RESUMO
OBJECTIVE: The identification of allergic rhinitis (AR) in early life is important for the target of intervention. AR is caused by various environmental factors, including house dust mites. We investigated the relationship between the Dermatophagoides farinae (Der f)-IgE and eosinophil in mothers with AR at delivery and the eosinophil levels and AR incidence in children. METHODS: The study participants were 983 mother-child pairs from the COhort for Childhood Origin of Asthma and Allergic Diseases. AR was diagnosed by a doctor at delivery in mother and at 3 years of age in offspring. The association between eosinophil level and AR was assessed using logistic regression analysis. RESULTS: The Der f-IgE level in mother having AR at delivery was associated with the mother's eosinophil level, and the mother's eosinophil level was associated with the child's eosinophil level both at age 1 and 3. The risk of AR at age 3 in children was increased according to increased eosinophil levels in mothers at delivery and in children both aged 1 and 3 years (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 2.57 [1.14-5.78], 2.28 [1.02-5.13], respectively). The risk of childhood AR at the age of 3 is increased when both mothers and children have high eosiniophils (aOR and 95% CI: 2.62 [1.01-6.79], 1.37 [0.98-1.91]). CONCLUSIONS: Der f-IgE in mothers at delivery was related to eosinophil levels in mothers with AR and higher level of eosinophils in both mother and children was associated with the increased risk of AR incidence at the first 3 years of life of children.
Assuntos
Asma , Rinite Alérgica , Feminino , Humanos , Lactente , Pré-Escolar , Eosinófilos , Incidência , Imunoglobulina E , Rinite Alérgica/epidemiologia , Asma/epidemiologia , Asma/etiologia , Asma/diagnósticoRESUMO
BACKGROUND: Various cytokines have been studied to determine their functions in the pathogenesis of allergic diseases and their potential as therapeutic targets, but the roles and clinical applicability of many of these cytokines still remain unclear. OBJECTIVE: We aimed to measure the plasma levels of eight cytokines known to be relevant to allergic diseases, and to determine their association with the diagnostic characteristics of allergic patients. METHODS: The levels of a panel of eight cytokines (IL-5, IL-10, IL12p70, Leptin, CXCL5/ENA-78, CCL2/MCP-1, PDGFBB, and VEGF) were measured in plasma obtained from 83 allergic patients. We investigated whether the cytokine levels differed between children and adults. Statistical analyses were then performed to examine their association with the diagnostic characteristics of allergic patients. RESULTS: The levels of leptin, CCL2/MCP-1, PDGFBB, and VEGF were significantly higher in adult patients with allergic rhinitis than in children. Among patients with asthma, the levels of leptin and PDGFBB were elevated in adults. PDGFBB and VEGF levels were significantly associated with asthma. Interestingly, there was a significant association between VEGF level and recurrent wheezing regardless of the analyzed conditions. The levels of VEGF and PDGFBB or CCL2/MCP-1 showed a significant increase together in the presence of recurrent wheezing in child patients. CONCLUSIONS: The plasma levels of four cytokines, particularly VEGF, showed significant associations with some diagnostic characteristics in allergic patients. We suggested that plasma VEGF, which performs pleiotropic functions in allergic responses, could serve as a serological marker relevant to recurrent wheezing in allergic patients.
Assuntos
Asma , Rinite Alérgica , Adulto , Asma/diagnóstico , Criança , Citocinas , Humanos , Sons Respiratórios , Rinite Alérgica/diagnóstico , Fator A de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. METHODS: A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. RESULTS: The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. CONCLUSIONS: The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.
Assuntos
Asma , Rinite Alérgica , Alérgenos , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologia , Criança , Humanos , República da Coreia/epidemiologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Testes CutâneosRESUMO
BACKGROUND: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). METHODS: Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. RESULTS: A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). CONCLUSIONS: A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.
Assuntos
Rinite Alérgica , Verduras , Criança , Dieta , Humanos , Fenótipo , Rinite Alérgica/epidemiologia , Rinite Alérgica/genética , Rinite Alérgica/prevenção & controle , Fatores de Risco , Instituições AcadêmicasRESUMO
Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma.Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations.Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score.Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.
Assuntos
Asma/diagnóstico , Índice de Gravidade de Doença , Adolescente , Asma/sangue , Asma/fisiopatologia , Proteína C-Reativa/análise , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/fisiopatologia , Contagem de Leucócitos , Pulmão/fisiopatologia , Masculino , Óxido Nítrico/análiseRESUMO
BACKGROUND: Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. METHODS: We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects' baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. DISCUSSION: Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects' personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.
Assuntos
Asma/fisiopatologia , Progressão da Doença , Adolescente , Testes de Provocação Brônquica , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Pico do Fluxo Expiratório , Estudos Prospectivos , República da Coreia , Fatores de Risco , Espirometria , Inquéritos e QuestionáriosRESUMO
This research examined how information-seeking tactics and sense of workplace community are related to one another. Data from Korea showed that workers (n = 314) who preferred overt tactics of seeking information (i.e., direct questioning) also reported a stronger sense of workplace community. Information types and sources did not moderate the relationship between information-seeking tactics and sense of workplace community. Information types, however, moderated the relationship between importance of information and sense of workplace community and the relationship between coworker availability as an information source and sense of workplace community.
Assuntos
Comportamento de Busca de Informação , Relações Interpessoais , Identificação Social , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , República da Coreia , Adulto JovemRESUMO
BACKGROUND: Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic dermatitis (AD) risk remains poorly understood. OBJECTIVE: We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species. METHODS: Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases [COCOA]) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children [PSKC]) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11ß-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured. RESULTS: In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 [95% CI, 1.02-1.69]; hazard ratio for anxiety, 1.41 [95% CI, 1.06-1.89]) and PSKC (odds ratio for distress, 1.85 [95% CI, 1.06-3.25]). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD (P < .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios (P = .037) and, especially in those who later had AD, decreased placental 11ß-hydroxysteroid dehydrogenase type 2 levels (P = .010) and increased IgE levels at 1 year of age (P = .005). CONCLUSION: Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.
Assuntos
Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Estresse Fisiológico , Estresse Psicológico , Adulto , Biomarcadores , Pré-Escolar , Comorbidade , Dermatite Atópica/epidemiologia , Feminino , Humanos , Lactente , Masculino , Exposição Materna/efeitos adversos , Pessoa de Meia-Idade , Razão de Chances , Estresse Oxidativo , Gravidez , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto JovemRESUMO
Genetic and epigenetic programming of T helper (Th) cell subsets during their polarization from naive Th cells establishes long-lived memory Th cells that stably maintain their lineage signatures. However, whether memory Th cells can be redifferentiated into another Th lineage is unclear. In this study, we show that Ag-specific memory Th cells were redifferentiated into Foxp3(+) T cells by TGF-beta when stimulated in the presence of all-trans retinoic acid and rapamycin. The "converted" Foxp3(+) T cells that were derived from Th2 memory cells down-regulated GATA-3 and IRF4 and produced little IL-4, IL-5, and IL-13. Instead, the converted Foxp3(+) T cells suppressed the proliferation and cytokine production of Th2 memory cells. More importantly, the converted Foxp3(+) T cells efficiently accumulated in the airways and significantly suppressed Th2 memory cell-mediated airway hyperreactivity, eosinophilia, and allergen-specific IgE production. Our findings reveal the plasticity of Th2 memory cells and provide a strategy for adoptive immunotherapy for the treatment of allergic diseases.
Assuntos
Asma/imunologia , Fatores de Transcrição Forkhead/imunologia , Memória Imunológica/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Animais , Asma/complicações , Asma/fisiopatologia , Hiper-Reatividade Brônquica/complicações , Hiper-Reatividade Brônquica/imunologia , Citocinas/metabolismo , Eosinófilos/imunologia , Eosinófilos/patologia , Epitopos/imunologia , Feminino , Fator de Transcrição GATA3/metabolismo , Memória Imunológica/efeitos dos fármacos , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Sirolimo/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologia , Células Th2/efeitos dos fármacos , Células Th2/patologia , Fator de Crescimento Transformador beta/farmacologia , Tretinoína/farmacologiaRESUMO
Background: Atopic march (AM), a unique characteristic of allergic diseases, refers to the sequential progression of atopic dermatitis (AD) in infants to allergic asthma and allergic rhinitis in children and young adults, respectively. Although there are several studies on AM, the establishment of an AM murine model to expand our understanding of the underlying mechanism and to identify the potential biomarkers is yet to be achieved. In this study, an improved murine model was established by applying a method to minimize skin irritation in inducing AD, and it was used to perform integrated analyses to discover candidate biomarkers. Methods: To induce atopic dermatitis, 2,4-dinitrochlorobenzene (DNCB) was applied to the ear skin once a week, and this was continued for 5 weeks. From the second application of DNCB, Dermatophagoides pteronyssinus (Dp) extract was applied topically 2 days after each DNCB application; this was continued for 4 weeks. Dp sensitization and intranasal challenges were then performed for 4 weeks to develop conditions mimicking AM. Results: Exacerbated airway inflammation and allergic responses observed in the AM-induced group suggested successful AM development in our model. Two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis identified 753 candidate proteins from 124 2-DE spots differentially expressed among the experimental groups. Functional analyses, such as Gene Ontology (GO) annotation and protein-protein interaction (PPI) analysis were conducted to investigate the relationship among the candidate proteins. Seventy-two GO terms were significant between the two groups; heat shock protein 8 (Hspa8) was found to be included in six of the top 10 GO terms. Hspa8 scored high on the PPI parameters as well. Conclusion: We established an improved murine model for AM and proposed Hspa8 as a candidate biomarker for AM.
Assuntos
Dermatite Atópica , Proteínas de Choque Térmico , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dinitroclorobenzeno/efeitos adversos , Modelos Animais de Doenças , Proteínas de Choque Térmico/metabolismo , PeleRESUMO
The bone and dentin have distinct healing processes. The healing process of bones is regenerative, as newly formed tissues are morphologically and functionally similar to the original bone structures. In contrast, the healing process of dentin is reparative due to its failure to replicate some of its key morphological features. In this review, we compare and contrast the healing processes of bone and dentin. We describe how distinct morphological and physiological structures of the 2 tissues translate into different signaling molecules, growth factors, and matrix protein secretion.
RESUMO
Invariant NKT (iNKT) cells are a distinct subset of T lymphocytes that recognize glycolipid Ags. Upon TCR stimulation, iNKT cells promptly secrete a wide range of cytokines and therefore have been investigated as a target for immunotherapy. However, after primary activation, iNKT cells become hyporesponsive toward their ligand (anergy). The further mechanism behind iNKT cell anergy is poorly understood. We found that a low level of programmed death-1 (PD-1) was constitutively expressed on iNKT cells and that PD-1 expression was increased after stimulation and lasted at least 2 mo. Moreover, not only did blocking of the PD-1/PD ligand 1 (PD-L1) pathway prevent the induction of anergy in iNKT cells, but anergic iNKT cells also recovered responsiveness and these "rescued" cells efficiently mediated antitumor immunity. Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy.
Assuntos
Antígenos de Superfície/imunologia , Proteínas Reguladoras de Apoptose/imunologia , Antígeno B7-1/imunologia , Anergia Clonal/imunologia , Ativação Linfocitária/imunologia , Glicoproteínas de Membrana/imunologia , Peptídeos/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Antígeno B7-H1 , Citotoxicidade Imunológica , Feminino , Citometria de Fluxo , Galactosilceramidas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1RESUMO
PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
RESUMO
Her-2/neu is a well-characterized tumor-associated antigen overexpressed in human carcinomas such as breast cancer. Because Her-2/neu is a self-antigen with poor immunogenicity due to immunologic tolerance, active immunotherapy targeting Her-2/neu should incorporate methods to overcome immunologic tolerance to self-proteins. In this study, we developed a tolerogenic tumor model in mice using mouse Her-2/neu as self-antigen and investigated whether genetic vaccination with DNA plasmid and/or adenoviral vector expressing the extracellular and transmembrane domain of syngeneic mouse Her-2/neu or xenogenic human Her-2/neu could induce mouse Her-2/neu-specific CTL responses. Interestingly, adenoviral vectors expressing xenogenic human Her-2/neu (AdhHM) proved capable of breaking immune tolerance and of thereby inducing self-reactive CTL and antibodies, but not to the degree required to induce therapeutic antitumor immunity. In attempting to generate therapeutic antitumor immunity against established tumors, we adopted several approaches. Treatment with agonistic anti-glucocorticoid-induced TNFR family-related receptor (GITR) antibody plus AdhHM immunization significantly increased self-reactive CTL responses, and alpha-galactosylceramide (alphaGalCer)-loaded dendritic cells (DC) transduced with AdhHM were shown to break self-tolerance in a tolerogenic murine tumor model. Furthermore, gemcitabine treatment together with either AdhHM plus agonistic anti-GITR antibody administration or alphaGalCer-loaded DC transduced with AdhHM showed potent therapeutic antitumor immunity and perfect protection against preexisting tumors. Gemcitabine treatment attenuated the tumor-suppressive environment by eliminating CD11b(+)/Gr-1(+) myeloid-derived suppressor cells. When combined with immunotherapies, gemcitabine offers a promising strategy for the Ag-specific treatment of human cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/prevenção & controle , Neoplasias do Colo/prevenção & controle , Imunoterapia , Fragmentos de Peptídeos/imunologia , Receptor ErbB-2/imunologia , Linfócitos T Citotóxicos/imunologia , Adenoviridae/genética , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/imunologia , Antígenos de Diferenciação/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Linfócitos T CD8-Positivos/imunologia , Antígeno CTLA-4 , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Citometria de Fluxo , Galactosilceramidas/imunologia , Vetores Genéticos/administração & dosagem , Proteína Relacionada a TNFR Induzida por Glucocorticoide , Humanos , Imunização , Camundongos , Células Mieloides/citologia , Células Mieloides/imunologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/farmacologia , Receptor ErbB-2/genética , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Linfócitos T Reguladores , Taxoides/administração & dosagem , Transfecção , Vacinas de DNA/administração & dosagem , GencitabinaRESUMO
The simian immunodeficiency virus (SIV)/macaque model of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome pathogenesis is critical for furthering our understanding of the role of antibody responses in the prevention of HIV infection, and will only increase in importance as macaque immunoglobulin (IG) gene databases are expanded. We have previously reported the construction of a phage display library from a SIV-infected rhesus macaque (Macaca mulatta) using oligonucleotide primers based on human IG gene sequences. Our previous screening relied on Sanger sequencing, which was inefficient and generated only a few dozen sequences. Here, we re-analyzed this library using single molecule, real-time (SMRT) sequencing on the Pacific Biosciences (PacBio) platform to generate thousands of highly accurate circular consensus sequencing (CCS) reads corresponding to full length single chain fragment variable. CCS data were then analyzed through the international ImMunoGeneTics information system® (IMGT®)/HighV-QUEST (www.imgt.org) to identify variable genes and perform statistical analyses. Overall the library was very diverse, with 2,569 different IMGT clonotypes called for the 5,238 IGHV sequences assigned to an IMGT clonotype. Within the library, SIV-specific antibodies represented a relatively limited number of clones, with only 135 different IMGT clonotypes called from 4,594 IGHV-assigned sequences. Our data did confirm that the IGHV4 and IGHV3 gene usage was the most abundant within the rhesus antibodies screened, and that these genes were even more enriched among SIV gp140-specific antibodies. Although a broad range of VH CDR3 amino acid (AA) lengths was observed in the unpanned library, the vast majority of SIV gp140-specific antibodies demonstrated a more uniform VH CDR3 length (20 AA). This uniformity was far less apparent when VH CDR3 were classified according to their clonotype (range: 9-25 AA), which we believe is more relevant for specific antibody identification. Only 174 IGKV and 588 IGLV clonotypes were identified within the VL sequences associated with SIV gp140-specific VH. Together, these data strongly suggest that the combination of SMRT sequencing with the IMGT/HighV-QUEST querying tool will facilitate and expedite our understanding of polyclonal antibody responses during SIV infection and may serve to rapidly expand the known scope of macaque V genes utilized during these responses.
Assuntos
Anticorpos Antivirais , Especificidade de Anticorpos , Produtos do Gene env/imunologia , Biblioteca de Peptídeos , Vírus da Imunodeficiência Símia/imunologia , Anticorpos de Cadeia Única , Animais , Anticorpos Antivirais/química , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Macaca mulatta , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologiaRESUMO
PURPOSE: The prevalence of allergic diseases is known to be associated with both demographic and environmental factors. Herein, we aimed to determine significant factors associated with the prevalence of allergic diseases and with total immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea. METHODS: We analyzed unweighted data collected by the 2010 Korea National Health and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica, representing a sample of 16,003,645 citizens, by considering the sample weight and stratification. RESULTS: The overall prevalence of self-reported allergic diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic dermatitis decreased with age, whereas the asthma prevalence was not affected by the age of the subjects. When analyzed according to the type of allergic diseases, the prevalence of self-reported allergic disease was significantly associated with various factors (e.g. age, occupation, living in urban areas, and depression). The tIgE level decreased with age, but later increased. Elevation of tIgE was significantly associated with male sex, type of occupation, obesity, and smoking status. However, the risk factors for the increased sIgE levels to each allergen were quite different. Sensitization to D. farinae was more likely in young subjects, whereas the prevalence of sensitization to B. germanica was significantly higher in subjects with male sex, residing in a house (houses), and with glucose intolerance. Finally, young age and the smoking status were significantly associated with sensitization to dog. CONCLUSIONS: Various demographic and environmental factors were significantly associated with the prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to D. farinae, B. germanica, and dog in Korea.
RESUMO
PURPOSE: Allergic diseases are triggered by Th2-mediated immune reactions to allergens and orchestrated by various immunological factors, including immune cells and cytokines. Although many reports have suggested that childhood is the critical period in the onset of allergic diseases and aging leads to alter the susceptibility of an individual to allergic diseases, age-related changes in various immunological factors in healthy individuals as well as their difference between healthy and allergic children have not yet been established. METHODS: We investigated the ratio of Th1/Th2 cells and the levels of 22 allergy-related cytokines across all age groups in individuals who were classified as clinically non-atopic and healthy. We also examined their differences between healthy and allergic children to evaluate immunological changes induced by the development of allergic diseases during childhood. RESULTS: The Th1/Th2 ratio rose gradually during the growth period including childhood, reaching peak values in the twenties-thirties age group. Th1/Th2 ratios were significantly lower in allergic children than in healthy controls, whereas 14 of 22 cytokines were significantly higher in allergic children than in healthy controls. On the other hand, there were no differences in Th1/Th2 ratios and cytokines between healthy and allergic adolescents. CONCLUSIONS: In this study, age-related changes in Th1/Th2 ratios were found in normal controls across all age groups, and decreases in Th1/Th2 ratio were observed with increasing of 14 cytokines in allergic children. The results of this study may be helpful as reference values for both monitoring immunological changes according to aging in healthy individuals and distinguishing between normal and allergic subjects in terms of immune cells and soluble factors.
RESUMO
Coronary artery anomalies are rare presentations in primary percutaneous coronary interventions of acute myocardial infarction. Herein, we report the case of a 59-year-old man with acute anterior myocardial infarction who had anomalous separate origin of left anterior descending artery (LAD) and left circumflex artery (LCX) from the left coronary aortic sinus. Coronary angiography showed a normal right coronary artery and LCX, but no visualization of the LAD. After several unsuccessful attempts to cannulate the LAD, we found the LAD ostium located by the side of the LCX ostium. There was total occlusion at proxymal LAD. Coronary computed tomography angiography demonstrated the precise, separate origin of LAD and LCX from the left coronary aortic sinus.
RESUMO
How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment remains unclear. Here, we report that GM-CSF can convert natural killer (NK) cells into MDSCs. When transferred into tumor-bearing mice, adoptively transferred NK cells lost their NK phenotype and were converted into Ly6C(high)Ly6G(high) MDSC. This conversion was abolished by exposure to IL-2 either in vitro or in vivo. Notably, we found that of the 4 maturation stages based on CD11b/CD27 expression levels, only the CD11b(high)CD27(high) NK cells could be converted into CD11b(+)Gr1(+) MDSC ex vivo. Transfer of CD27(high) NK cells from tumor-bearing mice into tumor-bearing recipients was associated with conversion to MDSC in a manner associated with reduced numbers of CD11b(high)CD27(high) and CD11b(high)CD27(low) NK cell populations in the recipients. Our results identify a pathway of MDSC development from immature NK cells in tumor-bearing hosts, providing new insights into how tumor cells modulate their host immune microenvironment to escape immune surveillance.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Células Mieloides/imunologia , Neoplasias/imunologia , Microambiente Tumoral , Animais , Arginase/genética , Arginase/metabolismo , Western Blotting , Antígeno CD11b/genética , Antígeno CD11b/metabolismo , Diferenciação Celular , Proliferação de Células , Citometria de Fluxo , Humanos , Vigilância Imunológica , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Células Mieloides/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Óxido Nítrico/metabolismo , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
A 43-year-old man, who received total gastrectomy five years ago for advanced gastric cancer, underwent a screening colonoscopy and abdominal CT scan. Abdominal CT scan revealed no abnormal findings. Colonoscopy revealed polyps at the rectum, which were removed by polypectomy. The patient did not complain of abdominal pain or discomfort throughout the procedure. But, he developed right upper quadrant abdominal pain on the next day after colonoscopy. Abdominal CT scan revealed the distended gallbladder with mild wall thickening and suspicious sandy stones or sludge in the gallbladder. The patient underwent an open cholecystectomy. Pathology was compatible with acute cholecystitis. We should be aware of and consider cholecystitis in the differential diagnosis for patients with abdominal pain after colonoscopy.