Association of human leukocyte antigen DQ1 and dengue fever in a white Southern Brazilian population

Polizel, José Roberto; Bueno, Danilo; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria; Borelli, Sueli Donizete; Tsuneto, Luiza Tamie; Dalálio, M. M. O.; Coimbra, Maria Teresa M; Moliterno, Ricardo Alberto

doi:10.1590/s0074-02762004000600003

Cited by 35 publications

(33 citation statements)

References 18 publications

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“…While either the I-E or the I-A molecule has been shown to suppress the generation of autoantibodies to different antigens (4,16), these B10.BR mice still generated highly cross-reactive antibody ELISA titers to the human platelets and fibrinogen after live D-2V infections (Figure 3) or immunizations with the purified D-2V NS1 protein (6). The HLA-DR4 molecule, positively selected in the Latin American populations, was associated with DHF resistance (20), while the HLA-DQ1 molecule provided DHF resistance in Brazilian populations (24). During a large DHF epidemic in Cuba, some diseases known to be associated with particular HLA class II haplotypes, such as bronchial asthma, were identified as DHF risk factors (15).…”

Section: Discussionmentioning

confidence: 96%

“…Antibody responses to the purified D-2V NS1 protein were influenced by H-2 class II molecules in mice, but all of these PAbs cross-reacted with human fibrinogen, endothelial cells, and platelets, as was observed with MAb 1G5.4-A1-C3 (6), and human class II molecules (HLAs) were shown to affect resistance or susceptibility to DHF (20,24). In this study, (i) the individual reactions of the four MAbs which defined the LX1 epitope against the NS1 proteins of each dengue virus serotype and a panel of other flaviviruses as described previously (6, 10) were compared; (ii) mouse H-2 class II molecules were tested for their abilities to influence PAb responses to the LX1 and ELK/KLE-type epitopes on the NS1 protein after repeated D-2V infections; (iii) the cross-reactions of the PAbs generated in step ii with human fibrinogen and platelets were tested; (iv) a peptide containing the LX1 and ELK-type epitopes was designed, and its potential as an inexpensive diagnostic reagent was tested; and (v) the immunodominance of the LX1 and ELK-type epitopes was tested by using PAbs generated in mice, rabbits, and human patients with DF and DSS.…”

mentioning

confidence: 89%

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Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design

Falconar

2007

Clin Vaccine Immunol

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Antibodies generated to the purified dengue type 2 virus (D-2V) nonstructural-1 (NS1) protein in mice and rabbits were compared with those generated to this protein in congeneic (H-2 class II) mouse strains and humans after D-2V infections. Unlike the profiles observed with the rabbits, similar antibody reaction profiles were generated by mice and humans with severe D-2V disease (dengue hemorrhagic fever [DHF]/dengue shock syndrome [DSS]). Many of these epitopes contained the core acidic-hydrophobic-basic (tri-amino-acid; ELKtype) motifs present in the positive or negative orientations. Antibody responses generated to these ELK/KLEtype motifs and the epitope LX1 on this protein were influenced by class II molecules in mice during D-2V infections; but these antibodies cross-reacted with human fibrinogen and platelets, as implicated in DHF/DSS pathogenesis. The core LX1 epitope ( 113 YSWKTWG 119 ), identified by the dengue virus complex-specific monoclonal antibody (MAb) 3D1.4, was prepared so that it contained natural I-A d -binding and ELK-type motifs. This AFLX1 peptide, which appropriately displayed the ELK-type and LX1 epitopes in solid-phase immunoassays, generated a similar, but lower, immunodominant anti-ELK-motif antibody reaction in I-A dpositive mice, as generated in mice and humans during D-2V infections. These antibody responses were much stronger in the high-responding mouse strains and each of the DHF/DSS patients tested and may therefore account for the association of DHF/DSS resistance or susceptibility with particular class II molecules and autoantibodies, antibody-stimulating cytokines (e.g., interleukin-6), and complement product C3a being implicated in DHF/DSS pathogenesis. These results are likely to be important for the design of a safe vaccine against this viral disease and showed the AFLX1 peptide and MAb 3D1.4 to be valuable diagnostic reagents.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 89%

Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design

Falconar

2007

Clin Vaccine Immunol

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“…Human genetic background factors in DHF have not been extensively studied. Few studies suggest HLA association with dengue disease severity (45,52). In this study we noticed that several peptides specific to HLA-A*02 and HLA-A*24 evoked very high IFN-␥ responses.…”

Section: Vol 14 2007 T-cell Responses To Ns Regions Of Dengue Virusmentioning

confidence: 99%

Cross-Reactive T-Cell Responses to the Nonstructural Regions of Dengue Viruses among Dengue Fever and Dengue Hemorrhagic Fever Patients in Malaysia

Appanna

Huat

See

et al. 2007

Clin Vaccine Immunol

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Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3 422-431 were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3 422-431 and NS5 563-571 in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3 422-431 . A large number of patients' T cells also responded to the NS2B 97-106 region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.

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“…About 2.5% of those affected die. 152 Several studies [155][156][157][158][159][160][161][162][163] have been conducted about the role of HLA alleles or non HLA alleles in determining resistance, susceptibility or the severity of dengue viral infection, yet only superficial efforts have been made. Thus, a need for detailed genetic studies in different ethnic groups in different countries on a large number of patients is required.…”

Section: Hla and Dengue Virus Infectionmentioning

confidence: 99%

Major histocompatibility complex and its importance towards controlling infection

Longjam

Das

2017

Asian J Med Sci

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It is well documented that infectious pathogen burden and infected cell mass determine the clinical severity of infectious diseases, however, the ability of the host to recognize and process antigens to produce antibodies or the cellular immune response during infection could be under genetic control. The Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) system is the most intensively studied of all genetic systems because of its influence to many important traits, including resistance to infectious diseases, autoimmunity and immunological self or nonself compatibility. This is understandable in the light of the evolutionary pressure so that we are equipped to face the multitude of infectious challenges. Infectious diseases are a major selective pressure;and genes involved in the immune response are the most numerous and diverse in the human genome; reflecting the evolutionary advantages of a diverse immunological response to a wide range of infectious pathogens.Asian Journal of Medical Sciences Vol.8(2) 2017 1-13

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Association of human leukocyte antigen DQ1 and dengue fever in a white Southern Brazilian population

Abstract: Dengue is an infectious disease of viral etiology transmitted by the mosquitoes

Cited by 35 publications

References 18 publications

Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design

Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design

Cross-Reactive T-Cell Responses to the Nonstructural Regions of Dengue Viruses among Dengue Fever and Dengue Hemorrhagic Fever Patients in Malaysia

Major histocompatibility complex and its importance towards controlling infection

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