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1.
PLoS One ; 15(9): e0239532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976531

RESUMO

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.


Assuntos
Linfócitos T CD4-Positivos/patologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Citocinas/sangue , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Adolescente , Adulto , Idoso , Betacoronavirus , Contagem de Linfócito CD4 , Relação CD4-CD8 , Criança , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Interleucina-6/sangue , Linfopenia/sangue , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
2.
Lancet HIV ; 7(8): e565-e573, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32763219

RESUMO

BACKGROUND: A low CD4/CD8 ratio during antiretroviral therapy (ART) identifies people with heightened immunosenescence and increased risk of mortality. We aimed to assess the effects of integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART on long-term CD4/CD8 ratio recovery. METHODS: This prospective cohort study included 13 026 individuals with HIV registered in the Spanish HIV Research Network (CoRIS) cohort recruited from 45 Spanish hospitals. We included HIV-positive people who started triple ART (two nucleoside reverse transcriptase inhibitors [NRTI] with a NNRTI, protease inhibitor, or INSTI) and had HIV RNA suppression within 48 weeks. We used piecewise linear mixed models adjusted for potential confounders to compare longitudinal changes in the CD4/CD8 ratio between people receiving three different types of ART. We used Cox proportional-hazard models to compare the times to CD4/CD8 normalisation between the treatment groups, using cutoff ratios of 0·4, 1·0, and 1·5. FINDINGS: 6804 individuals contributing 37 149 persons-years and 37 680 observations were analysed; median follow-up was 49 months (IQR 22-89). INSTI-based ART was associated with greater CD4/CD8 gain (change per year compared with INSTI was coefficient -0·07 [95% CI -0·08 to -0·06] for NNRTI and was -0·08 [-0·09 to -0·08] for protease inhibitors). Differences were observed from the first year of therapy and were driven by changes in both CD4 and CD8 cell counts. Subanalyses at different time periods suggested that these differences were driven by changes during the first year of ART without significant differences in the adjusted CD4/CD8 ratio trajectories after the second year of ART (change per year compared with INSTI was coefficient -0·03 [95% CI -0·05 to -0·13] for NNRTI and was -0·06 [95% CI -0·08 to -0·04] for protease inhibitors). Although no differences in the time until CD4/CD8 normalisation at a cutoff ratio of no less than 0·4 were reported between any of the groups, compared with the INSTI group, both the NNRTI and protease inhibitor groups showed lower rates of normalisation at cutoff ratios of 1·0 or more (adjusted hazard ratio 0·80 [95% CI 0·72-0·89] for the NNRTI group and 0·79 [0·69-0·89] for the protease inhibitor group), and 1·5 or more (0·79 [0·65-0·95] for the NNRTI group and 0·78 [0·64-0·97] for the protease inhibitor group). No differences were found between the different integrases in the time until CD4/CD8 normalisation. Subanalyses adjusted for the backbone NRTIs and allowing observations after virological failure yielded similar results. INTERPRETATION: This study provides new evidence that reinforces the positioning of INSTI-based therapies as a first choice and underlines the importance of analysing the effects of therapeutic interventions on biomarkers linked with morbidity and mortality beyond the plasma HIV RNA and the CD4 cell counts. FUNDING: Spanish AIDS Research Network (Instituto de Salud Carlos III), European Development Regional Fund "A way to achieve Europe".


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Relação CD4-CD8 , Linfócitos T CD8-Positivos , Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/administração & dosagem , Biomarcadores Farmacológicos/análise , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha
3.
BMC Infect Dis ; 20(1): 571, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758162

RESUMO

BACKGROUND: The incidence of cryptococcal meningitis (CM) has gradually increased in recent years. Cerebrospinal fluid (CSF) cytology and cell count are very important for CM on etiology diagnosis and assessment of disease status and therapeutic response. However, the clinical significance of CSF white cell count (WCC) in CM patients is not fully understood. Using longitudinal data of CSF WCC and its relationship with clinical outcomes in CM patients, we aimed to elucidate the clinical significance of this test. METHODS: We retrospectively analyzed the medical records of 150 CM patients admitted to our hospital between January 2008 and December 2018. RESULTS: CM patients with lower baseline CSF WCC, CSF protein concentration or CD4/CD8 ratio, and those with altered mentation or HIV coinfection were more likely to have poor clinical outcome (P<0.05). CM patients with triple therapy during the induction period presented with a better clinical outcome (P<0.05). Baseline CSF WCC had a moderate positive correlation with peripheral CD4+ T lymphocyte count (r = 0.738, P < 0.001) and CD4+ T lymphocyte percentage (r = 0.616, P < 0.001). The best cut-off value to predict a poor clinical outcome was 40 cells/µL during baseline CSF WCC. The predictive model incorporating longitudinal data of CSF WCC had better sensitivity, specificity, and accuracy than a model incorporating only baseline CSF WCC data. CONCLUSIONS: Our results indicated that baseline CSF WCC and changes in CSF WCC over time could be used to assess the prognosis of CM patients.


Assuntos
Relação CD4-CD8/métodos , Cryptococcus neoformans , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/diagnóstico , Adulto , Antirretrovirais/uso terapêutico , Antifúngicos/uso terapêutico , China , Confiabilidade dos Dados , Feminino , Previsões/métodos , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Estudos Longitudinais , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
4.
Mult Scler ; 26(10): 1261-1264, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32762494

RESUMO

Approximately 200,000 multiple sclerosis (MS) patients worldwide receive B-cell-depleting immunotherapy with rituximab (anti-CD20), which eliminates the ability to generate an antibody response to new infections. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies might help viral clearance, these patients could be at risk of severe complications if infected. Here, we report on an MS patient who had received rituximab for ~3 years. The patient was examined 5 days before the onset of coronavirus disease 2019 (COVID-19) symptoms and was admitted to the hospital 2 days after. She recovered 14 days after symptom onset despite having a 0% B lymphocyte count and not developing SARS-CoV-2 immunoglobulin G (IgG) antibodies.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular/imunologia , Células Matadoras Naturais/imunologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Pneumonia Viral/imunologia , Rituximab/uso terapêutico , Betacoronavirus , Relação CD4-CD8 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia
5.
Front Immunol ; 11: 1648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754159

RESUMO

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Cuidados Críticos/métodos , Citocinas/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Tomada de Decisão Clínica/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Estado Terminal , Células Endoteliais/metabolismo , Feminino , Humanos , Hospedeiro Imunocomprometido , Interleucina-6/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Masculino , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Fatores Sexuais , Trombose
6.
Life Sci ; 258: 118167, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735885

RESUMO

AIMS: This study aimed to make a comparison between the clinical laboratory-related factors, complete blood count (CBC) indices, cytokines, and lymphocyte subsets in order to distinguish severe coronavirus disease 2019 (COVID-19) cases from the non-severe ones. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, Scopus, and Web of Science databases until March 31, 2020. Cochrane's Q test and the I2 statistic were used to determine heterogeneity. We used the random-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). KEY FINDINGS: Out of a total of 8557 initial records, 44 articles (50 studies) with 7865 patients (ranging from 13 to 1582), were included. Our meta-analyses with random-effect models showed a significant decrease in lymphocytes, monocyte, CD4+ T cells, CD8+ T cells, CD3 cells, CD19 cells, and natural killer (NK) cells and an increase in the white blood cell (WBC), neutrophils, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP)/hs-CRP, erythrocyte sedimentation rate (ESR), ferritin, procalcitonin (PCT), and serum amyloid A (SAA), interleukin-2 (IL-2), IL-2R, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1ß, IL-17, and CD4/CD8 T cell ratio between the two groups. SIGNIFICANCE: Decrease in total lymphocytes and lymphocyte subsets as well as the elevation of CRP, ESR, SAA, PCT, ferritin, and cytokines, but not IL-1ß and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Citocinas/sangue , Linfócitos/imunologia , Pneumonia Viral/sangue , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Relação CD4-CD8 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Humanos , Contagem de Linfócitos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Prognóstico
9.
J Infect Dis ; 222(2): 198-202, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32379887

RESUMO

This study evaluated the significance of lymphocyte subset detection in peripheral blood in the diagnosis and prognosis of coronavirus disease 2019 (COVID-19). Our results revealed that CD3+ T cells, CD4+ T cells, CD8+ T cells, and natural killer cells were significantly decreased in patients with COVID-19. These patients had a relatively slight decrease in CD4+ T cells but a severe decrease in CD8+ T cells. The significantly elevated CD4/CD8 ratio was observed in COVID-19 patients. T-cell subset counts were related to the severity and prognosis of COVID-19, suggesting that the counts of CD8+ T and CD4+ T cells can be used as diagnostic markers of COVID-19 and predictors of disease severity.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Contagem de Linfócitos , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Subpopulações de Linfócitos T , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD8-Positivos , Feminino , Humanos , Células Matadoras Naturais , Masculino , Pessoa de Meia-Idade , Pandemias , Gravidade do Paciente , Sensibilidade e Especificidade , Adulto Jovem
10.
PLoS One ; 15(5): e0233049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442166

RESUMO

BACKGROUND: The role of CD4/CD8 ratio on the incidence of tuberculosis (TB) in patients on antiretroviral therapy (ART) is unknown. Thus, we sought to determine whether the CD4/CD8 ratio was associated with development of TB in a cohort of HIV infected individuals on ART followed up for more than a decade in the setting of sub-Saharan Africa (SSA). METHODS: The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 15 years. Clinical data were collected in retrospective manner. Patients with an AIDS defining illness or a CD4 count <200 cell/µL were started with a combination of ART. The participants have clinic visits every 6 months and/or as needed. Poisson regression models were used to identify factors associated with development of incident TB. Kaplan-Meier curves were used to estimate the probability of incident TB while on ART. RESULTS: A total of 347 patients with a median duration of follow-up on ART of 11.5 (IQR: 10.0-12.5) years were included. Incident TB developed in 47 patients during the 3259 person-years of follow-up, the majority (76.6%) occurred within five year of ART initiation. On univariate analysis, poor ART adherence (RR:2.57, 95% CI: 1.28-5.17), time-updated CD4 cell count of lower than 200 (RR: 4.86, 95%CI 2.33-10.15), or CD4 cell count between 200 and 500 (RR: 4.68, 95% CI: 2.17-10.09), time-updated CD8 cell count lower than 500 (RR: 2.83 95% CI 1.31-6.10), or CD8 cell count over 1000 (RR: 2.23, 95% CI: 1.12-4.45), time-updated CD4/CD8 ratio of less than 0.30 (RR: 6.00, 95% CI: 2.96-12.14), lack of normalization of CD4 T-cell count (RR: 6.13, 95% CI: 2.20-17.07), and virological failure (RR: 2.35 (95% CI: 1.17-4.71) were all associated with increased risk of incident TB. In multivariate analysis, however, time-updated CD4/CD8 ratio of less than 0.30 (adjusted RR: 4.08, 95% CI: 1.31-12.68) was the only factor associated with increased risk of developing incident TB (p = 0.015). Similar results were obtained in a sensitivity analysis by including only those virally suppressed patients (n = 233, 69% of all patients). In this group, CD4/CD8 ratio of less than 0.30 was associated with development of incident TB (adjusted RR: 4.02, 95% CI: 1.14-14.19, p = 0.031). Overall, the incidence rate of TB in patients with an updated CD4/CD8 ratio of less than 0.30 was more than 5-fold higher when compared with those with a ratio more than 0.45. CONCLUSION: Low CD4/CD8 ratio is independently associated with an increased risk of incident TB despite viral suppression. CD4/CD8 ratio may serve as a biomarker for identifying patients at risk of TB in patients on ART in the setting of SSA.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Tuberculose/epidemiologia , Adulto , África ao Sul do Saara/epidemiologia , Relação CD4-CD8 , Feminino , Infecções por HIV/imunologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Distribuição de Poisson , Estudos Retrospectivos
11.
PLoS One ; 15(4): e0231761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353005

RESUMO

BACKGROUND: Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated with HIV immune dysregulation. METHODS: PLWH ≥40 years old and on stable ART ≥3 months were enrolled (N = 149). OXPHOS complex I (CI, NADH dehydrogenase) and complex IV (CIV, cytochrome c oxidase) protein levels in PBMCs were quantified using immunoassays. Monocyte subsets and markers of T-cell activation, senescence, and exhaustion were measured on PBMC by flow cytometry. Plasma inflammatory mediators were quantified using a multiplex assay. HIV-uninfected group (N = 44) of similar age, gender, and ethnicity had available OXPHOS levels. RESULTS: PLWH had a median age of 51 years. Majority were male (88.6%), Caucasian (57.7%), and with undetectable plasma HIV RNA <50 copies/mL (84.6%). Median CI level was lower in PLWH compared with the HIV-seronegative group (65.5 vs 155.0 optical density/µg protein x 103, p <0.0001). There was no significant difference in median CIV levels. Lower OXPHOS levels correlated with lower CD4% and CD4/CD8 ratio. On multivariable linear regression adjusted for age, current use of zidovudine/didanosine, and HIV RNA (detectable versus undetectable), lower OXPHOS levels were significantly associated with higher MPO, SAA, SAP, and sVCAM, and higher frequencies of intermediate (CD14++CD16+) monocytes and TIGIT+TIM3+ CD4 T-cell (p<0.01). CONCLUSION: CI PBMC protein levels were decreased in PLWH on ART. Decreased OXPHOS correlated with disease severity and inflammation. Further studies on the relationship between immunometabolism and immune dysregulation in HIV are warranted.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/imunologia , HIV-1/imunologia , Leucócitos Mononucleares/imunologia , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Relação CD4-CD8 , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Hawaii , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos Mononucleares/citologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mitocôndrias/imunologia , RNA Viral/isolamento & purificação , Índice de Gravidade de Doença
12.
Blood Cells Mol Dis ; 83: 102437, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-47354

RESUMO

BACKGROUND: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. METHODS: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. RESULTS: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). CONCLUSION: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.


Assuntos
Betacoronavirus/imunologia , Antígenos CD8/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Pneumonia Viral/imunologia , Betacoronavirus/isolamento & purificação , Biomarcadores/análise , Relação CD4-CD8 , Antígenos CD8/análise , Linfócitos T CD8-Positivos/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia
13.
Blood Cells Mol Dis ; 83: 102437, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32325421

RESUMO

BACKGROUND: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. METHODS: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. RESULTS: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). CONCLUSION: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.


Assuntos
Betacoronavirus/imunologia , Antígenos CD8/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Pneumonia Viral/imunologia , Betacoronavirus/isolamento & purificação , Biomarcadores/análise , Relação CD4-CD8 , Antígenos CD8/análise , Linfócitos T CD8-Positivos/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia
14.
Clin Exp Immunol ; 201(1): 85-93, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32275772

RESUMO

Pulmonary sarcoidosis is characterized by an exaggerated CD4+ T cell response and formation of non-necrotizing granulomas. Tumour necrosis factor α (TNF-α) is regarded as crucial for granuloma formation and TNF-α inhibitors offer a third-line treatment option for patients not responding to conventional treatment. However, not all patients benefit from treatment, and an optimal dose and treatment duration have not been established. Insight into the influence of TNF-α inhibitors on lung immune cells may provide clues as to what drives inflammation in sarcoidosis and improve our understanding of treatment outcomes. To evaluate the effects of treatment with the TNF-α inhibitor infliximab on lung immune cells and clinical features of the patients, 13 patients with sarcoidosis refractory to conventional treatment were assessed with bronchoalveolar lavage (BAL), spirometry and computerized tomography (CT) scan closely adjacent to the start of infliximab treatment. These investigations were repeated after 6 months of treatment. Treatment with TNF-α inhibitor infliximab was well tolerated with no adverse events, except for one patient who developed a probable adverse event with liver toxicity. Ten patients were classified as responders, having a reduced CD4/CD8 ratio, a decreased percentage of CD4+ T cells expressing the activation marker CD69 and number of mast cells (P < 0·05 for all). The percentage of T regulatory cells (Tregs ), defined as forkhead box P3+ CD4+ T cells decreased in most patients. In conclusion, six months of infliximab treatment in patients with sarcoidosis led to signs of decreased CD4+ T cell alveolitis and decreased mastocytosis in the lungs of responders.


Assuntos
Infliximab/administração & dosagem , Pulmão/imunologia , Sarcoidose Pulmonar , Linfócitos T Reguladores/imunologia , Adulto , Lavagem Broncoalveolar , Relação CD4-CD8 , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/imunologia , Sarcoidose Pulmonar/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X
15.
Klin Lab Diagn ; 65(1): 24-28, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32155003

RESUMO

In this study was made an attempt to reveal additional laboratory markers of white blood for preliminary estimation level of HIV-infection development. Essentially such markers these are in progress without complex equipment and expensive reagent. It was studied alterations of basic values cells of innate and acquired immunity of peripheral blood HIV-infected individuals with and without antiretroviral treatment (ART) during infection. It was estimate value leukocytes, neutrophils, monocytes, lymhpocytes, T-lymhpocytes, CD4+, CD8+ T-cells, CD4/CD8 index. It was used the first analysis in the time of registration for regular medical check-up and the intermediate derived during 2017-2018 years. Patients without ART and with ART before and after treatment had rates of leukocytes, lymhpocytes, T-lymhpocytes, monocytes and neutrophils within the normal guideline. Essential changes were observed in basic conventional laboratory parameters evaluation of HIV-infection dynamic (parameters of CD4+, CD8+ T-cells, CD4/CD8 index). Thereby it was impossible to reveal supplementary immunological markers of HIVinfection.


Assuntos
Imunidade Adaptativa , Infecções por HIV/imunologia , Imunidade Celular , Terapia Antirretroviral de Alta Atividade , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , Humanos
16.
Int J Hematol ; 111(6): 771-778, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32162096

RESUMO

In the present study, we analyzed phenotypes of cells in the lymphocyte region of bone marrow in 68 patients with primary immune thrombocytopenia (ITP) to determine whether cellular phenotype predicts response to first-line therapy (corticosteroids or corticosteroids plus intravenous immunoglobulin). In 52 newly diagnosed ITP patients, an abnormal CD4:CD8 ratio (CD4/CD8 ratio < 0.4 and 2.3 < CD4/CD8 ratio) was noted in 22 patients in the responder group, whereas all non-responder and control individuals showed normal CD4:CD8 ratio (p < 0.001). The absolute number of CD19+ cells in patients with 0.4 ≤ CD4/CD8 ratio ≤ 2.3 or 2.3 < CD4/CD8 ratio was higher than that in other groups. (p = 0.016). In 16 chronic ITP patients, the absolute number of NK cells in the responder group was lower than those in the non-responder and control groups (p = 0.032). An abnormal CD4:CD8 ratio was noted in all patients in the responder group, whereas all patients in non-responder and control groups showed normal CD4:CD8 ratio (p < 0.001). The present results indicate that CD4:CD8 ratio, B cells, and NK cells contribute to the prediction of therapeutic outcomes of ITP patients.


Assuntos
Células da Medula Óssea/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Subpopulações de Linfócitos , Prednisona/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Antígenos CD19 , Linfócitos B , Relação CD4-CD8 , Citometria de Fluxo , Células Matadoras Naturais , Fenótipo , Valor Preditivo dos Testes , Resultado do Tratamento
17.
J Immunol Res ; 2020: 2714257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149156

RESUMO

Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4+/CD8+ ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.


Assuntos
Adjuvantes Imunológicos , Panax/química , Saponinas/farmacologia , Selênio/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Vacinas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Biomarcadores , Relação CD4-CD8 , Citocinas/metabolismo , Feminino , Expressão Gênica , Imunoglobulina G/imunologia , Camundongos , Vacinas contra Pseudorraiva/imunologia , Saponinas/química , Selênio/química , Soluções , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Suínos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo
18.
Arthritis Rheumatol ; 72(7): 1091-1102, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32039570

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated through complex immunologic pathways. Among RA patients receiving low-dose methotrexate (MTX) monotherapy, approximately one-half exhibit a meaningful clinical response within the first 6 months of starting treatment. Whether baseline immune phenotypes differ between subsequent MTX responders and nonresponders is unknown. This study utilized comprehensive T cell immunophenotyping to identify specific immunologic pathways associated with MTX-nonresponsive joint inflammation in patients with RA. METHODS: In total, 32 patients with recent-onset RA were treated with MTX therapy. After 6 months, 15 patients were categorized as responders and 17 as nonresponders. Comprehensive blood T cell immunophenotyping, using multiparameter immunofluorescence flow cytometry analyses, was performed at baseline and following 6 months of treatment. RESULTS: Baseline measures of disease activity (Disease Activity Score in 28 joints [DAS28], C-reactive protein level, and erythrocyte sedimentation rate) did not differ between MTX responders and nonresponders following MTX treatment. Frequencies of CD4+ and CD8+ T cells were skewed to favor higher CD4:CD8 T cell ratios in MTX responders compared to nonresponders (P < 0.05). The proportion of inducible costimulator-expressing Treg cells was significantly greater among MTX nonresponders. Interleukin-13 (IL-13)-producing, but not interferon-γ- or IL-17-producing, CD4+ effector memory T (Tem) cells were significantly more frequent in MTX nonresponders (P < 0.05). The ratio of IL-13+:IL-17+ Tem cells among CD4+ Tem cells was 1.9-fold higher in MTX nonresponders compared to responders (P < 0.05). Both the CD4:CD8 T cell ratio and the frequency of IL-13+CD4+ Tem cells correlated with changes in the DAS28 score following MTX treatment, whereas T cell expression of immune checkpoint inhibitor markers (CTLA-4, programmed death 1, and T cell immunoglobulin and mucin domain-containing protein 3) did not differ between MTX responders and nonresponders. CONCLUSION: We observed a bias toward type 2-polarized T cell inflammatory responses in the peripheral blood of MTX-nonresponsive RA patients. Targeting the IL-13+CD4+ T cell pathway could be a new therapeutic strategy in RA patients whose disease remains resistant to MTX.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Linfócitos T/imunologia , Adulto , Idoso , Artrite Reumatoide/imunologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Antígeno CTLA-4/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Memória Imunológica/imunologia , Imunofenotipagem , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Interferon gama/imunologia , Interleucina-13/imunologia , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Falha de Tratamento , Resultado do Tratamento
19.
Artigo em Inglês | MEDLINE | ID: mdl-32032279

RESUMO

BACKGROUND: To evaluate differences between older women and men with HIV regarding HIV variables, comorbidity, physical function, and quality of life (QOL). SETTING: The Modena HIV clinic. METHODS: Prospective cohort study. Cross-sectional analysis. Patients >50 years were included, stratified by sex. We recorded sociodemographic data, comorbidities, variables related to HIV infection, frailty, data on body composition, physical function, physical activity, and QOL. RESULTS: We evaluated 1126 older adults with HIV, of which 284 (25.2%) were women. Median age was 55 (IQR 6) years. There were significant differences between women and men in the median current CD4 T-cell and the mean CD4/CD8 ratio. There were differences regarding alcohol consumption, cardiovascular (CV) disease, hypertension, diabetes mellitus, and renal failure. Sarcopenia and slower gait speed were found more prevalent among men, but without significant differences. Significant differences were found regarding lower extremity strength measured by the chair stand test and in the short physical performance battery score. Short physical performance battery <9 was detected for 11.1% women vs. 5.6% men (P = 0.002). EQ5D5L score was 0.87 in women vs. 0.89 in men (P = 0.002). CONCLUSIONS: In our cohort, older women represented one in 4 of the total patients. Despite the fact that women have better immunological recovery measured by CD4 T-cell count and CD4/CD8 ratio, and fewer CV disease and CV risk factors than men, their physical function and their QOL are worse. Therefore, older HIV-infected women have special characteristics, and the assessment of physical function in this group seems to be crucial.


Assuntos
Composição Corporal , Fragilidade , Infecções por HIV/complicações , Força Muscular , Idoso , Envelhecimento , Consumo de Bebidas Alcoólicas , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD4-Positivos , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
PLoS One ; 15(1): e0226724, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945066

RESUMO

BACKGROUND: Multiple T-cell marker recovery (MTMR: CD4+ T-cells >500 cel/mm3 plus CD4+% >29% plus CD4+/CD8+ ratio >1) has been proposed as the most complete level of immune reconstitution. In this study we quantified differences in the CD4+/CD8+ ratio, CD4+% recovery and MTMR after starting HIV-1 treatment with dolutegravir (DTG) vs. raltegravir (RAL) plus a NRTI backbone. METHODS: Exploratory post-hoc analysis of the SPRING-2 study, a randomized double-blind clinical trial comparing DTG and RAL as third agents in naive HIV-infected patients at 100 sites in Canada, USA, Australia, and Europe. Percentage differences and corresponding precision based on 95% confidence intervals (CI) and p-values were calculated for i) CD4+/CD8+ ratio normalization, ii) CD4+% normalization, and iii) the achievement of MTMR. RESULTS: A total of 822 participants were analyzed (411 in each group). No statistically significant differences in the proportion of patients who reached a CD4+/CD8+ ratio ≥0.5 & ≥1 at w48 & w96 were observed. At w96, the proportion of patients with a CD4+/CD8+ ratio ≥1 was similar (30.43% DTG vs. 29.57% RAL). No differences were observed in the mean increase in CD4+/CD8+ ratio from baseline at both w48 & w96. Similarly, no significant differences in the CD4+/CD8+>29% were observed at w96 (72.95% DTG vs 69.28% RAL). The proportion of patients attaining MTMR criteria was also similar in the DTG group and the RAL group at w48 (20.33% vs. 18.26%; difference 2.07 (95%CI (-3.67;7.81) P = 0.481 and w96 (28.70% vs. 27.13; difference 1.56 (95%CI -5.22;8.34) P = 0.652). CONCLUSION: After comparing DTG and RAL, no differences on immune recovery markers were observed.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Biomarcadores/análise , Relação CD4-CD8 , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Método Duplo-Cego , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Masculino , Carga Viral
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