, CrossRef.

Rachman A, Harahap AR, Widhyasih RM. The role of anti-dengue virus NS-1 and anti-protein disulfide isomerase antibodies on platelet aggregation in secondary dengue infection. Acta Medica Indonesiana. 2013; 45(1): 43-8, article.

Khurram M, Qayyum W, Ul Hassan SJ, Mumtaz S, Bushra HT, Umar M. Dengue hemorrhagic fever: Comparison of patients with primary and secondary infections. J Infect Public Health. 2014; 7(6): 489-95, CrossRef.

Suwarto S, Nainggolan L, Sinto R, Effendi B, Ibrahim E, Suryamin M, et al. Dengue score: a proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection. BMC Infect Dis. 2016; 16: 322, CrossRef.

Cardosa MJ, Wang SM, Sum MSH, Tio PH. Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses. BMC Microbiol. 2002; 2: 9, CrossRef.

Baudin B, Bruneel A, Bosselut N, Vaubourdolle M. A protocol for isolation and culture of human umbilical vein endothelial cells. Nat Protoc. 2007; 2(3): 481-5, CrossRef.

Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000; 181(1): 2-9, CrossRef.

Suwarto S, Sasmono RT, Sinto R, Ibrahim E, Suryamin M. Association of endothelial glycocalyx and tight and adherens junctions with severity of plasma leakage in dengue infection. J Infect Dis. 2017; 215: 992-9, CrossRef.

Fujimoto DE, Koifman S. Clinical and laboratory characteristics of patiens with dengue hemorrhagic fever manifestations and their transfusion provile. Rev Bras Hematol E Hemoter. 2014; 36(2): 115-20, CrossRef.

Karoli R, Fatima J, Siddiqi Z, Kazmi KI, Sultania AR. Clinical profile of dengue infection at a teaching hospital in North India. J Infect Dev Ctries. 2012; 6: 551-4, CrossRef.

Potts JA, Thomas SJ, Srikiatkhachorn A, Supradish P, Li W, Nisalak A, et al. Classification of dengue illness based on readily available laboratory data. Am J Trop Med Hyg. 2010; 83(4): 781-8, CrossRef.

Suwarto S, Hidayat MJ, Widjaya B. Dengue score as a diagnostic predictor for pleural effusion and/or ascites: external validation and clinical application. BMC Infect Dis. 2018; 18: 90, CrossRef.

Muller DA, Young PR. The flavivirus NS1 protein: Molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker. Antivir Res.2013; 98(2): 192-208, CrossRef.

Amorim JH, Alves RP, Boscardin SB, Ferreira LC. The dengue virus non-structural 1 protein: risks and benefits. Virus Res. 2014; 181: 53-60, CrossRef.

Chuang YC, Wang SY, Lin YS, Chen HR, Yeh TM. Re-evaluation of the pathogenic roles of nonstructural protein 1 and its antibodies during dengue infection. J Biomed Sci. 2013; 20: 42, CrossRef.

Lin CF, Lei HY, Shiau AL, Liu CC, Liu HS, Yeh TM, et al. Antibody from dengue patient sera cross-react with endothelial cells and induce damage. J Med Virol. 2003; 69(1): 82-90, CrossRef.

Liu IJ, Chiu CY, Chen YC, Wu HC. Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus. J Biol Chem. 2011; 286(11): 9726-36, CrossRef.

Wan SW, Lin CF, Yeh TM, Liu CC, Liu HS, Wang S, et al. Autoimmunity in dengue pathogenesis. J Formos Med Assoc. 2013; 112(1): 3-11, CrossRef.




DOI: https://doi.org/10.18585/inabj.v14i1.1771

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