Polymorphisms of the TAP 1 and 2 gene may influence clinical outcome of primary dengue viral infection

Antigen peptides are actively transported across the endoplasmic reticulum by the transporters associated with antigen presentation (TAP). TAP genes polymorphism could influence the selection process that determines which antigen peptides play a role in the pathogenesis of dengue infection. The aim of this study was to investigate the association of TAP genes polymorphism in diverse pathogenesis of dengue infection. This study included 197 dengue-infected patients who were further categorized into 64, 23 and 11 primary dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) cases, respectively and 26, 52, and 21 secondary DF, DHF and DSS cases, respectively as per WHO grading system. TAP1 and 2 gene polymorphisms were performed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Analysis of TAP1 gene polymorphism demonstrated decreased frequency of Ile/Ile genotype at TAP1(333) in primary DHF cases (39.1%) when compared with primary DF (64.1%, P < 0.034, OR = 0.611). The genotype frequency of Val/Val at TAP2(379) locus was significantly decreased among primary DHF (43.5%) in comparison to primary DF (71.9%, P = 0.015, OR = 0.605). Significant low proportion of primary DSS were found to have TAP1(637) Asp/Asp genotypes (54.5%) when compared with primary DF (70.3%, P = 0.043). Asp/Asp genotype at TAP1(637) was found to reduce the risk by 0.643 times for primary DSS. There was no significant difference in the genotypes studied between primary and secondary infection and also within secondary dengue infection in all three clinical groups. This report on TAP gene polymorphisms in dengue suggested that among the primary-infected individuals, homozygous patterns for Ile at TAP1(333) Val at TAP2(379) loci and Asp at TAP1(637) were found to be a protective factor against development of DHF and DSS, respectively.     

Immunopathogenesis of dengue hemorrhagic fever and shock syndrome: role of TAP and HPA gene polymorphism

Clinical outcomes of dengue infection such as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) could be attributed to host genetic factors. The transporters associated with antigen processing (TAP) genes are polymorphic genes located in the human leukocyte antigen (HLA) class II region and are essentially involved in class I antigen presentation. Therefore, these genes might grant susceptibility to severe dengue infection. Hence, the aim of the study was to type the TAP1 gene (using amplification refraction mutation system [ARMS] polymerase chain reaction [PCR]) and HPA1 and HPA2 gene polymorphism (by PCR–sequence specific primers) in different clinical spectrums of dengue infection. The study included 100 controls and 91 DF, 75 DHF, and 32 DSS patients. The results revealed that the frequencies of valine at TAP1 333 and HPA 1b at HPA1 were increased among DHF and DSS, respectively, in comparison to controls (p <0.05). The frequency of genotype TAP1 333 ILE/VAL (61.3%) was significantly higher in DHF compared with control (37%, p = 0.005) or DF (38.9%, p = 0.007) patients. A significantly greater proportion of DHF patients demonstrated HPA1a/1a and HPA 2a/2b genotypes than DF patients. DSS patients were more likely to be heterozygous at HPA1 than DHF (OR = 4.75, p = 0.003). A positive correlation existed between TAP1 333 and HPA1 in DHF (p = 0.017, r = 0.229). This first report on TAP and HPA gene polymorphism in dengue suggested that the heterozygous pattern at the TAP1 333 locus and HPA1a/1a and HPA2a/2b genotypes confer susceptibility to DHF and the HPA1a/1b genotype was determined to be a genetic risk factor for DSS.     

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Killer cell immunoglobulin‐like receptors (KIRs) regulate the activation of natural killer cells (NKs). Qualitative and quantitative differences in the type and the number of KIRs expressed on NK cells affect its activation which would influence the outcome of the disease. In this study, 114 hospitalized cases of dengue [82 dengue fever (DF) and 32 dengue haemorrhagic fever (DHF) cases] and 104 healthy controls (HC) without no known history of hospitalization for dengue‐like illness were investigated for their KIR gene profile to find out the association of KIR genes with dengue disease severity. KIR gene profile was investigated using duplex sequence‐specific priming polymerase chain reaction‐based typing system. The results revealed a higher frequency of KIR3DL1 gene [P = 0.0225; odds ratio (OR) 4.1 95% confidence interval (CI) 1.1–14.8] and lower frequency of KIR3DS1/3DS1 genotype [P = 0.0225; OR 0.24 95% CI (0.068–0.88)] in DF cases compared to HC. Immunoglobulin‐like receptor gene frequencies were not different between DHF and DF or HC. The results suggest that KIR3DL1/KIR3DS1 locus might be associated with the risk of developing DF.     

Polymorphisms of the TAP1 and TAP2 genes in human alveolar echinococcosis

We postulated that TAP genes may influence the susceptibility of some individuals to Echinococcus multilocularis infection. Six coding region variants (codons 333 and 637 in TAP1, and 379, 565, 651 and 665 in TAP2) were typed in 94 patients and 100 controls. Thr/Thr homozygosity at TAP2/665 was more prevalent in patients than in controls [64% vs. 45%, respectively; odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.1; 2.7)] and Thr/Ala heterozygozity was less prevalent (32% vs. 50%, respectively) (P = 0.014). Of the 38 patients with progressive lesions, 76% were Thr/Thr, as compared with 55% of patients without progressive lesions and 45% of controls (P = 0.058 and 0.02, respectively), independent of HLA status. To determine whether this association is functionally relevant, functional analyses and/or confirmation in distinct populations of patients with alveolar echinococcosis would be required.     

TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France

The ‘transporter associated with antigen processing’ (TAP) gene products are involved in the processing of endogenous peptides that bind to class I molecules. Polymorphism within these genes could alter the level of the immune response, a phenomenon relevant to the development of autoimmune diseases. In this study, we examined the polymorphism of TAP1 and TAP2 genes in patients with rheumatoid arthritis (RA). TAP1 and TAP2 typing was performed for 138 Caucasian RA patients and 100 healthy controls, all originating from eastern France. TAP1 polymorphic residues at positions 333 and 637 and amino acid variants 379, 565, 651 and 665 in the TAP2 gene were found using amplification refractory mutation system–polymerase chain reaction (ARMS‐PCR). This method enabled us to determine four TAP1 alleles (TAP1A to TAP1D) and eight TAP2 alleles (TAP2A to TAP2H). All patients and controls had been HLA‐DRB1* genotyped. The polymorphic residues TAP1³³³ and TAP1⁶³⁷ did not show any difference in their distribution between patients and controls. Similar findings were obtained for TAP2³⁷⁹ and TAP2⁶⁶⁵. However, we found an increased frequency of Thr homozygosity and heterozygosity at position 565 in the TAP2 gene in RA patients (RA vs. controls: 25.3 vs. 14%; P = 0.032; OR = 2.09; CI = 1.01–4.38). Similarly, the prevalence of subjects who were homozygote and heterozygote for Cys⁶⁵¹ was increased in the RA group (RA vs. controls: 36.8 vs. 11%; P = 0.02). The dimorphic site TAP2⁵⁶⁵ defines TAP2D and TAP2E alleles, while the site at position 651 characterizes TAP2F. Thus, we found that TAP2D and TAP2E alleles were more prevalent in RA, but not significantly so (RA vs. controls: TAP2D: 10 vs. 3.6%; P = 0.24; TAP2E: 3.6 vs. 0%; P = 0.19). Similarly, the frequency of TAP2F was higher in RA patients (24.5%) than in controls (11.3%), but this was not significant after correction (P = 0.029; P_corr = 0.17). Finally, we found no linkage disequilibrium between DRB1* RA‐associated alleles and amino acid substitution Thr⁵⁶⁵ or TAP2D and TAP2E alleles, whereas Cys⁶⁵¹ (and TAP2F) was not independent of DRB1*04, a strongly RA‐associated allele. Finally, Thr at position 565 in the TAP2 gene was associated with manifestations of disease severity in only a few patients. Examination of TAP1 and TAP2 gene polymorphisms in RA patients revealed an association between a particular amino acid residue, namely Thr⁵⁶⁵ in the TAP2 gene, and RA. This association was found to be weak and did not seem to be a predictor for the severity of the disease.     

High Producing Tumor Necrosis Factor Alpha Gene Alleles in Protection against Severe Manifestations of Dengue

Dengue virus (DENV) infection usually presents with mild self-limiting dengue fever (DF). Few however, would present with the more severe form of the disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In the present study, the association between IL-12B, IL-10 and TNF-α gene polymorphisms and dengue severity was investigated. Methods: A case-control study was performed on a total of 120 unrelated controls, 86 DF patients and 196 DHF/DSS patients. The polymorphisms in IL-12B, IL-10 and TNF-α genes were genotyped using PCR-RFLP and PCR-sequencing methods. Results: A protective association of TNF-α -308A allele and -308GA genotype against DHF/DSS was observed, while TNF-α -238A allele and -238GA genotype were associated with DHF/DSS. A combination of TNF-α -308GA+AA genotype and IL-10 non-GCC haplotypes, IL-12B pro homozygotes (pro1/pro1, pro2/pro2) and IL-12B 3''UTR AC were significantly correlated with protective effects against DHF/DSS. An association between the cytokine gene polymorphisms and protection against the clinical features of severe dengue including thrombocytopenia and increased liver enzymes was observed in this study. Conclusion: The overall findings of the study support the correlation of high-producer TNF-α genotypes combined with low-producer IL-10 haplotypes and IL-12B genotypes in reduced risk of DHF/DSS.     

Association of vitamin D receptor gene polymorphisms with clinical outcomes of dengue virus infection

Vitamin D is known to affect pathogenesis of dengue through modulation of immune responses. Vitamin D exerts its effects through vitamin D receptor (VDR). The functioning of VDR is affected by the gene polymorphisms in the coding (rs2228570) and 3′untranslated region (UTR) (rs1544410, rs7975232 and rs731236). In the present study, VDR gene polymorphisms were investigated in 112 dengue infected patients (83 dengue fever (DF) and 29 dengue hemorrhagic fever cases (DHF)) and 105 apparently healthy controls (HCs) using polymerase chain reaction based restriction fragment length polymorphisms methods. HCs had no documented evidence of symptomatic dengue. Results revealed significantly lower frequency of ‘C’ allele of rs7975232 in all dengue patients (DEN) as compared to HCs [(P corrected (Pc) = 0.014, Odds ratio (OR) 0.51]. The frequency of C/C genotype of rs7975232 was significantly lower in DEN and DF cases compared to HCs (DEN vs. HCs: Pc = 0.0184, OR 0.24; DF cases vs. HCs: Pc = 0.028, OR 0.21). The frequency of T allele of rs2228570 in a dominant mode was significantly higher in DHF cases as compared to DF cases (P = 0.034 OR 2.58). A significantly lower frequency of the haplotype G-C-T (Pc = 0.0135) and higher frequency of the haplotype G-A-T (Pc = 0.000085) was observed in DEN and DF cases as compared to HCs. The results suggest that the 3′UTR haplotypes of VDR gene are differentially associated with risk of symptomatic dengue requiring hospitalization. The ‘T’ allele of rs2228570 polymorphism in a dominant mode of inheritance is associated with DHF.     

Kinetics of dengue virus-specific serum immunoglobulin classes and subclasses correlate with clinical outcome of infection.

The kinetics of dengue virus (DEN)-specific serum immunoglobulin classes (immunoglobulin M [IgM] and IgA) and subclasses (IgG1 to IgG4) were studied in patients suffering from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Serum samples from non-DEN febrile patients were included as controls. IgM, IgG1, and IgG3 serum antibodies were the predominant immunoglobulins throughout the course of illness in all three patient groups. In contrast, IgA antibodies were significantly higher in the acute phase in DSS patients compared to those in DF patients (P < 0.05). The levels of IgG1 differed significantly between patients with DF and those with DHF and DSS (P < 0.05). A significant difference was also found in IgG3 levels between DF patients and DHF patients (P < 0.05) but not between DF patients and DSS patients. Finally, levels of IgG4 antibodies differed significantly between DF patients and DSS patients (P < 0.05). Collectively, these data show that increased levels of DEN-specific IgA, IgG1, and IgG4 serum antibodies are risk markers for the development of DHF and DSS and that their measurement may provide valuable guidance for early therapeutic intervention.     

Diabetic patients suffering dengue are at risk for development of dengue shock syndrome/severe dengue: Emphasizing the impacts of co-existing comorbidity(ies) and glycemic control on dengue severity

Background/PurposeThe impact of type 2 diabetes mellitus (DM2) on clinical severity of dengue has not been fully understood. We aimed to assess risk factors for dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) and severe dengue (SD) (defined based on the World Health Organization 1997 and 2009 dengue classifications), and additionally identify, among DM2 patients, who are at risk for developing DHF/DSS and severe dengue.MethodsA retrospective analysis of dengue patients diagnosed between 2002 and 2010. Risk factors for development of DHF/DSS/SD were identified using multivariate analysis. To elucidate the impacts of coexisting comorbidity(ies) (i.e., hypertension, chronic kidney disease, old stroke, and/or ischemic heart disease) and glycemic control on clinical outcomes of dengue in DM2 patients, the overall DM2 patients and stratified DM2 patients (HbA1c < 7% vs. HbA1c ≧ 7%), with or without comorbidity(ies), were separately compared to controls (patients without any morbidity).ResultsOf 767 (146 DM2 and 621 controls) included patients, 1.4% suffered DSS and 3.3% SD. While DM2 was an independent risk factor for DSS (adjusted odds ratio [AOR] = 7.473; 95% confidence interval [CI] = 2.221–25.146) and SD (AOR = 6.207; 95% CI = 2.464–15.636), only DM2 patients with additional comorbidity(ies) and suboptimal glycemic control (HbA1c ≧ 7%) had significantly higher incidences of non-shock DHF (60.8% vs. 29%), DSS (8.7% vs. 0.8%) and SD (34.8% vs. 1.1%).ConclusionsThese data could help narrow down the number of targets in the triage for risky DM2 dengue patients to those with suboptimal glycemic control and co-existing comorbidity(ies).     

Phenotypic and genotypic characterization of dengue virus isolates differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome

Dengue viruses (DENV) cause 50-100 million cases of acute febrile disease every year, including 500,000 reported cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Viral factors have been proposed to influence the severity of the disease, but markers of virulence have never been identified on DENV. Three DENV serotype-1 isolates from the 2007 epidemic in Cambodia that are derived from patients experiencing the various clinical forms of dengue were characterized both phenotypically and genetically. Phenotypic characteristics in vitro, based on replication kinetics in different cell lines and apoptosis response, grouped isolates from DF and DHF patients together, whereas the virus isolate from a DSS patient showed unique features: a lower level of replication in mammalian cells and extensive apoptosis in mosquito cells. Genomic comparison of viruses revealed six unique amino acid residues in the membrane, envelope, and in non-structural genes in the virus isolated from the DSS patient.     

Determination of tumor necrosis factor-alpha levels in dengue virus infected patients by sensitive biotin-streptavidin enzyme-linked immunosorbent assay

A modified sandwich enzyme-linked immunosorbent assay using biotin-streptavidin system (BS-ELISA) was developed to determine levels of tumor necrosis factor-alpha (TNF-alpha) in serum samples of children infected with dengue virus (n=99) and healthy controls (n=41). The minimum detectable concentration of TNF-alpha by the BS-ELISA was 3.3 pg/ml. The mean TNF-alpha level was highest in those patients with dengue shock syndrome (DSS) or dengue hemorrhagic fever (DHF) grade III (37.44+/-42.0 pg/ml). Lower levels were found in DHF grade I (28.44+/-42.7 pg/ml), DHF grade II (24. 21+/-25.4 pg/ml) and dengue fever (DF) (14.10+/-24.0 pg/ml). TNF-alpha in the sera of DF and DHF patients could be detected on days 2-6 after the onset of fever, the high level occurring on day 5. TNF-alpha was detected in 41.4% (24.01+/-35.2 pg/ml) of dengue virus infected patients and 7.3% (4.2+/-15.6 pg/ml) of control subjects. The sera of patients contained significantly higher levels of TNF-alpha than the sera of controls, P-value<0.001. DHF patients had significantly higher levels of TNF-alpha than DF patients (P-value=0.020) but no difference in the TNF-alpha levels from sera of DHF grades I-III patients was observed (P-value=0.295). The results indicate that the BS-ELISA is a very sensitive method for determining TNF-alpha in serum samples of DF and DHF patients. The TNF-alpha levels might be associated with dengue virus infection and related to disease severity of DHF.     

Antibodies from patients with dengue viral infection mediate cellular cytotoxicity.

Acute and late convalescent sera (collected at day 5 of disease onset and 1 year later) from dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) laboratory confirmed cases, were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) activity using dengue 1 (DENV-1) or dengue 2 (DENV-2) infected cells as target. All patients experienced their first dengue virus (DENV) infection 20 years before. ADCC activity was detected in acute sera from DHF/DSS but not in sera from DF patients. However, 1 year after illness, ADCC activity was observed in all cases. This preliminary report represents one of the few studies of ADCC in dengue patients and suggests that ADCC could be implicated in dengue pathogenesis.     

Elevated serum PAR-1 levels as an emerging biomarker of inflammation to predict the dengue infection severity

The present study was designed to check the serum levels of protease-activated receptor (PAR-1) in patients during different phases of dengue severity. Moreover, a correlation between serum PAR-1 levels and hematological parameters, inflammatory cytokine levels, and liver functional changes was also determined. Based on the World Health Organization criteria, the study population was divided into: nonsevere dengue fever (DF; n = 30), severe dengue hemorrhagic fever (DHF; n = 19), and severe dengue shock syndrome (DSS; n = 11). The platelet count (PLT) and hematocrit (HCT) were analyzed using an automated hematology analyzer and liver function enzymes aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphate (ALP), bilirubin were checked by auto-analyzer using diagnostic kits. Moreover, the levels of inflammatory mediators C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and PAR-1 were determined using respective ELISA kits. The HCT levels were elevated and platelet count decreased significantly during dengue complications (DHF and DSS) compared to the DF patients, while the levels of liver functional biomarkers AST, ALT, ALP, and bilirubin remained elevated in DHF and DSS groups than in the corresponding DF group. Similarly, the inflammatory cytokine levels of CRP, TNF-α, IL-6, and IL-17 in DHF and DSS subjects were markedly increased when observed against DF subjects. Notably, the PAR-1 levels were significantly elevated in DHF and DSS groups than in the DF group and positively correlated with changes in HCT levels, inflammatory biomarkers, and liver enzymes. Our findings conclude that PAR-1 levels persistently increased with the severity of the dengue infection and are strongly associated with various clinical manifestations. Thus, PAR-1 levels can be used as a diagnostic marker for assessing dengue severity.     

Changes in levels of anti-dengue virus IgG subclasses in patients with disease of varying severity

Extensive complement activation precedes onset of shock in dengue patients and complement "split products" C3a and C5a could be responsible, directly or indirectly, for the increased vascular permeability and disseminated intravascular coagulation which characterises dengue haemorrhagic fever (DHF) dengue shock syndrome (DSS). As IgG subclasses vary in their capacity to activate the classical complement pathway after combining with antigen, we have used an indirect enzyme linked immunosorbent assay (ELISA) to assess levels of lgG1–4 against each dengue serotype in acute and convalescent sera from patients with disease of varying severity. Acute phase sera from patients with dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS) contained higher levels of anti-dengue antibodies of the IgG1, complement fixing, subclass than similar sera from dengue fever (DF) patients. Conversely, acute phase sera from DHF and DSS patients contained lower levels of anti-dengue antibodies of the poor complement activating lgG2 subclass than acute phase sera from DF patients. No significant differences were detected between the levels of anti-dengue lgG3 and lgG4 antibody in acute phase sera from DF, DHF, and DSS patients. With the exception of levels of antidengue lgG2 antibody from DHF patients which were lower than those from DF and DSS patients, levels of anti-dengue IgG1, lgG2, lgG3, and lgG4 were similar in convalescent sera from all patients. These results Provide a possible explanation for the activation of the serum complement system which precedes onset of shock in severe dengue infections. © 1993 Wiley-Liss, Inc.     

Impact of multi-drug-resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> on clinical outcomes

We conducted a retrospective matched cohort study to examine the impact of isolation of multi-drug-resistant (MDR) Acinetobacter baumannii on patient outcomes. Cases from whom MDR A. baumannii was isolated in a clinical culture (n = 118) were compared with controls from whom MDR A. baumannii was not isolated (n = 118). Cases and controls were matched according to ward, calendar month of hospitalization, and duration of hospitalization before culture. The following outcomes were compared in multivariable analysis: in-hospital mortality, length of stay, need for mechanical ventilation, and functional status at discharge. MDR A. baumannii was determined to be a pathogen in 72% of cases. In 36% of cases, the patient died, versus 21% of controls (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.17–4.16, P = 0.014). Median length of stay for surviving cases was 17 days, versus 11 for surviving controls (multiplicative effect 1.55, 95% CI 0.99–2.44, P = 0.057). Fifty-two percent of cases required mechanical ventilation, versus 25% of controls (OR 3.72, 95% CI 1.91–7.25, P<0.001); 60% of surviving cases were discharged with reduced functional status, versus 38% of controls (OR 4.4, 95% CI 1.66–11.61, P = 0.003). In multivariable analysis, clinical isolation of MDR A. baumannii remained a significant predictor of mortality (OR 6.23, 95% CI 1.31–29.5, P = 0.021), need for mechanical ventilation (OR 7.34, 95% CI 2.24–24.0, P<0.001), and reduced functional status on discharge (OR 7.93, 95% CI 1.1–56.85, P = 0.039). Thus, MDR A. baumannii acquisition is associated with severe adverse outcomes, including increased mortality, need for mechanical ventilation, and reduced functional status.     

No association of TAP2 polymorphisms in Korean patients with schizophrenia

OBJECTIVES: Polymorphisms of transporters associated with antigen-processing (TAP) genes might influence the susceptibility to schizophrenia by altering the antigen-processing pathway. The aim of this study was to verify the relationship between schizophrenia and the polymorphisms of TAP2 genes. METHOD: Two hundred and fifty-seven Korean patients diagnosed with schizophrenia according to DSM-IV and 184 normal controls participated in this study. TAP2 polymorphic residues at positions 379, 565 and 665 were typed using amplification refractory mutation system-polymerase chain reaction single-strand conformation polymorphism. RESULTS: Distribution of the alleles and genotypes in patients with schizophrenia was not significantly different from those of controls. CONCLUSIONS: This study did not show the association of the TAP2 gene with schizophrenia in the Korean population.     

TAP1 and TAP2 gene polymorphisms in Korean patients with allergic rhinitis

Antigen peptides are actively transported across the endoplasmic reticulum by the transporters associated with antigen presentation (TAP). TAP genes polymorphism could influence the selection process that determines which antigen peptides play a role in the pathogenesis of allergic rhinitis. The aim of this study was to investigate the association of TAP genes polymorphism with allergic rhinitis. TAP1 and TAP2 genotyping were performed on 110 allergic rhinitis patients and 107 healthy controls. TAP1 polymorphic residues at codons 333 and 637, and TAP2 polymorphic residues at codons 379, 565, 651, and 665 were analyzed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Analysis of TAP1 gene polymorphism demonstrated decreased frequencies of Ile/Val genotype at codon 333, Asp/Gly genotype at codon 637, and haplotype A and B in allergic rhinitis patients when compared to controls (p<0.05). However, there was no significant difference in the genotype, phenotype, or allele frequencies at four TAP2 codons between controls and allergic rhinitis patients. In conclusion, TAP1 gene polymorphism may be an important factor contributing to the genetic susceptibility in the development of allergic rhinitis in the Korean population.     

Serum nitric oxide in children with dengue infection

One hundred and ten patients (M/F = 67/43) from King Chulalongkorn Memorial Hospital and the provincial hospitals of Uttaradit, Ayudhaya, and Sakonnakorn, who were clinically diagnosed with dengue infection and serologically confirmed by ELISA anti-Dengue IgM and IgG were recruited. Their serum NO level was measured using commercially available assay kits to investigate its correlation with the severity of the dengue infection: dengue fever (DF), DHF I/II, and DHF III/IV or dengue shock syndrome (DSS). Serum NO levels were also measured in 38 healthy controls (M/F = 19/19). Serum NO levels in dengue patients were lower than those of the controls (control = 168.18 +/- 24.10 micromol/l, DF = 124.94 +/- 36.79 micromol/l, DHF I/II = 99.69 +/- 33.42 micromol/l, and DHF III/IV = 120.63 +/- 46.26 micromol/l; p < 0.05). Serum NO levels in patients with DHF I/II were significantly lower than in those with DHF III/IV. These preliminary data revealed that levels of serum NO in dengue patients were significantly lower than those of normal controls. Patients with DSS had higher NO levels than those with DHF I/II. The decreased NO in dengue patients could be due to endothelial damage rendering the endothelium incapable of producing NO. Endothelial function seems to play a role in the pathogenesis of dengue infection. Further studies are required to see whether serum NO levels could play a role in the course of the disease and could help predict the severity of dengue infection.     

KIR copy number variations in dengue-infected patients from northeastern Thailand

Killer immunoglobulin-like receptors (KIRs) are a family of receptors expressed on Natural killer (NK) cells. The extensive polymorphism of KIR is involved in the immune responses of NK cells and influences dengue infections. We investigated the diversity of KIR copy numbers in dengue-infected patients from northeastern Thailand. Copy numbers of KIRs were determined by quantitative polymerase chain reaction in 137 dengue-infected patients, comprising 63 dengue fever (DF) and 74 dengue hemorrhagic fever (DHF). The distribution of KIRs was observed to be between 0 and 4 copies. The KIR AA genotype with heterozygous KIR2DS4D/WT was the most common in dengue patients, 25.4% DF and 23% DHF. Forty KIR profiles were determined in dengue patients, including 31 usual, 6 expanded, and 3 contracted profiles. Investigation of KIR copy number and dengue severity indicated that two copies of KIR2DL3 combined with HLA-C1C1 associated with an increased risk of DHF (OR 2.32, 95% CI 1.159–4.624, P = 0.016), whereas one copy of KIR2DL2 and KIR2DL3 together with HLA-C1C1 associated with a reduced risk of DHF (OR 0.17, 95% CI 0.058–0.482, P < 0.001). The outcomes of this study will contribute to the understanding of KIR complexity and innate immune responses in dengue infections.