Kinetics of Dengue Virus-Specific Serum Immunoglobulin Classes and Subclasses Correlate with Clinical Outcome of Infection

Koraka, Penelope; Suharti, Catharina; Setiati, Tatty E.; Mairuhu, A. T. A.; Gorp, E. Van; Hack, C. E.; Juffrie, Mohammad; Sutaryo, J.; Meer, G. M. van der; Groen, Jan; Osterhaus, Albert D. M. E.

doi:10.1128/jcm.39.12.4332-4338.2001

Cited by 107 publications

(94 citation statements)

References 22 publications

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“…and IgG at day 7 p.i (49). The kinetics of isotype production in the A/J mouse model parallels that in human cases, and human Abs against DEN presumably provide protection from reinfection (20,28). In a mouse model for DEN vaccine testing, immunization with DEN vaccine strains resulted in the production of neutralizing Ab titers and protection from lethal DEN challenge (21).…”

mentioning

confidence: 99%

Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

Shresta

Kyle²,

Snider³

et al. 2004

J Virol

290

281

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Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-␣/␤) and IFN-␥ receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-␣/␤ receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-␥ receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4؉ T, or CD8 ؉ T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-␣/␤ is critical for early immune responses to DEN infection, (ii) IFN-␥-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T-and B-cell-dependent immunity in resistance to primary DEN infection in mice.Dengue virus (DEN) is a member of the Flavivirus genus in the Flaviviridae family of single-stranded, positive-polarity, enveloped RNA viruses. DEN causes dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/ DSS), the most common mosquito-borne viral illnesses in humans (3, 5). An estimated 50 million new cases of DF and over 250,000 cases of DHF/DSS occur per year in the subtropical and tropical regions of the world (3). Typically, individuals with primary infection by any one of the four distinct DEN serotypes develop DF, an acute febrile illness with arthralgia, myalgia, and headache (13). In some cases, individuals with primary infection or secondary infection by a different serotype may develop the severe, life-threatening form of DF, called DHF/DSS, with increased vascular permeability, thrombocytopenia, focal or generalized hemorrhages, and shock in cases of DSS (15). A small subset of DHF/DSS patients also exhibit severe central nervous system (CNS) symptoms, such as reduced consciousness, convulsions, and encephalitis (4, 44, 50). Currently, no specific treatment for or vaccines against DEN exist, despite an increase in the geographic distribution of the DEN-transmitting Aedes aegypti and Aedes albopictus mosquitoes, the cocirculation of different DEN serotypes, and the increased frequency of DEN epidemics (14, 45). Thus, dengue is an emerging disease and a major public health concern.At present, the mechanisms of DEN-induced disease and immunity are poorly defined, and the protective versus the pathogenic nature of the immune response to...

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mentioning

confidence: 99%

Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

Shresta

Kyle²,

Snider³

et al. 2004

J Virol

290

281

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“…However, both of these assays are laborious to perform and a period of at least 7 days is required to obtain accurate diagnostic results using them. Recently, several enzyme-linked immunosorbent assays (ELISAs) have become commercially available for the detection of DEN-specific antibodies of different isotypes (6,7).…”

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confidence: 99%

Detection of Immune-Complex-Dissociated Nonstructural-1 Antigen in Patients with Acute Dengue Virus Infections

et al. 2003

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Accurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot blot immunoassay (DBI) was compared to a commercially available DEN antigen detection kit (denKEY Blue kit; Globio Co., Beverly, Mass.) and a reverse transcription-PCR (RT-PCR) kit. Serial serum or plasma samples (n ‫؍‬ 181) obtained from 55 acute DEN-infected patients were used. In samples obtained from 32 of these 55 DEN-infected patients, viral RNA could be detected by RT-PCR. DEN antigen was detected in only 10 of these 55 patient samples by using the denKEY kit. When these samples were treated with acid to release the immune-complex-associated NS-1 antigen for detection by DBI, 43 of these 55 patients were found to be positive for DEN NS-1 antigen. In nondissociated samples, 22 of these patients were found to be positive by the DBI. In the presence of DEN-specific immunoglobulin M antibodies, both viral RNA and DEN (NS-1) antigen could be detected. The number of positive samples identified by RT-PCR and DBI from these patients with primary DEN infections varied between 28 and 78%. In secondary DEN infections, the number of samples that tested positive by the DBI after immune-complex dissociation (DIS-DBI) was 25% higher than the number of samples that tested positive by RT-PCR and was 35% higher than that determined by nondissociated antigen (NDIS-DBI) detection. We conclude that the denKEY kit has limited diagnostic value for acute DEN infections compared to the RT-PCR and the NDIS-DBI and DIS-DBI methods. We clearly demonstrate that in secondary DEN infections the dissociation of NS-1 immune complexes is essential for early diagnosis of DEN infections.Dengue virus (DEN) is one of the most widespread mosquito-borne human pathogens worldwide, accounting for more than 50 million infections per year (10). Mosquitoes of the Aedes species are responsible for transmitting the four serotypes of DEN (DEN1 to DEN4) to humans. Infection with DEN may be asymptomatic or may cause a variety of symptoms ranging from mild dengue fever (DF) to the more severe form of dengue hemorrhagic fever (DHF) with or without shock (dengue shock syndrome [DSS]) (17). In areas where DEN is endemic, DHF has become an increasingly important cause of pediatric morbidity and mortality since it was first described half a century ago (17). Accurate diagnosis of DEN infections is therefore essential.The diagnostic methods of choice for the identification of DEN infections have been the plaque reduction neutralization assay and/or virus isolation from patient serum samples by using mosquito cell lines (17, 18). However, both of these assays are laborious to perform and a period of at least 7 days is required to obtain accurate diagnostic results using them. Recently, several enzyme-linked immunosorbent assays (ELISAs) have become commercially available for the...

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“…20 It has been reported that in individuals with FcγRIIa-R/R131 genotypes as the predominant polymorphic variants, IgG1 and IgG3 bind efficiently. 8,21 In addition, the signal generated after interaction between FcγRIIa and the virus-antibody (DENV/IgG1/3) complex may be associated with an efficient phagolysosome formation 22 and the elimination of the immune complex and control of viral dissemination.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic Dengue Infection in a Cuban Population Confirms the Protective Role of the RR Variant of the FcγRIIa Polymorphism

Garcı́a¹,

Sierra²,

Pérez³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. The role of human Fcγ receptors (FcγR) has been recognized considerably over the last years. These receptors vary in their affinity for IgG subclasses and the intracellular signals elicited by them. Allelic variants of FcγR genes may influence the biological phagocyte activity, accounting for an inherited pre-disposition to disease. The specific FcγRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated to a reduced risk for developing dengue hemorrhagic fever (DHF). Here, we investigated the role of this polymorphism in a very well-characterized group of Cuban individuals with antecedents of DHF, dengue fever (DF), or subclinical dengue infection. The HH131 genotype was significantly associated with dengue disease, either DF (* P = 0.016; odds ratio = 4.425; 95% confidence interval = 1.10-20.52) or DHF ( P = 0.00018; odds ratio = 10.56; 95% confidence interval = 2.33-54.64) with respect to the subclinical infection.

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Kinetics of Dengue Virus-Specific Serum Immunoglobulin Classes and Subclasses Correlate with Clinical Outcome of Infection

Cited by 107 publications

References 22 publications

Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

Detection of Immune-Complex-Dissociated Nonstructural-1 Antigen in Patients with Acute Dengue Virus Infections

Asymptomatic Dengue Infection in a Cuban Population Confirms the Protective Role of the RR Variant of the FcγRIIa Polymorphism

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