Indices of anti‐dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase

Posadas-Mondragón, Araceli; Aguilar-Faisal, Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Avila-Trejo, Amanda Marineth; Pacheco-Yépez, Judith del Carmen

doi:10.1111/1348-0421.12536

Cited by 6 publications

(7 citation statements)

References 30 publications

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“…Thein et al 22 showed that serum from subjects with acute DHF or DSS contained higher levels of anti-DENV IgG1 subclass of IgG. Likewise, Posadas-Mondragon et al 23 reported that IgG1 subclass of DENV specific IgG was the predominant subclass during both primary and secondary DENV infections that significantly increased in the patients with secondary DENV infection and DHF. Others 24 have shown that high levels of DENV specific IgA, IgG1, and IgG4 antibodies in serum were markers of high risk for DSS and DHF.…”

Section: Discussionmentioning

confidence: 98%

Zika convalescent macaques display delayed induction of anamnestic cross-neutralizing antibody responses after dengue infection

Valiant

Huang

Vanlandingham

et al. 2018

Emerging Microbes & Infections

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Structural similarities between Zika (ZIKV) and dengue virus (DENV) leads to the induction of cross-reactive responses. We have previously demonstrated that ZIKV exposed macaques significantly enhance DENV viremia. Here we show that this enhancement of DENV infection occurred in the presence of high levels of DENV cross-reactive IgG1 subclass of binding antibodies (bAb) with low DENV neutralizing antibody (nAb) activity (<1:10). The DENV-2 nAb titres after ZIKV infection were, however, higher than those induced in DENV-2 only infected animals suggesting that ZIKV induced low titres of cross-nAb against DENV. Surprisingly, DENV-2 infection of animals previously infected with ZIKV was not accompanied by an anamnestic increase in cross-nAb titres till about 1 week after DENV-2 infection. This delay coincided with enhanced DENV-2 viremia indicating that high levels of cross-bAb in the absence of high nAb contributes to enhancement of DENV infection. Serum collected 8 weeks after DENV-2 infection had high levels of nAb and showed delayed antibody dependent enhancement (ADE) of infection (1:100 dilution) as compared with serum that was collected from ZIKV infected animals prior to DENV-2 infection (1:10 dilution). Examination of serum from macaques that were simultaneously infected with both ZIKV and DENV-2 showed high levels of nAb and delayed ADE responses raising the possibility that the low levels of cross-nAb induced by ZIKV infection could be overcome by co-immunization against ZIKV and DENV infection. Taken together, our results provide additional insights into the nature and kinetics of cross-reactive antibody responses and identify a critical correlate that could potentially prevent enhancement of DENV infection during ZIKV convalescence.

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Section: Discussionmentioning

confidence: 98%

Zika convalescent macaques display delayed induction of anamnestic cross-neutralizing antibody responses after dengue infection

Valiant

Huang

Vanlandingham

et al. 2018

Emerging Microbes & Infections

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“…IgG3 is often one of the earliest subclasses to be elicited against protein antigens upon infection [3,[61][62][63], due to its genetic locus positioning among Ig heavy constant chains (IGHC) in humans [64,65]. Sequentially, IgG3 is the first IGHG gene located within the locus, followed by IgG1 (Gene order as follows: IGHG3, IGHG1, IGHA1, IGHG2, IGHG4, IGHE, and IGHA2 from 5' to 3' [64,65]); thus IgG3 responses are often closely followed by IgG1 responses.…”

Section: Generation Of Igg3 During Various Infection Typesmentioning

confidence: 99%

“…One study found that Chikungunya virus-specific responses are dominated by neutralizing IgG3 Abs, which developed rapidly in patients with high viremia [75]. In contrast, pre-existing IgG in patients, mainly IgG1 and IgG3, against severe Dengue virus (DENV) can form virus-Ab complexes with a different DENV serotype, promoting infection which can lead to complications, such as dengue hemorrhagic fever and dengue shock syndrome [62,76,77]. This cross-serotype activity is referred to as Ab-dependent enhancement (ADE), that is theorized to be due to higher antigen avidity [34], activation of complement [62], and FcγR binding [78,79] compared to same serotype responses.…”

Section: During Early Hiv Infection Functional Ab Responses Decline Drastically With Hivmentioning

confidence: 99%

Role of IgG3 in Infectious Diseases

Damelang

Rogerson

Kent

et al. 2019

Trends in Immunology

157

126

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Immunoglobulin IgG3 comprises only a minor fraction of IgG in human plasma and has remained relatively understudied until recent years. Key physiochemical characteristics of IgG3 include an elongated hinge region, greater molecular flexibility, extensive polymorphisms and additional glycosylation sites not present on other IgG subclasses. These characteristics make IgG3 a uniquely potent immunoglobulin, with the potential for triggering effector functions including complement activation, antibody-mediated phagocytosis or antibody-mediated cellular cytotoxicity. Recent studies underscore the importance of IgG3 effector functions against a range of pathogens and have provided approaches to overcome IgG3-associated limitations, such as allotype-dependent short antibody half-life and excessive pro-inflammatory activation. Understanding the molecular and functional properties of IgG3 may facilitate the development of improved antibody-based immunotherapies and vaccines against infectious diseases. IgG3 allotypic variations can have structural and functional consequences, such as a shorter hinge regions and extended half-life compared to other allotypes [23, 24]. In addition, polymorphisms in the CH3 domain affect the CH3-CH3 interdomain interactions [25], with potential consequences for C1q binding in complement activation [25, 26]. Specific allotypes also contribute to underappreciated difficulties in purifying human IgG3 from serum samples, where only allotypes containing a histidine residue at position 435 can be purified by protein A [27]. Glycosylation of IgG3Glycosylation is a post-translational modification of IgG Abs, which can be regulated by a range of B-cell stimuli, including environmental factors, such as stress or diseases, cytokines and innate immune signaling receptors, such as Toll-like receptors. Hence, exposure to specific pathogens, antigens, or vaccination has the potential to skew Ab glycan profiles [28]. Glycosylation is an inherent mechanism of Ab diversification, on top of V(D)J recombination, somatic hypermutation (SHM) and class switch recombination (CSR), and thereby contributes to the extent of the Ab repertoire of B-cells [29].IgG3 Abs can include up to three potential glycosylation sites. The most well-described glycosylation site is found in all human IgG subclasses, where carbohydrate groups are attached to asparagine 297 in the CH2 domain (Fig. 1c). The glycans at this Nglycosylation site can influence Ab stability [30], binding to Fcγ-receptors (FcγRs)and complement [31], consequently modulating effector functions, such as complement-dependent cytotoxicity (CDC) and Ab-dependent cell cytotoxicity (ADCC) [32][33][34][35][36]. For instance, it has been shown that monoclonal IgG3 Abs expressed

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“…Using published criteria for clinical assessment (Tomashek et al 2018), 27.7% of our patients with PI qualified as severe thrombocytopenia and 38.8% had moderate thrombocytopenia, without significant differences compared with SI (Table 4). We observed a decrease in albumin, along with elevated alanine transaminase (ALT) and aspartate transaminase (AST) in both PI and SI (Table 4) denoting liver inflammation, which has been associated with severity (Oliveira et al 2016, Posadas-Mondragón et al 2017; however, there were no cases of acute hepatitis marked by >10 times ALT increase, unlike in other studies (Souza et al 2004). It has been reported that Ca 2+ levels correlate with disease severity, with hypocalcemia being more prevalent in DHF than in DF (Constantine et al 2014).…”

Section: Discussionmentioning

confidence: 63%

Primary Dengue Infection in Patients Requiring Hospitalization During an Outbreak in a Low Incidence Mexican Region

Cárdenas-Perea

Flores-Mendoza

Pérez-Contreras

et al. 2020

Vector-Borne and Zoonotic Diseases

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Background: Dengue manifestations can range from subclinical to fatal. The study of factors that influence dengue's clinical severity can provide information to potentially limit or predict severe cases. Secondary infection (SI) with a different dengue serotype has been recognized as an important determinant of severity. However, severe dengue (SD) manifestations, including shock, can happen during primary infection (PI) too and the mechanisms involved are less understood. To characterize the severe manifestations associated to PI, we distinguished between primary and secondary dengue cases in hospitalized patients from a region of low and recent dengue incidence in central Mexico. This region can serve as a model for dengue's behavior as it spreads to new areas worldwide. Methods: Dengue-specific immunoglobulin M (IgM) and IgG concentrations were measured in the serum of 78 hospitalized patients with dengue hemorrhagic fever, and their ratios were used to discriminate between PI and SI, as recommended by World Health Organization. Clinical and laboratory manifestations were compared between PI and SI. Results and Conclusions: PI was detected in 23% of hospitalized dengue cases, a proportion similar to that reported in high-incidence regions in Mexico. PI was more frequent in 16-to 40-year-olds, and was absent in patients older than 60 years. Only dengue with warning signs and SD were present in the studied population of hospitalized patients, and case frequency decreased with clinical severity both in PI and SI groups. No significant differences in demographics, laboratory tests, or symptoms were found between PI and SI, which illustrates that cases requiring hospitalization during outbreaks can be severe, even if they are PI. This information can help plan for sanitary contingencies in places where dengue is recently emergent and numerous PI cases are expected. The mechanisms involved in PI clinical severity need to be studied further.Keywords: dengue primary infection, dengue outbreak, dengue IgG and IgM Introduction D engue is a common infection worldwide, with 4.0 billion people (half the world's population) currently at risk (Brady et al. 2012). It is caused by dengue virus (DENV), an arbovirus (arthropod-borne virus) with four serotypes (DENV-1 to 4) that circulate periodically (Wash et al. 2015). Because of its recent and rapid spread all over the world, DENV is considered an emerging pathogen and it is endemic in at least 128 countries (Brady et al.

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Indices of anti‐dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase

Cited by 6 publications

References 30 publications

Zika convalescent macaques display delayed induction of anamnestic cross-neutralizing antibody responses after dengue infection

Zika convalescent macaques display delayed induction of anamnestic cross-neutralizing antibody responses after dengue infection

Role of IgG3 in Infectious Diseases

Primary Dengue Infection in Patients Requiring Hospitalization During an Outbreak in a Low Incidence Mexican Region

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