Abstract
Dengue is an arboviral disease caused by dengue virus (DENV) with high prevalence in tropical and sub-tropical regions. Autoimmune syndromes following dengue can be observed in long term follow up. Anti-DENV antibodies are cross-reactive with surface antigens on endothelial cells or platelets and could be involved in the pathogenesis of dengue. However, no studies have analyzed the autoantibody repertoire and its roles in dengue pathogenesis. Hence, we aimed to describe the autoantibody profile in dengue patients with different disease severities. We utilized a protein array with 128 putative autoantigens to screen for IgM and IgG reactivity in plasma obtained from healthy donors (n = 8), asymptomatic individuals infected with DENV (n = 11) and hospitalized dengue patients (n = 21). Even though the patient cohort is small, we show that 80 IgM and 6 IgG autoantibodies were elevated in DENV infected patients compared to age-matched healthy donors. Individuals undergoing a primary DENV infection showed higher amounts of IgG autoantibodies, not IgM autoantibodies, compared to individuals undergoing secondary infection. No differences were observed between asymptomatic and hospitalized dengue patients. Nineteen autoantibodies, which react against several coagulation and complement components, correlated with platelet counts in severe dengue patients. This current study provides a framework to explore a possible role of candidate autoantibodies in dengue immunopathogenesis.
Highlights
Dengue virus (DENV) is a member of the family Flaviviridae, and consists of four distinctDENV serotypes, DENV-1 to DENV-4 [1]
Disease severity ranges from inapparent infection to classic dengue fever (DF) to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)
Even though the patient cohort is small, we show that 80 IgM autoantibodies were elevated in patients infected with DENV compared to age-matched healthy donors, indicating general immune activation after viral infection
Summary
Dengue virus (DENV) is a member of the family Flaviviridae, and consists of four distinct. DENV serotypes, DENV-1 to DENV-4 [1]. An estimated 390 million individuals are infected by DENV each year, of which ~25% are symptomatic [2]. Disease severity ranges from inapparent infection to classic dengue fever (DF) to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). DHF/DSS occurs almost exclusively in patients re-infected with a different dengue serotype where hemorrhage, thrombocytopenia, vascular leakage and shock are the major clinical signs and possible cause of death in those patients [3,4]. No specific treatment is available for dengue. Proposed mechanisms to explain immunopathogenesis include the development of a skewed
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