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1.
Rev Iberoam Micol ; 37(2): 41-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041191

RESUMO

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy.


Assuntos
Betacoronavirus , Candidíase Invasiva/epidemiologia , Coinfecção/epidemiologia , Infecções por Coronavirus/epidemiologia , Aspergilose Pulmonar Invasiva/epidemiologia , Pneumonia por Pneumocystis/epidemiologia , Pneumonia Viral/epidemiologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por Coronavirus/sangue , Humanos , Interferon gama/sangue , Interleucinas/sangue , Pandemias , Pneumonia Viral/sangue , Espanha/epidemiologia , Fator de Necrose Tumoral alfa/sangue
2.
Medicine (Baltimore) ; 99(41): e22504, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031288

RESUMO

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Herpes Zoster/epidemiologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Linfócitos T , Idoso , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Interferon gama/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
3.
Cell Mol Immunol ; 17(10): 1092-1094, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32917983
4.
Virus Res ; 289: 198171, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32979474

RESUMO

BACKGROUND: Innate and adaptive immune responses have been evaluated in infected patients with COVID-19. The severity of the disease has been supposed to be associated with some profile not reported with other bacterial and viral pneumonia. We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. METHODS: A prospective cohort with moderate and severe cases of COVID-19 infection from June to July 2020. Blood samples from patients were collected regularly to evaluate IFN-γ, TNF-α, IL-4, IL-6, and IL-10. Clinical, laboratory, radiological data, and outcomes were recorded. The outcome variable was in-hospital death, survival, mechanical ventilation, and admission at the intensive care unit. Data are presented in median and interquartile range [IQR]. RESULTS: We evaluated the Th1 and Th2 responses according to evolution, distinguishing possible predictive markers. The IFN-γ median of 323 pg/mL [IQR 166-570] was found in patients who died and 208 pg/mL [IQR 155-392] in the survival group (p = 0.017). IFN-γ was also higher in the early stages of the disease (394 pg/mL [IQR 229-575] against 162 pg/mL [IQR 117-259], p < 0.001). IL-4 that was increased in late-stage (182 pg/mL [IQR 162-199] against 131 pg/mL [IQR 124-152], p < 0.001) but not associated with mortality. Also, death was also related to male gender (relative risk = 1.5 [95 % confidence interval = 1.1-2.0]). CONCLUSION: Our results suggest that the activation of the host immune response between Th1 or Th2 in COVID-19 infection may be related to the final result between discharge or death. This implies an attempt to control cytokines, such as IFN-γ, with combined therapies for clinical treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Interferon gama/fisiologia , Pandemias , Pneumonia Viral/mortalidade , Idoso , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Citocinas/sangue , Progressão da Doença , Feminino , Mortalidade Hospitalar , Humanos , Imunidade Inata , Pacientes Internados/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Prognóstico , Estudos Prospectivos , Respiração Artificial , Fatores de Risco , Células Th1/imunologia , Células Th2/imunologia
5.
BMC Infect Dis ; 20(1): 553, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736606

RESUMO

BACKGROUND: We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis. METHODS: We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays. RESULTS: Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively. CONCLUSIONS: Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.


Assuntos
Interferon gama/sangue , Interleucina-10/sangue , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Canadá/epidemiologia , Criança , Pré-Escolar , Busca de Comunicante , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose/sangue , Estados Unidos/epidemiologia , Adulto Jovem
6.
Medicine (Baltimore) ; 99(27): e21010, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629720

RESUMO

The net level of immunosuppression in kidney transplant recipients is difficult to assess. QuantiFERON Monitor (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. The aim of our study was to compare QFM testing results in stable kidney transplant recipients and kidney transplant recipients with infection, in a single-centre cohort.We enrolled 71 kidney transplant recipients from our transplantation centre. They were divided into 2 groups according to clinical presentation (Stable kidney transplant recipients or Infection).There were no significant differences in interferon-γ release between the 2 groups (Stable kidney transplant recipients 140.59 ±â€Š215.28 IU/ml, Infection group 78.37 ±â€Š197.03 IU/ml, P = .24). A further analysis revealed that kidney transplant recipients presenting with bacterial infection had significantly lower IFN-γ release when compared to stable kidney transplant recipients (26.52 ±â€Š42.46 IU/ml vs 140.59 ±â€Š215.28 IU/ml, P = .04).Kidney transplant recipients presenting with bacterial infection had lower IFN-γ release when compared to stable kidney transplant recipients. The QFM test may be useful as a tool to help guide immunosuppression dosing in kidney transplant recipients, but further studies are required to confirm its diagnostic value.


Assuntos
Imunossupressão/efeitos adversos , Testes de Liberação de Interferon-gama/métodos , Interferon gama/sangue , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Imunidade Celular/imunologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplantados/estatística & dados numéricos
7.
Immunol Med ; 43(3): 130-134, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32511082

RESUMO

The aim of the work was a comprehensive assessment of the cytokine system and peripheral blood osteocalcin with the establishment of features of their interconnections in children with congenital cleft lip and palate (CCLP) in comparison with corresponding controls at different age periods. Levels of IL17, IL4, IL6, IL1ß, IFNγ and osteocalcin were analyzed by enzyme immunoassay in the peripheral blood of 80 children (0-12 months, 1-3 years, 4-9 years, 10-15 years) with CCLP and age-appropriate control of healthy individuals (40 people). An analysis of the obtained data shows that in children with CCLP we revealed significant differences between pro-inflammatory (IL1ß, IL6, IL17), regulatory (IFNγ), anti-inflammatory (IL4) cytokines and osteocalcin compared with controls. Differences were found in the content of IL17, IFNγ, IL4 and osteocalcin in healthy children and in children with CCLP in postnatal ontogenesis. Cytokine deregulation of immunosteogenesis in CCLP, leading to a significant deficit of osteocalcin in the first year of life due to imbalance of the cytokine profile: discordant IL17, IFNγ and IL4 were detected. Obtained data are undoubtedly important in the future for developing new strategies for targeted therapy aimed at normalizing osteocalcin levels at different age periods in children with CCLP.


Assuntos
Fenda Labial/imunologia , Fissura Palatina/imunologia , Citocinas/sangue , Mediadores da Inflamação/sangue , Osteocalcina/sangue , Osteogênese/imunologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Fenda Labial/sangue , Fenda Labial/fisiopatologia , Fissura Palatina/sangue , Fissura Palatina/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-1beta , Interleucina-4/sangue , Interleucina-6/sangue , Masculino
8.
Exp Parasitol ; 215: 107901, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32525007

RESUMO

Eimeria tenella (E. tenella) has caused severe economic loss in chicken production, especially after the forbidden use of antibiotics in feed. Considering the drug resistant problem caused by misuse of chemoprophylaxis and live oocyst vaccines can affect the productivity of chickens, also it has the risk to reversion of virulence, the development of efficacious, convenient and safe vaccines is still deeply needed. In this study, the EtMic2 protein of E. tenella was anchored on the surface of Lactobacillus plantarum (L. plantarum) NC8 strain. The newly constructed strain was then used to immunize chickens, followed by E. tenella challenge. The results demonstrated that the recombinant strain could provide efficient protection against E. tenella, shown by increased relative body weight gains, percentages of CD4+ and CD8+ T cells, humoral immune response and inflammatory cytokines. In addition, decreased cecum lesion scores and fecal oocyst shedding were also observed during the experiment. In conclusion, this study proves the possibility to use L. plantarum as a vessel to deliver protective antigen to protect chickens against coccidiosis.


Assuntos
Antígeno 12E7/imunologia , Galinhas/parasitologia , Coccidiose/veterinária , Eimeria tenella/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas Protozoárias , Animais , Antígenos de Protozoários/imunologia , Ceco/parasitologia , Coccidiose/economia , Coccidiose/parasitologia , Coccidiose/prevenção & controle , Eimeria tenella/química , Citometria de Fluxo/veterinária , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Imunoglobulina A Secretora/biossíntese , Imunoglobulina G/sangue , Interferon gama/sangue , Interleucina-2/sangue , Intestinos/imunologia , Lactobacillus plantarum/genética , Lactobacillus plantarum/imunologia , Doenças das Aves Domésticas/economia , Doenças das Aves Domésticas/parasitologia , Distribuição Aleatória , Vacinas Sintéticas
9.
Medicine (Baltimore) ; 99(26): e20630, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590737

RESUMO

Previous studies have suggested that the anticancer agent, arsenic trioxide (ATO), could attenuate T cell mediated immunity by not only inhibiting the proliferative response of T cells but by also increasing the frequency of regulatory T cells (Tregs). Furthermore, ATO represents a reasonable salvage treatment in some patients with refractory severe aplastic anemia (SAA). The current study aimed to evaluate the function of ATO on the Tregs percentage and cytokines changes in the peripheral blood mononuclear cells (PBMCs) of SAA patients.PBMCs were collected from 20 newly diagnosed SAA patients in Henan Cancer Hospital and treated with different concentrations of ATO (0, 1, 2.5, and 5 µmol/L). Then we investigated the efficacy of ATO on Tregs ratio and the levels of interferon (IFN)-γ, interleukin (IL)-4, IL-17 and transforming growth factor (TGF)-ß1 in the peripheral blood of SAA patients in vitro.The results showed that ATO significantly increased the proportion of Tregs (P < .001) at 2.5 and 5 µmol/L concentrations, and the proportion of Tregs was increased with increasing ATO concentration (r = 0.524). At 1 (P = .03), 2.5 (P < .001) and 5 µmol/L (P < .001), ATO significantly up-regulated the expression levels of Foxp3 mRNA, which was positively and linearly correlated with the increase of Tregs cell-frequency (r = 0.52, 95%CI, 0.37-0.67). In addition, ATO significantly reduced the levels of IFN-γ (at 1, 2.5 and 5 µmol/L, P < .001), IL-4 (at 2.5 µmol/L, P = .009; at 5 µmol/L, P < .001), and IL-17 (at 2.5, P = .016; at 5 µmol/L, P < .001). ATO significantly reduced the levels of TGF-ß1 at 5 µmol/L (P = .03), but showed no significant effects at 1 and 2.5 µmol/L (P > .05).ATO could mediate the immune regulation, which might contribute to improve hematopoietic recovery in SAA patients.


Assuntos
Anemia Aplástica/sangue , Antineoplásicos/administração & dosagem , Trióxido de Arsênio/administração & dosagem , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/sangue , Anemia Aplástica/tratamento farmacológico , Apoptose/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Macrófagos/metabolismo , RNA Mensageiro/metabolismo , Regulação para Cima
10.
BMC Infect Dis ; 20(1): 258, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234012

RESUMO

BACKGROUND: Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms and Mycobacterium simiae is one of the slowest growing Non-tuberculous mycobacteria. This is the first case report of Mycobacterium simiae infection in Sri Lanka and only very few cases with extrapulmonary manifestation reported in the literature. CASE PRESENTATION: A 24-year-old, previously healthy Sri Lankan male presented with generalized lymphadenopathy with discharging sinuses, evening pyrexia, weight loss, poor appetite and splenomegaly. Lymph node biopsies showed sheets of macrophages packed with organisms in the absence of granulomata. Ziehl Neelsen, Wade Fite and Giemsa stains revealed numerous red coloured acid-fast bacilli within foamy histiocytes. Slit skin smear for leprosy was negative and tuberculosis, fungal and bacterial cultures of the lymph node and bone marrow did not reveal any growth. Later he developed watery diarrhea and colonoscopy revealed multiple small polyps and ulcers throughout the colon extending up to the ileum, Which was confirmed to be due to cytomegalovirus confirmed by PCR and successfully treated with ganciclovir. Positron emission tomography scan guided biopsies of the gut and lymph nodes confirmed presence of mycobacterial spindle cell pseudo-tumours and PCR assays revealed positive HSP65. The culture grew Mycobacterium Simiae. Flow cytometry analysis on patient's blood showed extremely low T and B cell counts and immunofixation revealed low immunoglobulin levels. His condition was later diagnosed as adult onset immunodeficiency due to anti- interferon - gamma autoantibodies. He was initially commenced on empirical anti-TB treatment with atypical mycobacterial coverage. He is currently on a combination of daily clarithromycin, ciprofloxacin, linezolid with monthly 2 g/kg/intravenous immunoglobulin to which, he had a remarkable clinical response with complete resolution of lymphadenopathy and healing of sinuses. CONCLUSIONS: This infection is considered to be restricted to certain geographic areas such as mainly Iran, Cuba, Israel and Arizona and this is the first case report from Sri lanka. Even though the infection is mostly seen in the elderly patients, our patient was only 24 years old. In the literature pulmonary involvement was common presentation, but in this case the patient had generalized lymphadenopathy and colonic involvement without pulmonary involvement.


Assuntos
Síndromes de Imunodeficiência/imunologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/patogenicidade , Autoanticorpos/sangue , Ciprofloxacino/uso terapêutico , Claritromicina/uso terapêutico , Humanos , Biópsia Guiada por Imagem , Interferon gama/sangue , Linfonodos/microbiologia , Linfadenopatia/etiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Tomografia por Emissão de Pósitrons , Sri Lanka , Adulto Jovem
11.
J Clin Neurosci ; 78: 323-326, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32336641

RESUMO

Immune response may play a pivotal role in the pathogenesis of the common synucleinopathy as Parkinson's disease (PD) and could be mediated with the accumulation of neurotoxic alpha-synuclein. There is limited evidence for immune response in another synucleinopathy as dementia with Lewy bodies (DLB). Recent data suggest that immune response may contribute to cognitive impairment. We aimed to estimate plasma cytokine profile in patients with synucleinopathies with dementia (PD dementia (PDD), DLB). Plasma cytokine levels (interferon-gamma (IFN-gamma), interleukin (IL)-4 (IL-4), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1)). were estimated in 16 patients with DLB, 19 patients with PDD, 28 patients with PD without dementia (PD) and 19 individuals without neurological disorders (controls) using Luminex array system. Cognitive status was assessed with the Mini-Mental State Examination (MMSE). TNF-alpha and IL-6 plasma levels were elevated in patients with synucleinopathies with dementia (DLB, PDD) compared to controls and IL-10 plasma level was increased in PDD compared to controls (p < 0.05). IFN-gamma levels were decreased in PD and PDD patients compared to controls (p < 0.001, p = 0.026, respectively) and in PD patients than in DLB patients (p = 0.032). Patients with PD, PDD, and DLB were characterized by increased plasma levels of MCP-1 compared to controls (p < 0.001). At the same time, no differences in TNF-alpha, IL-10, IL-6 plasma levels in PD patients compared to controls were found. Our study demonstrated more pronounced immune response in synucleinopathies associated with dementia compared to PD without demetia.


Assuntos
Citocinas/sangue , Demência/etiologia , Sinucleinopatias/imunologia , Idoso , Idoso de 80 Anos ou mais , Quimiocina CCL2/sangue , Demência/sangue , Demência/imunologia , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Doença por Corpos de Lewy/sangue , Doença por Corpos de Lewy/imunologia , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Doença de Parkinson/imunologia , Sinucleinopatias/sangue , Sinucleinopatias/complicações , Fator de Necrose Tumoral alfa/sangue
12.
Am J Trop Med Hyg ; 102(5): 943-950, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32124729

RESUMO

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.


Assuntos
Citocinas/metabolismo , Dengue/metabolismo , Hemorragia/etiologia , Hepatite Viral Humana/etiologia , Dengue Grave/metabolismo , Adulto , Citocinas/sangue , Dengue/complicações , Dengue/patologia , Feminino , Hemorragia/metabolismo , Hemorragia/virologia , Hepatite Viral Humana/metabolismo , Hepatite Viral Humana/virologia , Humanos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Interleucina-8/sangue , Interleucina-8/metabolismo , Masculino , Estudos Prospectivos , Dengue Grave/complicações , Dengue Grave/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral
13.
PLoS One ; 15(3): e0230261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176735

RESUMO

BACKGROUND: We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA, and germline APOBEC3A/B deletion polymorphism in patients with breast cancers and to investigate the correlation between their expressions and clinicopathological characteristics. METHODS: RNA and DNA samples were extracted from 138 breast cancer tissues and adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using quantitative real-time polymerase chain reaction. Insertion and deletion PCR assays were performed to detect the A3B deletion allele. The serum concentrations of soluble programmed death-ligand 1 (sPD-L1) and interferon gamma were determined using enzyme-linked immunosorbent assays. RESULTS: A3B mRNA expression levels were significantly higher in triple-negative breast cancers compared to hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancers. Older age of the patient and high ki-67 expression were associated with increased expression levels of A3A and A3B mRNA. Advanced tumor stage, presence of lymph node involvement, and high histological grade were associated with increased expression levels of A3A mRNA. The APOBEC3A/B deletion allele was found in 77 (55.8%) patients. TP53 and PIK3CA mutations were detected in 62 (44.9%) and 31 (22.5%) patients, respectively. The presence of a PIK3CA mutation was associated with lower A3A mRNA expression levels. There was a weak positive relationship between A3A mRNA expression levels and serum sPD-L1 levels. CONCLUSIONS: There was a difference in A3B mRNA expression levels according to breast cancer subtypes, and high levels of A3A and A3B mRNA expressions were associated with an aggressive phenotype. There was a high incidence of APOBEC3A/B deletion allele. Further studies are needed to identify the clinical significance of APOBEC in Asian patients with breast cancer.


Assuntos
Neoplasias da Mama/genética , Citidina Desaminase/genética , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Menor/genética , Proteínas/genética , Antígeno B7-H1/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/classificação , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Predisposição Genética para Doença , Humanos , Interferon gama/sangue , Pessoa de Meia-Idade , Polimorfismo Genético , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Deleção de Sequência , Proteína Supressora de Tumor p53/genética
14.
Clin Immunol ; 214: 108383, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32169441

RESUMO

The relationship between microRNA (miR) and immune activity in allergic rhinitis (AR) remains unclear. 37 children with AR and 30 healthy children were enrolled to study the correlation of miR-223 and IL-35. There was a significant inverse correlation between plasma levels of IL-35 and serum eosinophil cationic protein (ECP) levels and eosinophils counts, while there was a positive correlation between serum miR-223 level and ECP levels and eosinophils counts. Besides, the serum levels of IL-35 or miR-223 were found to be negatively or positively correlated with TNSS respectively. The serum level of miR-223 was increased, while IL-35 level was decreased. Moreover, the expression of miRNA-223 was inversely correlated with expression of IL-35. Finally, the levels of miR-223 and IL-35 were related to Th1/Th2 cytokines, eosinophils count as well as the clinical severity. Our study suggests the potential of miR-223 and IL-35 as a molecular target for the treatment of AR.


Assuntos
Citocinas/biossíntese , Interleucinas/sangue , MicroRNAs/sangue , Rinite Alérgica/sangue , Células Th1/metabolismo , Células Th2/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas/sangue , Citocinas/genética , Proteína Catiônica de Eosinófilo/sangue , Eosinófilos , Feminino , Humanos , Lactente , Interferon gama/sangue , Contagem de Leucócitos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Rinite Alérgica/genética , Rinite Alérgica/fisiopatologia
15.
Cancer Res ; 80(9): 1875-1884, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32107212

RESUMO

Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10-78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment. SIGNIFICANCE: Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ligação a DNA/genética , Dasatinibe/uso terapêutico , Linfadenopatia Imunoblástica/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Proteínas Proto-Oncogênicas/genética , Receptores de Antígenos de Linfócitos T/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/genética , Idoso , Animais , Antineoplásicos/administração & dosagem , Dasatinibe/administração & dosagem , Modelos Animais de Doenças , Esquema de Medicação , Feminino , Humanos , Linfadenopatia Imunoblástica/sangue , Linfadenopatia Imunoblástica/genética , Interferon gama/sangue , Interleucinas/sangue , Linfoma de Células T/sangue , Linfoma de Células T/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-vav/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/sangue
16.
Acta Trop ; 205: 105387, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32035053

RESUMO

Dog vaccination is considered an effective way of reducing Leishmania infantum infection incidence in the canine population, as well as its transmission to humans. However, the use of partially effective vaccines can have the detrimental effect of "masking" vaccinated asymptomatic carriers, capable of harbouring the parasite and transmitting it to naïve individuals. After eight years on the European market, few studies have been released on CaniLeish® vaccine safety and efficacy. The present study, a one-year randomized CaniLeish® vaccine field trial, was performed in a canine leishmaniosis endemic area and included animals selected from a native dog population (n = 168). No severe adverse reactions were observed in vaccinated dogs (n = 85). Cases of active L. infantum infection were detected by serological, molecular and clinical follow-up of dogs. One-year post-vaccination, no differences in number or severity of L. infantum active infections were observed between study groups (n = 4 in each group). Vaccine-induced cellular immunity, assessed through interferon-γ quantification, showed significantly higher levels of this cytokine one-month post-vaccination in the vaccine group (p < 0.001), but no differences were observed after nine months between trial groups (p = 0.078). These results fail to support the reported CaniLeish® efficacy in the prevention of active L. infantum infection in dogs from endemic areas and naturally exposed to the parasite.


Assuntos
Doenças do Cão/prevenção & controle , Leishmania infantum/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/veterinária , Vacinação/veterinária , Animais , Doenças do Cão/epidemiologia , Cães , Feminino , Interferon gama/sangue , Vacinas contra Leishmaniose/efeitos adversos , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Masculino
17.
Artigo em Chinês | MEDLINE | ID: mdl-31954387

RESUMO

Objective: To investigate the effect of isosorbide mononitrate (ISMN) targeted nanoparticles on inflammatory factors of sinusitis by establishing a rabbit model of rhinosinusitis. Methods: Thirty healthy rabbits, male and female, weighing 2.5-3.5 kg, were randomly divided into 6 groups with 5 rabbits in each group. Group A was the control group. The model of rabbit sinusitis was established in group B to F, and CT was used to confirm the model was successful. After placing tubes into the maxillary sinus in the group C to F, saline, 45 mg/ml ISMN, 45 mg/ml ISMN nanoparticles and 45 mg/ml ISMN targeted nanoparticles were used to wash the maxillary sinus, respectively. Blood samples were collected from the ear vein of rabbits on day 7, 14, 21, 28, 35 and 42 after modeling respectively. Changes in the expression levels of inflammatory factors in rabbits during the modeling process and after drug washing were detected by ELISA. After the drug intervention, the maxillary sinus mucosa was taken for real-time quantitative PCR to detect the changes in the mRNA level of inflammatory factors. SPSS 22.0 software was used to process the data. Results: Rabbit model of sinusitis was successfully established. ELISA showed that after the action of ISMN targeted nanoparticles of 1 week (42th day after modeling), the levels of (interleukin, IL) 4, IL-8, IL-17A and interferon γ (IFN-γ) in the blood were lower compared with that of 35th day after modeling, the difference was statistically significant (5.57±1.20 vs 19.73±0.68, 66.41±11.87 vs 154.68±13.13, 17.96±1.87 vs 28.23±0.80, 53.56±5.66 vs 111.93±7.29, all P<0.05). Compared with the ISMN nanoparticles and ISMN, the ISMN targeted nanoparticles reduced the levels of IL-4, IL-8, IL-17A and IFN-γ more obviously, the differences were statistically significant (13.26±1.43 vs 8.81±1.33 vs 7.14±2.16, 89.47±17.80 vs 41.07±7.77 vs 15.84±3.72, 10.28±2.07 vs 3.06±1.62 vs 1.82±0.90, 62.16±6.18 vs 35.12±4.62 vs 27.89±10.18, all P<0.05). Real-Time PCR showed that after the flushing of ISMN targeted nanoparticles, the levels of IL-4, IL-8, IL-17A and IFN-γ mRNA were lowest compared with that of the model group, ISMN nanoparticles and ISMN group. Conclusion: ISMN targeted nanoparticles can reduce the level of inflammatory factors in rabbit sinusitis model.


Assuntos
Dinitrato de Isossorbida/uso terapêutico , Nanopartículas/uso terapêutico , Sinusite/sangue , Sinusite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Interleucina-8/sangue , Masculino , Coelhos , Distribuição Aleatória
18.
PLoS One ; 15(1): e0227636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917802

RESUMO

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.


Assuntos
Moléculas de Adesão Celular/sangue , Interferon gama/sangue , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pneumonia Bacteriana/sangue , Tuberculose Pulmonar/sangue , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico
19.
Cancer Sci ; 111(4): 1314-1323, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31971321

RESUMO

Adult patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T-cell engager (BiTE) immuno-oncology therapy with dual specificity for CD19 and CD3 that redirects patients' CD3-positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open-label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B-precursor ALL. Patients received 9 µg/day blinatumomab during week 1 and 28 µg/day during weeks 2-4, with a 2-week treatment-free interval (6-week cycle); patients received 28 µg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose-limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5-6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Linfoma de Células B/tratamento farmacológico , Neoplasia Residual/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Idoso , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/sangue , Anticorpos Biespecíficos/farmacocinética , Antígenos CD19/genética , Antígenos CD19/imunologia , Linfócitos B/patologia , Complexo CD3/genética , Complexo CD3/imunologia , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Interferon gama/sangue , Estimativa de Kaplan-Meier , Linfoma de Células B/sangue , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/sangue , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Indução de Remissão , Linfócitos T/imunologia
20.
Clin Sci (Lond) ; 134(2): 207-223, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31934722

RESUMO

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapy for blood cancers; but results in the development of graft-versus-host disease (GVHD) in up to 70% of recipients. During GVHD, tissue damage results in ATP release into the extracellular compartment activating P2X7 on antigen-presenting cells, leading to the release of pro-inflammatory cytokines and subsequent activation of donor T cells. Therefore, the aim of the present study was to examine murine (m) P2rx7 and human (h) P2RX7 gene expression in GVHD target organs of humanised mice, and further characterise disease impact in these organs. METHODS: NOD-scid IL2Rγnull (NSG) mice were injected with human peripheral blood mononuclear cells (hu-PBMC-NSG mice) or phosphate-buffered saline (PBS, control). Leucocytes were assessed by flow cytometry; gene expression was measured by quantitative polymerase chain reaction (qPCR), and tissue sections examined by histology. RESULTS: Compared with control mice, hu-PBMC-NSG mice had increased mP2rx7 and mP2rx4 expression in the duodenum, ileum and skin. hP2RX7 was expressed in all tissues examined. hu-PBMC-NSG mice also displayed increased mReg3g expression in the duodenum and ileum, despite limited histological gut GVHD. hu-PBMC-NSG mice showed histological evidence of GVHD in the skin, liver and lung. Compared with control mice, hu-PBMC-NSG mice displayed increased ear swelling. CONCLUSION: Combined data revealed that P2rx7 is up-regulated in gut and skin GVHD and that P2RX7 is present in target tissues of GVHD, corresponding to human leucocyte infiltration. Data also reveal increased mReg3g expression and ear swelling in hu-PBMC-NSG mice, offering new measurements of early-stage gut GVHD and skin GVHD, respectively.


Assuntos
Trato Gastrointestinal/metabolismo , Doença Enxerto-Hospedeiro/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Pele/metabolismo , Adulto , Animais , Antígenos CD/metabolismo , Modelos Animais de Doenças , Orelha/patologia , Feminino , Doença Enxerto-Hospedeiro/sangue , Humanos , Interferon gama/sangue , Leucócitos Mononucleares/metabolismo , Fígado/patologia , Pulmão/patologia , Masculino , Camundongos , Proteínas Associadas a Pancreatite/metabolismo , Baço/imunologia , Linfócitos T/imunologia , Regulação para Cima/genética , Adulto Jovem
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