Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge... more Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge on how the virus remodels the metabolic and immune response toward hepatic pathologic environment is limited. The transcriptomic and multiple evidences reveal that the HCV core protein–intestine‐specific homeobox (ISX) axis promotes a spectrum of metabolic, fibrogenic, and immune modulators (e.g., kynurenine, PD‐L1, and B7‐2), regulating HCV‐infection relevant pathogenic phenotype in vitro and in vivo. In a transgenic mice model, the HCV core protein–ISX axis enhance metabolic disturbance (particularly lipid and glucose metabolism) and immune suppression, and finally, chronic liver fibrosis in a high‐fat diet (HFD)‐induced disease model. Mechanistically, cells with HCV JFH‐1 replicons upregulate ISX and, consequently, the expressions of metabolic, fibrosis progenitor, and immune modulators via core protein‐induced nuclear factor‐κB signaling. Conversely, cells with specific ISX shRNAi inhibit HCV core protein‐induced metabolic disturbance and immune suppression. Clinically, the HCV core level is significantly correlated with ISX, IDOs, PD‐L1, and B7‐2 levels in HCC patients with HCV infection. Therefore, it highlights the significance of HCV core protein–ISX axis as an important mechanism in the development of HCV‐induced chronic liver disease and can be a specific therapeutic target clinically.
Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, ... more Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled LTB4, characterizes childhood asthma. While FeNO has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15-HETE, but not TXB2, showed significant difference between asthmatics (N=318) and healthy controls (N=97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver Operating Characteristic (ROC) analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 and FeNO, whilethe 15-HETE/LTB4 ratio was significantly lower in subjects with severe asthma (p<0.01). Analysis of asthmatics (N=75) during exacerbation and convalescence showed significant improvement in lung function (FEV1; p<0.001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p<0.001) and reduced levels of TXB2 (p<0.05) after therapy, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and LXA4 at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15-HETE were prominent after treatment.
International Journal of Molecular Sciences, Apr 11, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Hung C-H. Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigene... more Hung C-H. Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation. Allergy 2013;
The Journal of Allergy and Clinical Immunology, Feb 1, 2017
RATIONALE: Asthma is a heterogeneous chronic pulmonary inflammatory disease, commonly preceded by... more RATIONALE: Asthma is a heterogeneous chronic pulmonary inflammatory disease, commonly preceded by atopic dermatitis (AD). We have recently shown that systemic IL-22 is induced by epicutaneous (EC) sensitization in a mouse model of AD. We examined whether this IL-22 response contributes to airway inflammation triggered by antigen inhalation in EC sensitized mice. METHODS: Wild type (WT) and Il22-/mice were subjected to EC sensitization with ovalbumin (OVA) or saline followed by intranasal (i.n.) OVA challenge. WT mice were adoptively transferred with OVA TCR-specific Th22 from WT or Il22-/mice and i.n. challenged with OVA. rIL-22, rIL-17A and rTNFa, alone or in combination were instilled intranasally in WT mice. Airway inflammation, mRNA levels in the lungs and airway hyperresponsiveness (AHR) were examined. RESULTS: EC OVA sensitization promoted IL-22 production in the lungs after i.n. challenge. EC OVA sensitized Il22-/mice exhibited diminished eosinophil and neutrophil airway infiltration and decreased AHR following i.n. OVA challenge. Moreover, Il22-/mice exhibited enhanced IFNg, but normal IL-13 and IL-17 production in the lungs. Adoptive transfer of in vitro polarized WT but not IL-22 deficient TCR-OVA specific Th22 cells, which co-express IL-17A and TNFa, promoted a neutrophil-dominated airway inflammation, increased Cxcl1 and Cxcl3 mRNA and enhanced AHR. Intranasal instillation of IL-22 in combination with TNFa, but not IL-17A, caused neutrophilic airway inflammation with increased Cxcl1 and Cxcl3 mRNA and enhanced AHR. CONCLUSIONS: EC sensitization promotes the generation of antigenspecific Th22 cells, which drive neutrophil-dominated airway inflammation and AHR following antigen inhalation, suggesting that IL-22 plays an important role in the atopic march.
SummaryBackground The molecular and functional basis of allergen‐induced inflammation seen in ato... more SummaryBackground The molecular and functional basis of allergen‐induced inflammation seen in atopic dermatitis (AD) remains undefined.Objective The objective of this study is to establish a murine model to dissect the pathological mechanisms of inflammatory reactions leading to the development of AD.Methods An inbred strain of mice. BALB/c, when injected peritoneally with 30 μg of recombinant Sj26 protein (rSj26). a glutathione S‐transferase of Schistosoma japonicum worm, developed systematic dermatitis 21 days after immunization. The pathology of the dermatitis was examined by histological evaluation and immunostaining. The immediate skin hypersensitivity was demonstrated by scrum transfer and skin test. Epicutaneous patch test was used to demonstrate the antigen‐specific late phase response.Results Significant responses of rSj26‐specific IgE were detected 2 weeks after immunization., and such changes paralleled formation of skin lesions. The diseased skin pathology showed inflammatory changes such as infiltration of mononuclear cells and eosinophils in the dermis and mild spongiosis in the epidermis. Numerous IgE bearing cells were also detected in the dermis. Peripheral blood showed eosinophilia at the same time. In addition, rSj26‐specific positive skin test and epicutaneous patch test could be demonstrated in rSj26‐sensitized mice.Conclusions These results suggest that rSj26 is capable of eliciting atopic dermatitis‐like lesions in BALB/c mice. This can be a useful animal model for elucidating allergen‐induced immune responses and the development of various therapeutic interventions of atopic dermatitis in humans.
The Journal of Allergy and Clinical Immunology, May 1, 2023
BackgroundTimely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and ... more BackgroundTimely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease’s pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging.ObjectiveWe investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression.MethodsWe performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease.ResultsPhospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models.ConclusionSignificant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19’s severity and pathogenesis.
Background: Aberrant generation of eicosanoids is associated with asthma, but the evidence remain... more Background: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. Methods: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. Results: Exhaled LTB 4 , LTE 4 , PGE 2 and LXA 4 showed significant difference between asthmatics (N=60) and controls (N=20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls were partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver Operating Characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB 4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB 4 , LXA 4 , together with FeNO and FEV 1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma Accepted Article This article is protected by copyright. All rights reserved. classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. Conclusions: In a pediatric study population in Taiwan, the levels of exhaled LTB 4 , LTE 4 , LXA 4 and PGE 2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB 4 and LXA 4 , together with FeNO and FEV 1 , best characterized childhood asthma.
Specific immune responsiveness to the Amb a V allergen (from Ambrosia artemisiifolia, short ragwe... more Specific immune responsiveness to the Amb a V allergen (from Ambrosia artemisiifolia, short ragweed pollen) is significantly associated with the Class II specificities, human leucocyte antigen (HLA)-DR2 and Dw2 determined by serological and MLR typing ("DR2.2"). Similarly, responsiveness to homologous Amb t V and Amb p V allergens is associated with DR2.2. We examined the deoxyribonucleic acid (DNA) sequences of HLA-DRB1, DRB5, DQB1 and DQA1 genes associated with Amb a V responsiveness using a combination of polymerase chain reaction (PCR), dot-blot and DNA sequencing methodologies. Our focus was on the highly polymorphic regions within the second-exon gene segments that are believed to encode antigen (Ag)-binding portions of the respective Class II molecules. Analysis of three patients having unusual sequence combinations of HLA-D gene sequences implicate an HLA-DR molecule (either DR alpha beta I 2.2 or DR alpha beta V 2.2), rather than a DQ Class II molecule, as the major Amb a V immune response (Ir) gene product. Our studies suggest that this DR2.2 molecule is usually a necessary, and almost always a sufficient, requirement for high immunoglobulin E and G (IgE) and (IgG) antibody responsiveness in ragweed-allergic individuals. From an atopic DR2.2+ subject, we isolated three Amb a V-specific T-cell clones. Analysis revealed these clones to be DR-restricted, supporting the conclusion that the Amb a V-Ir gene is a DR and not a DQ molecule. The DR beta I polypeptide of DR2.2 and 2.12 was implicated in Ag presentation, since monoclonal antibody (MoAb) Hu30 (antibody specific for DR beta I) blocked T-cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might ... more We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-b1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-b1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-b1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-b1 may play a key role in COVID-19.
Cold Spring Harbor Symposia on Quantitative Biology, 1989
Atopic allergy is a common disease that provides an appropriate model for studying the genetic an... more Atopic allergy is a common disease that provides an appropriate model for studying the genetic and molecular basis of human immune responsiveness and its relationship to immunological disease (Marsh 1975; Marsh et al. 1981). In the case of allergy, unlike most other immunological diseases, a clear causal relationship has been established between specific immune responsiveness (detected by the presence of serum IgE antibodies) and the expression of a specific atopic disease. A large number of highly purified, well-characterized allergens are now available, and many more identified allergens await characterization (Marsh et al. 1986; Marsh and Norman 1988). Especially in the case of allergy to inhaled antigens, natural exposure is toward immunogenically limiting antigen doses (typically less than 1 μ g/year [Marsh 1975]), which facilitates the study of Ir genes. Immunization with much higher doses of antigen than encountered by natural exposure forms the basis of conventional allergen immunotherapy (Rx).
Arsenic induces multiple Bowen's disease (As-BD), or cutaneous carcinoma in situ, that runs a... more Arsenic induces multiple Bowen's disease (As-BD), or cutaneous carcinoma in situ, that runs an indolent course. Immune responses are important modifiers for the development of As-BD. We have previously reported that Langerhans cells (LCs) were reduced in As-BD, but how arsenic alters LC migration and polarizes Th responses remains unknown. Using an epicutaneous protein sensitization model, Balb/c mice were patch-sensitized with OVA and received feeding of 300 ppm arsenic or PBS for 200ul for 5 days. Defined as CD207+MHCII+ cells, the number of LCs was significantly decreased in patched epidermis, but increased in draining lymph nodes, with no changes in dermis and spleens 96 hours after OVA sensitization in arsenic-treated mice. There was a parallel increase of CCL21 in lymph nodes from arsenic-treated mice, and enhanced cellular proliferation and IFN-γ secretion in vitro were also noted in lymph node cells from arsenic-treated mice. Notably, in vivo administration of a neutralizing antibody against CCL21 abolished the increase of LCs in lymph nodes. These results suggest, therefore, that in this model, arsenic exposure enhanced LC migration to draining lymph nodes via CCL21 and interferon-γ production, and that chronic nature of As-BD might result from enhanced Th1 responses and LC migration.
Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge... more Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge on how the virus remodels the metabolic and immune response toward hepatic pathologic environment is limited. The transcriptomic and multiple evidences reveal that the HCV core protein–intestine‐specific homeobox (ISX) axis promotes a spectrum of metabolic, fibrogenic, and immune modulators (e.g., kynurenine, PD‐L1, and B7‐2), regulating HCV‐infection relevant pathogenic phenotype in vitro and in vivo. In a transgenic mice model, the HCV core protein–ISX axis enhance metabolic disturbance (particularly lipid and glucose metabolism) and immune suppression, and finally, chronic liver fibrosis in a high‐fat diet (HFD)‐induced disease model. Mechanistically, cells with HCV JFH‐1 replicons upregulate ISX and, consequently, the expressions of metabolic, fibrosis progenitor, and immune modulators via core protein‐induced nuclear factor‐κB signaling. Conversely, cells with specific ISX shRNAi inhibit HCV core protein‐induced metabolic disturbance and immune suppression. Clinically, the HCV core level is significantly correlated with ISX, IDOs, PD‐L1, and B7‐2 levels in HCC patients with HCV infection. Therefore, it highlights the significance of HCV core protein–ISX axis as an important mechanism in the development of HCV‐induced chronic liver disease and can be a specific therapeutic target clinically.
Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, ... more Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled LTB4, characterizes childhood asthma. While FeNO has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15-HETE, but not TXB2, showed significant difference between asthmatics (N=318) and healthy controls (N=97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver Operating Characteristic (ROC) analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 and FeNO, whilethe 15-HETE/LTB4 ratio was significantly lower in subjects with severe asthma (p<0.01). Analysis of asthmatics (N=75) during exacerbation and convalescence showed significant improvement in lung function (FEV1; p<0.001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p<0.001) and reduced levels of TXB2 (p<0.05) after therapy, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and LXA4 at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15-HETE were prominent after treatment.
International Journal of Molecular Sciences, Apr 11, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Hung C-H. Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigene... more Hung C-H. Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation. Allergy 2013;
The Journal of Allergy and Clinical Immunology, Feb 1, 2017
RATIONALE: Asthma is a heterogeneous chronic pulmonary inflammatory disease, commonly preceded by... more RATIONALE: Asthma is a heterogeneous chronic pulmonary inflammatory disease, commonly preceded by atopic dermatitis (AD). We have recently shown that systemic IL-22 is induced by epicutaneous (EC) sensitization in a mouse model of AD. We examined whether this IL-22 response contributes to airway inflammation triggered by antigen inhalation in EC sensitized mice. METHODS: Wild type (WT) and Il22-/mice were subjected to EC sensitization with ovalbumin (OVA) or saline followed by intranasal (i.n.) OVA challenge. WT mice were adoptively transferred with OVA TCR-specific Th22 from WT or Il22-/mice and i.n. challenged with OVA. rIL-22, rIL-17A and rTNFa, alone or in combination were instilled intranasally in WT mice. Airway inflammation, mRNA levels in the lungs and airway hyperresponsiveness (AHR) were examined. RESULTS: EC OVA sensitization promoted IL-22 production in the lungs after i.n. challenge. EC OVA sensitized Il22-/mice exhibited diminished eosinophil and neutrophil airway infiltration and decreased AHR following i.n. OVA challenge. Moreover, Il22-/mice exhibited enhanced IFNg, but normal IL-13 and IL-17 production in the lungs. Adoptive transfer of in vitro polarized WT but not IL-22 deficient TCR-OVA specific Th22 cells, which co-express IL-17A and TNFa, promoted a neutrophil-dominated airway inflammation, increased Cxcl1 and Cxcl3 mRNA and enhanced AHR. Intranasal instillation of IL-22 in combination with TNFa, but not IL-17A, caused neutrophilic airway inflammation with increased Cxcl1 and Cxcl3 mRNA and enhanced AHR. CONCLUSIONS: EC sensitization promotes the generation of antigenspecific Th22 cells, which drive neutrophil-dominated airway inflammation and AHR following antigen inhalation, suggesting that IL-22 plays an important role in the atopic march.
SummaryBackground The molecular and functional basis of allergen‐induced inflammation seen in ato... more SummaryBackground The molecular and functional basis of allergen‐induced inflammation seen in atopic dermatitis (AD) remains undefined.Objective The objective of this study is to establish a murine model to dissect the pathological mechanisms of inflammatory reactions leading to the development of AD.Methods An inbred strain of mice. BALB/c, when injected peritoneally with 30 μg of recombinant Sj26 protein (rSj26). a glutathione S‐transferase of Schistosoma japonicum worm, developed systematic dermatitis 21 days after immunization. The pathology of the dermatitis was examined by histological evaluation and immunostaining. The immediate skin hypersensitivity was demonstrated by scrum transfer and skin test. Epicutaneous patch test was used to demonstrate the antigen‐specific late phase response.Results Significant responses of rSj26‐specific IgE were detected 2 weeks after immunization., and such changes paralleled formation of skin lesions. The diseased skin pathology showed inflammatory changes such as infiltration of mononuclear cells and eosinophils in the dermis and mild spongiosis in the epidermis. Numerous IgE bearing cells were also detected in the dermis. Peripheral blood showed eosinophilia at the same time. In addition, rSj26‐specific positive skin test and epicutaneous patch test could be demonstrated in rSj26‐sensitized mice.Conclusions These results suggest that rSj26 is capable of eliciting atopic dermatitis‐like lesions in BALB/c mice. This can be a useful animal model for elucidating allergen‐induced immune responses and the development of various therapeutic interventions of atopic dermatitis in humans.
The Journal of Allergy and Clinical Immunology, May 1, 2023
BackgroundTimely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and ... more BackgroundTimely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease’s pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging.ObjectiveWe investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression.MethodsWe performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease.ResultsPhospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models.ConclusionSignificant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19’s severity and pathogenesis.
Background: Aberrant generation of eicosanoids is associated with asthma, but the evidence remain... more Background: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. Methods: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. Results: Exhaled LTB 4 , LTE 4 , PGE 2 and LXA 4 showed significant difference between asthmatics (N=60) and controls (N=20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls were partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver Operating Characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB 4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB 4 , LXA 4 , together with FeNO and FEV 1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma Accepted Article This article is protected by copyright. All rights reserved. classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. Conclusions: In a pediatric study population in Taiwan, the levels of exhaled LTB 4 , LTE 4 , LXA 4 and PGE 2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB 4 and LXA 4 , together with FeNO and FEV 1 , best characterized childhood asthma.
Specific immune responsiveness to the Amb a V allergen (from Ambrosia artemisiifolia, short ragwe... more Specific immune responsiveness to the Amb a V allergen (from Ambrosia artemisiifolia, short ragweed pollen) is significantly associated with the Class II specificities, human leucocyte antigen (HLA)-DR2 and Dw2 determined by serological and MLR typing ("DR2.2"). Similarly, responsiveness to homologous Amb t V and Amb p V allergens is associated with DR2.2. We examined the deoxyribonucleic acid (DNA) sequences of HLA-DRB1, DRB5, DQB1 and DQA1 genes associated with Amb a V responsiveness using a combination of polymerase chain reaction (PCR), dot-blot and DNA sequencing methodologies. Our focus was on the highly polymorphic regions within the second-exon gene segments that are believed to encode antigen (Ag)-binding portions of the respective Class II molecules. Analysis of three patients having unusual sequence combinations of HLA-D gene sequences implicate an HLA-DR molecule (either DR alpha beta I 2.2 or DR alpha beta V 2.2), rather than a DQ Class II molecule, as the major Amb a V immune response (Ir) gene product. Our studies suggest that this DR2.2 molecule is usually a necessary, and almost always a sufficient, requirement for high immunoglobulin E and G (IgE) and (IgG) antibody responsiveness in ragweed-allergic individuals. From an atopic DR2.2+ subject, we isolated three Amb a V-specific T-cell clones. Analysis revealed these clones to be DR-restricted, supporting the conclusion that the Amb a V-Ir gene is a DR and not a DQ molecule. The DR beta I polypeptide of DR2.2 and 2.12 was implicated in Ag presentation, since monoclonal antibody (MoAb) Hu30 (antibody specific for DR beta I) blocked T-cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might ... more We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-b1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-b1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-b1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-b1 may play a key role in COVID-19.
Cold Spring Harbor Symposia on Quantitative Biology, 1989
Atopic allergy is a common disease that provides an appropriate model for studying the genetic an... more Atopic allergy is a common disease that provides an appropriate model for studying the genetic and molecular basis of human immune responsiveness and its relationship to immunological disease (Marsh 1975; Marsh et al. 1981). In the case of allergy, unlike most other immunological diseases, a clear causal relationship has been established between specific immune responsiveness (detected by the presence of serum IgE antibodies) and the expression of a specific atopic disease. A large number of highly purified, well-characterized allergens are now available, and many more identified allergens await characterization (Marsh et al. 1986; Marsh and Norman 1988). Especially in the case of allergy to inhaled antigens, natural exposure is toward immunogenically limiting antigen doses (typically less than 1 μ g/year [Marsh 1975]), which facilitates the study of Ir genes. Immunization with much higher doses of antigen than encountered by natural exposure forms the basis of conventional allergen immunotherapy (Rx).
Arsenic induces multiple Bowen's disease (As-BD), or cutaneous carcinoma in situ, that runs a... more Arsenic induces multiple Bowen's disease (As-BD), or cutaneous carcinoma in situ, that runs an indolent course. Immune responses are important modifiers for the development of As-BD. We have previously reported that Langerhans cells (LCs) were reduced in As-BD, but how arsenic alters LC migration and polarizes Th responses remains unknown. Using an epicutaneous protein sensitization model, Balb/c mice were patch-sensitized with OVA and received feeding of 300 ppm arsenic or PBS for 200ul for 5 days. Defined as CD207+MHCII+ cells, the number of LCs was significantly decreased in patched epidermis, but increased in draining lymph nodes, with no changes in dermis and spleens 96 hours after OVA sensitization in arsenic-treated mice. There was a parallel increase of CCL21 in lymph nodes from arsenic-treated mice, and enhanced cellular proliferation and IFN-γ secretion in vitro were also noted in lymph node cells from arsenic-treated mice. Notably, in vivo administration of a neutralizing antibody against CCL21 abolished the increase of LCs in lymph nodes. These results suggest, therefore, that in this model, arsenic exposure enhanced LC migration to draining lymph nodes via CCL21 and interferon-γ production, and that chronic nature of As-BD might result from enhanced Th1 responses and LC migration.
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