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1.
Immunol Res ; 69(6): 576-583, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34417958

RESUMO

The development of vaccines to prevent SARS-CoV-2 infection has mainly relied on the induction of neutralizing antibodies (nAbs) to the Spike protein of SARS-CoV-2, but there is growing evidence that T cell immune response can contribute to protection as well. In this study, an anti-receptor binding domain (RBD) antibody assay and an INFγ-release assay (IGRA) were used to detect humoral and cellular responses to the Pfizer-BioNTech BNT162b2 vaccine in three separate cohorts of COVID-19-naïve patients: 108 healthcare workers (HCWs), 15 elderly people, and 5 autoimmune patients treated with immunosuppressive agents. After the second dose of vaccine, the mean values of anti-RBD antibodies (Abs) and INFγ were 123.33 U/mL (range 27.55-464) and 1513 mIU/mL (range 145-2500) in HCWs and 210.7 U/mL (range 3-500) and 1167 mIU/mL (range 83-2500) in elderly people. No correlations between age and immune status were observed. On the contrary, a weak but significant positive correlation was found between INFγ and anti-RBD Abs values (rho = 0.354, p = 0.003). As to the autoimmune cohort, anti-RBD Abs were not detected in the two patients with absent peripheral CD19+B cells, despite high INFγ levels being observed in all 5 patients after vaccination. Even though the clinical relevance of T cell response has not yet been established as a correlate of vaccine-induced protection, IGRA testing has showed optimal sensitivity and specificity to define vaccine responders, even in patients lacking a cognate antibody response to the vaccine.


Assuntos
Vacinas contra COVID-19/imunologia , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Hospedeiro Imunocomprometido/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Vacina BNT162 , COVID-19/imunologia , COVID-19/prevenção & controle , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Imunogenicidade da Vacina/imunologia , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Interferon gama/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Domínios Proteicos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Vacinação , Adulto Jovem
2.
Dis Markers ; 2020: 1318930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33110454

RESUMO

OBJECTIVES: We investigated the influence of pain decrease after lumbar microdiscectomy on the interferon gamma (IFN-γ) serum level in patients with lumbar disc herniations. The study challenges the mechanism of sciatica pain and the role of IFN-γ in radicular pain development. Material and Methods. We performed clinical and immunoenzymatic assessment in a group of 27 patients with lumbar radicular pain due to disc herniations before and 3 months after surgery. Clinical status was assessed with the use of the Numeric Rating Scale (NRS), the Pain Rating Index and Pain Intensity Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN-γ were ascertained by an immunoenzymatic method. RESULTS: We observe significant correlations between the results of the pain in the back region assessment NRS back scale after the surgery with the level of IFN-γ before the procedure (r s = 0.528; p = 0.008) and after the procedure (r s = 0.455; p = 0.025). These are moderate and positive correlations-the decrease in pain is correlated with the lower IFN-γ level. Additionally, there are significant correlations between the results of the PRI scale and the IFN-γ level. The PRI score before surgery correlates positively with IFN-γ after surgery (r s = 0.462; p = 0.023), and the PRI score after surgery correlates positively with IFN before surgery (r s = 0.529; p = 0.005) and after surgery (r s = 0.549; p = 0.003). All correlations are moderate in severity-severe pain before surgery correlates with a higher level of IFN-γ after surgery and also higher IFN-γ before surgery. There were significant differences in the IFN-γ level before (Z = -2.733; p = 0.006) and after (Z = -2.391; p = 0.017) surgery in the groups of patients with and without nerve compression. In the group of patients with nerve compression, the level of IFN-γ before and after surgery was lower. CONCLUSIONS: Less pain ratio after operation correlates with the level of IFN-γ. In the group of patients without significant nerve compression confirmed by MRI scans, the level of IFN-γ before and after surgery was higher than that in the group with nerve root compression.


Assuntos
Interferon gama/sangue , Deslocamento do Disco Intervertebral/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Dor Pós-Operatória/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/diagnóstico por imagem , Medição da Dor , Dor Pós-Operatória/etiologia , Estudos Prospectivos
3.
Int Immunol ; 32(12): 799-804, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-32645711

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a member of the beta-coronavirus genus of zoonotic origin that emerged in the Arabian Peninsula and is associated with significant morbidity and mortality. This study was conducted to assess the plasma levels of cytokines to evaluate the Th1/Th2 status among 46 MERS-CoV-infected patients (19 asymptomatic and 27 symptomatic) and 52 normal healthy controls using a customized luminex kit. Comparative analysis of data between MERS-CoV-infected patients and normal healthy controls revealed that although no difference was observed between asymptomatic MERS-CoV patients and controls, the mean plasma levels of interleukin (IL)-10 (44.69 ± 40.04 pg ml-1 versus 14.84 ± 6.96 pg ml-1; P < 0.0001), IL-4 (22.46 ± 8.02 pg ml-1 versus 16.01 ± 9.97 pg ml-1; P < 0.0001), IL-5 (10.78 ± 2.86 pg ml-1 versus 8.06 ± 1.41 pg ml-1; P < 0.0001) and IL-13 (14.51 ± 3.97 pg ml-1 versus 11.53 ± 4.16 pg ml-1; P < 0.003) in MERS-CoV symptomatic patients were significantly higher than the normal controls. The mean plasma levels of interferon (IFN)-γ and IL-12 were no different among the study groups. The cytokine profile among symptomatic MERS-CoV-infected patients was skewed to a Th2 type immune response.


Assuntos
Infecções por Coronavirus/imunologia , Citocinas/sangue , Coronavírus da Síndrome Respiratória do Oriente Médio , Células Th1/imunologia , Células Th2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-12/sangue , Interleucina-13/sangue , Interleucina-4/sangue , Interleucina-5/sangue , Masculino , Pessoa de Meia-Idade
4.
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
5.
Front Immunol ; 11: 963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508837

RESUMO

The majority of data on human Natural Killer (NK) cell phenotype and function has been generated using cryopreserved peripheral blood mononuclear cells (PBMCs). However, cryopreservation can have adverse effects on PBMCs. In contrast, investigating immune cells in whole blood can reduce the time, volume of blood required, and potential artefacts associated with manipulation of the cells. Whole blood collected from healthy donors and cancer patients was processed by three separate protocols that can be used independently or in parallel to assess extracellular receptors, intracellular signaling protein phosphorylation, and intracellular and extracellular cytokine production in human NK cells. To assess extracellular receptor expression, 200 µL of whole blood was incubated with an extracellular staining (ECS) mix and cells were subsequently fixed and RBCs lysed prior to analysis. The phosphorylation status of signaling proteins was assessed in 500 µL of whole blood following co-incubation with interleukin (IL)-2/12 and an ECS mix for 20 min prior to cell fixation, RBC lysis, and subsequent permeabilization for staining with an intracellular staining (ICS) mix. Cytokine production (IFNγ) was similarly assessed by incubating 1 mL of whole blood with PMA-ionomycin or IL-2/12 prior to incubation with ECS and subsequent ICS antibodies. In addition, plasma was collected from stimulated samples prior to ECS for quantification of secreted IFNγ by ELISA. Results were consistent, despite inherent inter-patient variability. Although we did not investigate an exhaustive list of targets, this approach enabled quantification of representative ECS surface markers including activating (NKG2D and DNAM-1) and inhibitory (NKG2A, PD-1, TIGIT, and TIM-3) receptors, cytokine receptors (CD25, CD122, CD132, and CD212) and ICS markers associated with NK cell activation following stimulation, including signaling protein phosphorylation (p-STAT4, p-STAT5, p-p38 MAPK, p-S6) and IFNγ in both healthy donors and cancer patients. In addition, we compared extracellular receptor expression using whole blood vs. cryopreserved PBMCs and observed a significant difference in the expression of almost all receptors. The methods presented permit a relatively rapid parallel assessment of immune cell receptor expression, signaling protein activity, and cytokine production in a minimal volume of whole blood from both healthy donors and cancer patients.


Assuntos
Citometria de Fluxo , Imunofenotipagem , Interferon gama/sangue , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Células Matadoras Naturais/metabolismo , Neoplasias/sangue , Receptores Imunológicos/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Criopreservação , Estudos de Viabilidade , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Fenótipo , Fosforilação , Estudo de Prova de Conceito , Fluxo de Trabalho
7.
Respir Med ; 152: 89-96, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31128616

RESUMO

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation. CXCL11 has been reported to have unique functional properties in modulating adaptive immunity in model systems so our goal was to examine serum levels of CXCL11 in relation to clinical outcomes in a heterogeneous cohort of sarcoidosis subjects. METHODS: CXCL19, CXCL10, and CXCL11 serum levels were measured in sarcoidosis and healthy subjects using ELISA assay. We determined relationships between CXCL11 and standard clinical inflammatory markers, expression of IFN-γ-related genes in whole blood, organ involvement, dyspnea scores, and measures of pulmonary function. RESULTS: In a cross-sectional analysis of 104 sarcoidosis subjects, serum CXCL11 was significantly elevated compared to 49 healthy controls (p < 0.001). CXCL11 was positively correlated with CXCL9 and CXCL10 (p < 0.001), sedimentation rate (p < 0.01), and mean expression of three IFN-γ-related genes in whole blood (GBP1, STAT1, and STAT2) (p < 0.001). CXCL11 was inversely correlated with FVC %predicted (%pred) and FEV1 %pred and higher levels were associated with higher patient-reported dyspnea scores. We found positive correlations between CXCL11 and number of organs involved. Using survival analyses, we found that CXCL11 levels were predictive of future pulmonary function test (PFT) decline (log rank <0.001 and HR of log10(CXCL11) = 5.1, 95% CI 1.2-21, p = 0.026). CONCLUSIONS: The pattern of expression of serum CXCL11 in sarcoidosis patients suggests that this blood measure could be helpful in identifying patients that need longer-term monitoring for progressive thoracic and extra-thoracic sarcoidosis.


Assuntos
Quimiocina CXCL10/sangue , Quimiocina CXCL11/sangue , Quimiocina CXCL9/sangue , Sarcoidose/metabolismo , Adulto , Biomarcadores/metabolismo , Efeitos Psicossociais da Doença , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Interferon gama/sangue , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Testes de Função Respiratória/métodos , Sarcoidose/mortalidade , Sarcoidose/patologia , Sarcoidose/fisiopatologia , Análise de Sobrevida
8.
Indian J Pathol Microbiol ; 61(1): 76-80, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29567888

RESUMO

BACKGROUND: Scrub typhus is lesser known cause of fever of unknown origin in India. Even if there have been reports documenting the prevalence of scrub typhus in different parts of India, it is still an unknown entity, and clinicians usually do not consider it as differential diagnosis. The present study was performed to document the prevalence of scrub typhus among febrile patients in western part of Uttar Pradesh and to assess the clinical profile of infected patients on the one hand and knowledge, attitude, and practices among clinicians on the other. MATERIALS AND METHODS: A total of 357 adult patients with fever of more than 5-day duration were recruited. All patients underwent complete physical examination, and detailed clinical history was elicited as per predesigned pro forma. After primary screening to rule out malaria, enteric fever, and leptospirosis infection, secondary screening for scrub typhus was done by rapid screen test and IgM ELISA. RESULTS: Scrub typhus infection was positive in 91 (25.5%) cases. The most common symptoms among the patients were fever (100%), pain in abdomen (79.1%), pedal edema 56 (61.5%), rash 44 (48.3%), headache 44 (48.3%), vomiting 42 (46.1%), constipation 33 (36.2%), cough 28 (30.7%), and lymphadenopathy 20 (21.9%). The median values of interleukin-8, interferon-gamma, and tumor necrosis factor-alpha in healthy controls were 15.54 pg/ml, 7.77 pg/ml, and 54.1 pg/ml, respectively, while the median values of these cytokines in scrub typhus-positive patients were 21.04 pg/ml, 8.74 pg/ml, and 73.8 pg/ml, respectively. CONCLUSION: Our results highlight that scrub typhus infection is an important cause of pyrexia of unknown origin, and active surveillance is necessary to assess the exact magnitude and distribution of the disease.


Assuntos
Febre/imunologia , Interferon gama/sangue , Interleucina-8/sangue , Tifo por Ácaros/epidemiologia , Tifo por Ácaros/imunologia , Fator de Necrose Tumoral alfa/sangue , Adulto , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/epidemiologia , Febre/etiologia , Febre de Causa Desconhecida/diagnóstico , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/imunologia , Febre de Causa Desconhecida/parasitologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Orientia tsutsugamushi/imunologia , Orientia tsutsugamushi/isolamento & purificação , Médicos/psicologia , Médicos/estatística & dados numéricos , Prevalência , Tifo por Ácaros/sangue , Tifo por Ácaros/diagnóstico
9.
Microb Pathog ; 108: 114-121, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28487230

RESUMO

Bovine tuberculosis (bTB) is usually diagnosed in vivo and ex vivo on the basis of delayed hypersensitivity reactions with a complex pool of antigens named bovine tuberculin (PPDB). The IFN-γ release assay (IGRA) for bTB is a blood-based assay that improves detection of infected cattle at early stages that escape skin testing. Improvements to IFN-γ testing with specific proteins have been performed to increase sensitivity. DosR regulon-related antigens are well known mycobacterial proteins expressed during the non-replicative phases of infection, this has been useful to improve the diagnosis of subclinical forms of TB in suspected individuals. Transcripts of DosR genes mb2054c, mb2057c, and mb2660c have been identified by our group in lymph nodes of IFN-γ test negative cattle. This led us to hypothesize that DosR-related proteins may potentiate the IFN-γ response to PPDB in animals with a false negative IFN-γ test, making evident subclinical infection. Three hundred animals were evaluated by means of IGRA and post-mortem microbiological analysis of tissue samples to validate M. bovis infection. We found that 176 out of 300 animals showed an overall increased OD in complemented IGRA with two purified protein cocktails in comparison to PPDB alone, and were scrutinized for a subclinical infection; thirty percent when PPDB was supplemented with a cocktail of four DosR antigens, and 70% when PPDB was supplemented with a cocktail of six antigens (four DosR and two RD1 antigens). Forty five animals showed a substantial IFN-γ overproduction but remained negative, and 40 animals changed the result to a positive test. Only 18 out of 176 IFN-γ high producing animals were also positive to M. bovis isolation. Fifty seven animals with no visible lesions at slaughter and with a negative IGRA test result contained M. bovis DNA in tissue samples. In conclusion, Mb1762c, Mb2054c, Mb2057c, and Mb2660c have the potential to increase sensitivity of the IFN-γ in vitro test for bTB diagnosis when supplemented to PPDB.


Assuntos
Infecções Assintomáticas , Testes de Liberação de Interferon-gama/métodos , Testes de Liberação de Interferon-gama/veterinária , Mycobacterium bovis/imunologia , Tuberculina/imunologia , Tuberculose Bovina/diagnóstico , Tuberculose Bovina/imunologia , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Bovinos , DNA Bacteriano , Diagnóstico Diferencial , Interferon gama/sangue , Interferon gama/metabolismo , Linfonodos/imunologia , México , Mycobacterium bovis/genética , Mycobacterium bovis/isolamento & purificação , Proteínas Recombinantes , Regulon , Sensibilidade e Especificidade , Tuberculose Bovina/microbiologia
10.
J Infect ; 71(5): 526-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26253021

RESUMO

UNLABELLED: There are still no reliable tests to distinguish active tuberculosis (TB) from latent TB infection (LTBI). Assessment of CD27 modulation on CD4⁺ T-cells has been suggested as a tool to diagnose different TB stages. OBJECTIVES: To use several cytometric approaches to evaluate CD27 expression on Mycobacterium tuberculosis (Mtb)-specific CD4⁺ T-cells to differentiate TB stages. METHODS: 55 HIV-uninfected subjects were enrolled: 13 active TB; 12 cured TB; 30 LTBI. Whole blood was stimulated with RD1-proteins or Cytomegalovirus-lysate (CMV). Interferon (IFN)-γ response was evaluated by cytometry. The proportion of CD27(±) within the IFN-γ⁺ CD4⁺ T-cells or RATIO of the CD27-median fluorescence intensity (MFI) of CD4⁺ T-cells over the CD27 MFI of IFN-γ⁺ CD4⁺ T-cells was evaluated. RESULTS: The greatest diagnostic accuracy in discriminating active TB vs. LTBI or cured TB was reached by evaluating the CD27(+) CD45RA(-) cells within the IFN-γ⁺ CD4⁺ T-cell subset (76.92 sensitivity for both, and 90% and 91.67% specificity, respectively), although the use of the CD27 MFI RATIO allows for stricter data analysis, independent of the operator. CONCLUSIONS: the study of CD27 expression using different approaches, whether it involves evaluation of CD45RA expression or not, is a robust biomarker for discriminating TB stages.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Tuberculose Latente/diagnóstico , Tuberculose/diagnóstico , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Adulto , Antígenos de Bactérias/imunologia , Biomarcadores , Feminino , Citometria de Fluxo , Humanos , Interferon gama/sangue , Tuberculose Latente/imunologia , Antígenos Comuns de Leucócito/análise , Antígenos Comuns de Leucócito/genética , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Sensibilidade e Especificidade , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Adulto Jovem
11.
Psychiatry Res ; 228(3): 386-92, 2015 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-26160203

RESUMO

We aimed to assess the relationship between cytokine levels and the severity of the manic period in medication free patients. 30 Medication free patients and 28 healthy subjects (HS) were recruited. Plasma levels of pro-inflammatory, anti-inflammatory, inflammatory cytokines, and hs-CRP levels were investigated upon hospital admission, after six weeks follow up in bipolar disease manic episode and the results were compared to HS. The severity of the manic episodes was assessed according to the Young mania rating scale. TNF-α, INF-γ, IL-6 and hs-CRP levels were significantly higher in patients with manic episode of bipolar I disorder before treatment than HS. After treatment the levels of TNF-α, INF-γ, IL-6 and hs-CRP were observed to be significantly decreased. There was no difference between the levels of anti-inflammatory cytokines in patients before or after treatment of bipolar disorder and HS. hs-CRP was observed to be the only parameter correlated with clinical response. The most significant outcome of this study is the correlation between clinical outcome and hs-CRP levels in treatment naive manic episode bipolar type I patients. hs-CRP is the most consistent indicator according to pro-inflammatory, inflammatory and anti-inflammatory cytokines, in predicting treatment outcomes.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Proteína C-Reativa/metabolismo , Citocinas/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama/sangue , Interleucina-6/sangue , Masculino , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
12.
Mem Inst Oswaldo Cruz ; 109(6): 722-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25317700

RESUMO

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3⁺ cells, helper CD4⁺ cells and CD19⁺ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3⁺ and CD4⁺ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.


Assuntos
Anticorpos Antivirais/sangue , Coinfecção/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Hepatite C Crônica/imunologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença Crônica , Coinfecção/virologia , DNA Viral/isolamento & purificação , Egito , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Epstein-Barr/complicações , Feminino , Citometria de Fluxo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C Crônica/complicações , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Interferon gama/sangue , Interleucina-15/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Adulto Jovem
13.
Mem. Inst. Oswaldo Cruz ; 109(6): 722-727, 09/09/2014. graf
Artigo em Inglês | LILACS | ID: lil-723993

RESUMO

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.


Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antivirais/sangue , Coinfecção/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Hepatite C Crônica/imunologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença Crônica , Coinfecção/virologia , DNA Viral/isolamento & purificação , Egito , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Epstein-Barr/complicações , Citometria de Fluxo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C Crônica/complicações , /genética , /imunologia , Interferon gama/sangue , /sangue , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação
14.
PLoS One ; 9(3): e89928, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24657960

RESUMO

Hormone levels shift the immune state in HIV-uninfected pregnant and breastfeeding women away from Th1 responses and toward regulation to permit fetal tolerance. Limited data exist on inflammation during pregnancy or postpartum in HIV-infected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-γ, IL-6, IL-10 and TNF-α at 34 weeks gestation and six months postpartum in HIV-infected women from the Botswana Mashi PMTCT trial who were randomized to breastfeeding or formula-feeding. Differences in inflammatory markers between gestation and postpartum periods, and by randomized feeding method, were estimated using generalized estimating equations, adjusting for baseline plasma HIV-1 viral load, CD4 count, calendar time, and antiretroviral treatment status. Additionally, we studied the association between marker concentrations at six months postpartum and major adverse clinical events over the following 4.5 years, using case-cohort sampling and adjusted Cox proportional hazards models. In 86 breastfeeding and 75 formula-feeding women, hsCRP and D-dimer decreased significantly between 34 weeks gestation and six months postpartum, while IFN-γ increased. There was no significant association between inflammatory marker change and randomized feeding method after adjusting for multiple comparisons and removing outliers. In univariate analysis, TNF-α, D-dimer, and IFN-γ concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-α remained significant in multivariate analysis (HR = 4.16, p = 0.001). In young HIV-infected women in Botswana inflammatory marker concentrations did not differ significantly between women who breast- vs. formula-fed. However, postpartum TNF-α level was predictive of subsequent adverse clinical event.


Assuntos
Aleitamento Materno , Infecções por HIV/imunologia , Antirretrovirais/uso terapêutico , Botsuana , Contagem de Linfócito CD4 , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Humanos , Fórmulas Infantis , Recém-Nascido , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Análise Multivariada , Período Periparto , Período Pós-Parto , Gravidez , Prognóstico , Fator de Necrose Tumoral alfa/sangue , Carga Viral
15.
Toxicol Pathol ; 42(1): 286-92, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24190913

RESUMO

To assess relative sensitivity for detection of cytokines and chemokines in cynomolgus serum samples, we tested three commercially available multiplex array kits using the Luminex® platform with sera from animals exposed by intravenous injection to 150 µg/kg staphylococcal enterotoxin B (SEB) or 20 µg/kg lipopolysaccharide (LPS). Each of these kits detected similar patterns of changes in circulating cytokines/chemokines in response to SEB or LPS stimulation, especially the induction of high amounts of interleukin (IL)-2 and interferon-gamma (IFN-γ) in response to SEB but not LPS. However, there were clear differences in sensitivity for particular analytes, especially for IL-10. Additional experiments that focused on one multiplex array kit demonstrated very low or undetectable levels of cytokines in naive cynomolgus macaques, except for highly variable background levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß. Therefore, multiplex array analysis of circulating cytokine/chemokine patterns was capable of detection of systemic activation of diverse immune cell subsets.


Assuntos
Quimiocina CCL2/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-2/sangue , Interleucina-8/sangue , Análise Serial de Proteínas/métodos , Administração Intravenosa , Animais , Quimiocina CCL4/sangue , Enterotoxinas/administração & dosagem , Enterotoxinas/efeitos adversos , Feminino , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Macaca fascicularis/imunologia , Masculino , Kit de Reagentes para Diagnóstico
16.
Oncol Nurs Forum ; 40(5): 490-500, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23975184

RESUMO

PURPOSE/OBJECTIVES: To examine racial differences in inflammatory cytokine levels (interleukin [IL]-6 and interferon-gamma [IFN-γ]) and breast cancer (BC) risk factors between healthy Caucasian and African American women; to examine differences in relationships of inflammatory cytokine levels with BC risk factors between these groups of women; and to determine the independent contribution of race to IL-6 and IFN-γ after controlling for relevant covariates. DESIGN: Cross-sectional and correlational descriptive design. SETTING: Community surrounding a state university health system in the southeastern United States. SAMPLE: 113 healthy women (65 Caucasians and 48 African Americans) aged 20 years or older and not pregnant. METHODS: Secondary analysis of data collected from self-report questionnaires and blood samples. MAIN RESEARCH VARIABLES: Inflammatory cytokine levels, BC risk factors (age, age at menarche, age at first live birth, family history of BC, breast biopsy, breastfeeding history and duration, body mass index, and physical activity), and race. FINDINGS: Significant racial differences were noted in IL-6 and IFN-γ levels, reproductive or hormonal and lifestyle BC risk factors, and relationships between African American and Caucasian women. Controlling for all other effects, race appeared to be a significant predictor for IL-6 and IFN-γ. CONCLUSIONS: Racial differences in inflammatory cytokines and BC risk factors may provide partial evidence for existing racial disparities in BC for African American and Caucasian women. Additional studies are needed to confirm that potential. IMPLICATIONS FOR NURSING: Additional biobehavioral research in racial disparities in BC may help to inform nurses to target race-specific modifications of lifestyle and behavioral factors to reduce BC health disparity between African American and Caucasian women. KNOWLEDGE TRANSLATION: Being an African American woman predicted a higher level of inflammatory cytokine production after controlling for selected BC risk factors. Great potential exists for inflammatory responses as one of the underlying biologic mechanisms for existing BC disparity and for culturally tailored lifestyle or behavioral modification interventions for reducing BC risk and racial disparity.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Inflamação/etnologia , Interferon gama/sangue , Interleucina-6/sangue , População Branca/estatística & dados numéricos , Adulto , Idoso , Biópsia/estatística & dados numéricos , Mama/patologia , Neoplasias da Mama/prevenção & controle , Estudos Transversais , Saúde da Família , Feminino , Disparidades nos Níveis de Saúde , Humanos , Inflamação/sangue , Inflamação/enfermagem , Lactação , Pessoa de Meia-Idade , História Reprodutiva , Fatores de Risco , Estudos de Amostragem , Autorrelato , Fatores Socioeconômicos , Estresse Psicológico/etnologia , Adulto Jovem
17.
Analyst ; 138(9): 2620-3, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23478509

RESUMO

Interferons (IFNs) play a role in inhibition of tumor growth and participate in immunoreactions. Among IFNs, interferon-γ (IFNγ) is one of the most important therapeutic proteins and its immunodulation ability is better than that of other types. The objective of this study is to develop a manual self-assembled colloidal gold nanoparticle-immunochromatographic strip for human IFNγ using anti-human IFNγ polyclonal and monoclonal antibodies. Colloidal gold with a 25 nm diameter was made from chloroauric acid (HAuCl4), and labeled on anti-IFNγ mAbs as a chrominance reagent. A good linear relationship existed between the pixel intensity and the human IFNγ concentrations from 10-1000 ng mL(-1) in mouse serum and buffer, respectively, the regression equation was Y = 0.159logX + 0.0648, R(2) = 0.992 in mouse serum; Y = 0.294logX + 0.091, R(2) = 0.9969 in phosphate buffer by this proposed strip. Moreover, in the determination for mouse serum samples no cross-reaction occurred and the detection time was approximately 10 minutes. The shelf life of the strip was above 28 days at room temperature. The major advantages of the manual operation model were no expensive instruments and less reagents required. This proposed strip was highly specific, economic, convenient, and no machine was needed in clinical diagnosis.


Assuntos
Cromatografia de Afinidade/instrumentação , Coloide de Ouro/química , Interferon gama/sangue , Fitas Reagentes/análise , Animais , Anticorpos Imobilizados/química , Cromatografia de Afinidade/economia , Humanos , Interferon gama/análise , Limite de Detecção , Camundongos , Camundongos Endogâmicos BALB C , Fitas Reagentes/economia , Fatores de Tempo
18.
Am J Kidney Dis ; 61(1): 22-32, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22784996

RESUMO

BACKGROUND: Guidelines differ on screening recommendations for latent tuberculosis infection (LTBI) prior to immunosuppressive therapy. We aimed to determine the most cost-effective LTBI screening strategy before long-term steroid therapy in a child with new-onset idiopathic nephrotic syndrome. STUDY DESIGN: Markov state-transition model. SETTING & POPULATION: 5-year-old boy with new-onset idiopathic nephrotic syndrome. MODEL, PERSPECTIVE, & TIMEFRAME: The Markov model took a societal perspective over a lifetime horizon. INTERVENTION: 3 strategies were compared: universal tuberculin skin testing (TST), targeted screening using a risk-factor questionnaire, and no screening. A secondary model included the newer interferon γ release assays (IGRAs), requiring only one visit and having greater specificity than TST. OUTCOMES: Marginal cost-effectiveness ratios (2010 US dollars) with effectiveness measured as quality-adjusted life-years (QALYs). RESULTS: At an LTBI prevalence of 1.1% (the average US childhood prevalence in our base case), a no-screening strategy dominated ($2,201; 29.3356 QALYs) targeted screening ($2,218; 29.3356 QALYs) and universal TST ($2,481; 29.3347 QALYs). At a prevalence >10.3%, targeted screening with a risk-factor questionnaire was the most cost-effective option. Higher than a prevalence of 58.5%, universal TST was preferred. In the secondary model, targeted screening with a questionnaire followed by IGRA testing was cost-effective compared with no screening in the base case when the LTBI prevalence was >4.9%. LIMITATIONS: There is no established gold standard for the diagnosis of LTBI. Results of any modeling task are limited by the accuracy of available data. CONCLUSIONS: Prior to starting steroid therapy, only patients in areas with a high prevalence of LTBI will benefit from universal TST. As more evidence becomes available about the use of IGRA testing in children, the assay may become a component of cost-effective screening protocols in populations with a higher burden of LTBI.


Assuntos
Tuberculose Latente/diagnóstico , Cadeias de Markov , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Síndrome Nefrótica/tratamento farmacológico , Esteroides/uso terapêutico , Pré-Escolar , Análise Custo-Benefício , Humanos , Interferon gama/sangue , Tuberculose Latente/sangue , Tuberculose Latente/epidemiologia , Masculino , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários/economia , Teste Tuberculínico/economia
19.
Am J Trop Med Hyg ; 87(1): 70-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22764294

RESUMO

Patients who recover from leishmaniasis usually show development of strong immunity and induction of interferon-γ (IFN-γ) and delayed type hypersensitivity. In a randomized trial, we analyzed the IFN-γ response by using a Quantiferon-Leishmania assay against three Leishmania peptide antigens and compared it with results of the leishmanin skin test (LST) in persons residing in areas in Iran to which zoonotic cutaneous leishmaniasis (ZCL, 181 persons), anthroponotic cutaneous leishmaniasis (ACL, 104 persons), and zoonotic visceral leishmaniasis (ZVL, 67 persons) are endemic. The percentage of persons with an IFN-γ-positive response (> 0.2 IU/mL) to three antigens and the mean concentration of IFN-γ induced by the antigens were higher for persons from areas endemic for ZVL than for persons from areas endemic for ZCL and ACL. The percentage of persons with LST-positive results (≥ 5 mm indurations) was 99%, 94%, and 70% for areas with ZCL, ACL, and ZVL, respectively. Our data indicate that the LST is significantly more sensitive than IFN-γ levels in persons who have been cured of cutaneous leishmaniasis than in persons who have been cured of ZVL.


Assuntos
Antígenos de Protozoários/imunologia , Interferon gama/sangue , Leishmaniose/sangue , Adolescente , Adulto , Idoso , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Leishmaniose/epidemiologia , Leishmaniose/imunologia , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , Adulto Jovem
20.
Orv Hetil ; 152(43): 1739-44, 2011 Oct 23.
Artigo em Húngaro | MEDLINE | ID: mdl-21983400

RESUMO

UNLABELLED: Psychoneuroimmunologic studies on positive emotions are few, and their clinical relevance is limited. AIMS: This "SHoRT" (Smiling Hospital Research Team) study evaluates the effects that Smiling Hospital artists have on hospitalized children. METHODS: Blood samples were taken in a non-painful way through branules in an accredited Infectology Ward, 30 minutes before and 1 hour after a visit of tale tellers, puppeteers and handicraft artists. 24 children were visited and 9 were included in the control group. Blood lymphocyte counts and Th1/Th2 cytokine levels were determined. Artists evaluated their effect on a subjective scale. RESULTS: In the visited group, the increase of lymphocytes was 8.43% higher, the decrease was 12.45% lower, and the proportion of children showing increased lymphocyte counts was more increased. Changes were more marked after more successful visits. Authors found non-significant, still considerable changes in interferon-γ level (p < 0.055) and in Th1/Th2 cytokine ratios. CONCLUSIONS: This pediatric study suggests that immunological changes may develop when more attention is given to hospitalized children.


Assuntos
Criança Hospitalizada , Citocinas/imunologia , Felicidade , Sorriso , Células Th1/imunologia , Células Th2/imunologia , Adolescente , Criança , Criança Hospitalizada/psicologia , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Citocinas/sangue , Feminino , Citometria de Fluxo , Fundações , Hospitais de Ensino , Humanos , Hungria , Lactente , Interferon gama/sangue , Interleucinas/sangue , Linfotoxina-alfa/sangue , Masculino , Fatores de Tempo
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