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1.
Front Immunol ; 12: 720952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531867

RESUMO

The ongoing COVID-19 pandemic has increased awareness about sex-specific differences in immunity and outcomes following SARS-CoV-2 infection. Strong evidence of a male bias in COVID-19 disease severity is hypothesized to be mediated by sex differential immune responses against SARS-CoV-2. This hypothesis is based on data from other viral infections, including influenza viruses, HIV, hepatitis viruses, and others that have demonstrated sex-specific immunity to viral infections. Although males are more susceptible to most viral infections, females possess immunological features that render them more vulnerable to distinct immune-related disease outcomes. Both sex chromosome complement and related genes as well as sex steroids play important roles in mediating the development of sex differences in immunity to viral infections.


Assuntos
COVID-19/patologia , Índice de Gravidade de Doença , Caracteres Sexuais , Contagem de Linfócito CD4 , Relação CD4-CD8 , Citocinas/sangue , Feminino , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Masculino , SARS-CoV-2/imunologia , Fatores Sexuais
2.
Clin Infect Dis ; 73(1): 50-59, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34370842

RESUMO

BACKGROUND: A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH. METHODS: PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations. RESULTS: We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23-3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58-6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60-6.56] for KS; HR = 5.28 [95% CI = 2.17-12.83] for NHL). CONCLUSIONS: Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.


Assuntos
Infecções por HIV , Linfoma não Hodgkin , Sarcoma de Kaposi , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD8-Positivos , Estudos de Coortes , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Linfoma não Hodgkin/epidemiologia , Fatores de Risco , Sarcoma de Kaposi/epidemiologia
3.
PLoS One ; 16(7): e0254149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320023

RESUMO

OBJECTIVE: Serious non-AIDS disease events (SNAE) are experienced disproportionately by immunologic non-responders (INRs), HIV-infected individuals who do not restore CD4 T cells in blood despite effective viral suppression. We aimed to characterize the inflammatory biomarker profile of the INR phenotype. METHODS: Blinded cross-sectional cohort study comparing markers of immune activation and gut homing between INR and non-INR individuals. HIV-positive participants had HIV RNA suppression on antiretroviral therapy and were categorized as either INR (N = 36) or Clinical Responders ("CR"; CD4>350/mm3; N = 47). 18 HIV-negative comparator individuals were included. Cellular markers were assessed by flow cytometry, with soluble markers assessed by ELISA and LC/MS-MS. Multivariable linear regression models estimated the association between INR phenotype and markers, adjusting for age, sex, duration of ART, and recent infection/vaccination. RESULTS: INR participants demonstrated a reduced CD4/CD8 ratio (p<0.001), 35% more CD8 activation (p = 0.02), 36% greater α4ß7+ CD4 T cells (p<0.01), 54% more HLA-DR+ CD4 T cells (p<0.001), and 20% higher plasma VCAM (p<0.01) compared to CRs. The INR phenotype was not associated with levels of Kyn/Trp, CRP, TNF, IFNγ, IL-8, IL-6, sCD14, D-Dimer, I-FABP, MCP-1, ICAM or CD8%HLA-DR+. CONCLUSIONS: Peripheral CD4 non-recovery during long-term treated HIV infection is characterized by elevated CD8 activation and CD4 gut homing. Gut-focused interventions may be warranted in the INR context, and CD8 activation may serve as a surrogate endpoint for clinical interventions.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Antígenos HLA-DR/metabolismo , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Modelos Lineares , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Fenótipo , Falha de Tratamento , Molécula 1 de Adesão de Célula Vascular/sangue
4.
J Immunol Res ; 2021: 6657894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150910

RESUMO

Background: The 2019 novel coronavirus SARS-CoV-2 caused large outbreaks of COVID-19 worldwide. COVID-19 resembles community-acquired pneumonia (CAP). Our aim was to identify lymphocyte subpopulations to distinguish between COVID-19 and CAP. Methods: We compared the peripheral blood lymphocytes and their subsets in 296 patients with COVID-19 and 130 patients with CAP. Parameters for independent prediction of COVID-19 were calculated by logistic regression. Results: The main lymphocyte subpopulations (CD3+CD4+, CD16+CD56+, and CD4+/CD8+ ratio) and cytokines (TNF-α and IFN-γ) of COVID-19 patients were significantly different from that of CAP patients. CD16+CD56+%, CD4+/CD8+ratio, CD19+, and CD3+CD4+ were identified as predictors of COVID-19 diagnosis by logistic regression. In addition, the CD3+CD4+counts, CD3+CD8+ counts, andTNF-α are independent predictors of disease severity in patients. Conclusions: Lymphopenia is an important part of SARS-CoV-2 infection, and lymphocyte subsets and cytokines may be useful to predict the severity and clinical outcomes of the disease.


Assuntos
Relação CD4-CD8 , COVID-19/sangue , Interferon gama/sangue , Subpopulações de Linfócitos/citologia , Pneumonia/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , COVID-19/imunologia , COVID-19/patologia , Teste para COVID-19 , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Subpopulações de Linfócitos/imunologia , Linfopenia/sangue , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia/imunologia , Pneumonia/patologia , Prognóstico , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
5.
Lancet HIV ; 8(6): e317-e318, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34087093
6.
Front Immunol ; 12: 663412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079548

RESUMO

Endothelial inflammation and damage are the main drivers of cardiovascular risk/disease. Endothelial repair is mediated in part by recruitment of bone marrow endothelial progenitor/endothelial colony forming cells (EPC/ECFC). People with HIV (PWH) have increased cardiovascular risk and the impact of infection in endothelial repair is not well defined. The low frequencies and challenges to in vitro isolation and differentiation of EPC/ECFC from PBMCs had made it difficult to study their role in this context. We hypothesized that HIV driven inflammation induces phenotypic changes that reflects the impact of infection. To test this hypothesis, we evaluated expression of markers of trafficking, endothelial differentiation, and angiogenesis, and study their association with biomarkers of inflammation in a cohort of PWH. In addition, we investigated the relationship of circulating endothelial progenitors and angiogenic T cells, a T cell subset with angiogenic function. Using a flow cytometry approach, we identified two subsets of circulating progenitors LIN4-CD45-CD34+ and LIN4-CD45dimCD34+ in PWH. We found that the phenotype but not frequencies were associated with biomarkers of inflammation. In addition, the percentage of LIN4-CD45dimCD34+ was associated with serum levels of lipids. This data may provide a new tool to better address the impact of HIV infection in endothelial inflammation and repair.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Infecções por HIV/complicações , Infecções por HIV/imunologia , Vasculite/etiologia , Vasculite/metabolismo , Idoso , Biomarcadores , Relação CD4-CD8 , Doença Crônica , Células Progenitoras Endoteliais/patologia , Feminino , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Imunofenotipagem , Mediadores da Inflamação , Metabolismo dos Lipídeos , Lipídeos/sangue , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Vasculite/patologia
7.
Sci Rep ; 11(1): 9381, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931705

RESUMO

Pleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.


Assuntos
Biomarcadores Tumorais/análise , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/mortalidade , Derrame Pleural Maligno/imunologia , Idoso , Linfócitos T CD8-Positivos/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
Artigo em Inglês | MEDLINE | ID: mdl-33865542

RESUMO

The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.


Assuntos
Instabilidade Genômica , Infecções por HIV/genética , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Instabilidade Genômica/efeitos dos fármacos , HIV/efeitos dos fármacos , HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacos , Carga Viral/fisiologia , Adulto Jovem
9.
PLoS One ; 16(3): e0248675, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735325

RESUMO

BACKGROUND: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19. METHODS: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old. RESULTS: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups. CONCLUSIONS: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.


Assuntos
COVID-19/epidemiologia , Fatores Etários , Idoso , Relação CD4-CD8 , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Estado Terminal , Feminino , Humanos , Imunidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
10.
Front Immunol ; 12: 624789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717135

RESUMO

Objective: Transarterial chemoembolization (TACE) stands for an ideal therapy for patients with intermediate stage HCC. This study was carried out to observe the effect of microparticles-transarterial chemoembolization (microparticles-TACE, m-TACE) on the immune function of hepatocellular carcinoma (HCC) patients by detecting the proportion of regulatory (Treg) cells in the peripheral blood of HCC patients before and after m-TACE, and to determine whether m-TACE has a positive regulatory effect on the immune function of HCC patients. Methods: 33 HCC patients treated with Gelatn Sponge Microparticles (GSMs-TACE) were enrolled. Flow cytometry was used to determine the proportion of Treg cells and CD4+/CD8+ T cells in peripheral blood of HCC patients 1 day before GSMs-TACE, 1 to 2 weeks and 3 to 5 weeks after GSMs-TACE, respectively. Results: The Tregs cell proportion of HCC patients was significantly higher than that of the healthy and cirrhosis controls and was associated with various clinical indicators of HCC patients. The Treg cell proportion in HCC patients with BCLC stage C was higher than that of stage B patients; The Treg cell proportion at 1 to 2 weeks postoperatively was 8.54 ± 1.27%, which was significantly lower than that before the GSMs-TACE. The Treg cell proportion at 3 to 5 weeks postoperatively was 7.59 ± 1.27%, which continued to decline. The ratio of CD4+/CD8+ T cells was 1.31 ± 0.56, 1.86 ± 0.73, 1.76 ± 0.58% (P<0.01) respectively. Conclusion: These results indicated that m-TACE could exert a positive regulatory effect on the anticancer immune function of HCC patients, which may be used in combination with immune adjuvant therapies to enhance the efficacy of HCC.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Epirubicina/administração & dosagem , Neoplasias Hepáticas/terapia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Relação CD4-CD8 , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/imunologia , Estudos de Casos e Controles , Portadores de Fármacos , Feminino , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Fatores de Tempo , Resultado do Tratamento
11.
Int Immunopharmacol ; 95: 107531, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33714884

RESUMO

PURPOSE: Researches revealed that probiotics maybe a potential strategy for COVID-19, whereas there is a lack of related evidence. This study aims to analyze the role of probiotics on severe COVID-19 patients. METHODS: In the current retrospective single-center study, we collected data of 311 consecutive severe patients with confirmed COVID-19 in Wuhan Union Hospital from Feb 3rd to Feb 20th, 2020. Epidemiological, clinical and medication characteristics were compared and analyzed between patients with or without probiotics. RESULTS: In total, 93 of the 123 patients (75.61%) who were treated with probiotics survived to hospital discharge with the median inpatient day of 32 days and mean virus clearance time of 23 days, which were significantly longer than those of patients without probiotics. There were no bias in laboratory parameters, except for IL-6 and ESR, which were significantly higher in patients treated probiotics. We tracked the dynamic changes of 8 selected laboratory parameters (IL-6, CRP, total T lymphocytes, NK cells, B lymphocyte, CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) and found that probiotics could not reduce the increased IL-6 levels but possessed the ability to moderate the immunity and decreased the incidence of secondary infection in COVID-19 patients. CONCLUSIONS: Probiotics could be an effective strategy for the treatment of COVID-19 patients to reduce the secondary infection and moderated the immunity.


Assuntos
COVID-19/terapia , Probióticos/uso terapêutico , Idoso , Linfócitos B/imunologia , Relação CD4-CD8 , COVID-19/sangue , COVID-19/imunologia , Feminino , Humanos , Inflamação/terapia , Interleucina-6/sangue , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Receptores Imunológicos/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Linfócitos T/imunologia , Resultado do Tratamento
12.
Ann Hematol ; 100(4): 995-1002, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33651193

RESUMO

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3+ T-lymphocyte count (ACD3C), CD4+ T-lymphocyte count (ACD4C), CD8+ T-lymphocyte count (ACD8C), and CD4+/CD8+ T-lymphocyte ratio (CD4+/CD8+) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4+/CD8+ ratio. And the lower level of ß2-microglobulin (<3 mg/L) was associated with a higher CD4+/CD8+ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4+/CD8+ ratio inversion (CD4+/CD8+<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4+/CD8+ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4+/CD8+ inversion patients but did not affect normal CD4+/CD8+ patients. We show that low circulating CD4+/CD8+ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4+/CD8+ ratio less than 1.5.


Assuntos
Relação CD4-CD8 , Macroglobulinemia de Waldenstrom/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/mortalidade , Microglobulina beta-2/análise
13.
Medicine (Baltimore) ; 100(8): e24664, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663076

RESUMO

ABSTRACT: This study aims to evaluate the prognosis and serum immune cells of patients with different pretreatment body mass index (BMI) values. The data of 61 newly diagnosed patients with advanced lung squamous cell carcinoma (LSCC) who received immune checkpoint inhibitors (ICIs) combined with chemotherapy were obtained from the database of Rizhao People's Hospital (Rizhao, Shandong). According to the cutoff value of BMI (23.2 kg/m2), 32 patients had a high BMI and the remaining 29 patients had a low BMI. The effects of different BMIs on the prognosis and serum immune cells of patients were analyzed. The median progression-free survival (PFS) times were 7.72 months in the high BMI group and 4.83 months in the low BMI group [adjusted hazard ratio (HR), 0.23; 95% confidence interval (CI), 0.11-0.48; P < .001]. In terms of the overall survival (OS), the median times of the high BMI group and low BMI group were 18.10 and 13.90 months, respectively (adjusted HR, 0.15; 95% CI, 0.07-0.32; P < .001). After 4 cycles of ICI therapy combined with chemotherapy, the objective response rate was 59.4% for the high BMI group and 20.7% for the low BMI group (P = .002). In addition, the number of serum immune cells in patients with high BMI was significantly higher than that in patients with low BMI (all P < .001). There was a linear relationship between BMI value and the number of serum immune cells (all R2 > 0.7). The current results showed that high BMI is associated with better prognosis in LSCC patients who received ICIs, which may be related to higher levels of serum immune cells.


Assuntos
Antineoplásicos/uso terapêutico , Índice de Massa Corporal , Carcinoma de Células Escamosas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD8-Positivos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Comorbidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Fatores Sexuais , Análise de Sobrevida
14.
Int J Dermatol ; 60(9): 1097-1101, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33611791

RESUMO

BACKGROUND: Lichen planus (LP) is considered to be an immune-mediated disease of a not fully understood etiology. There are scarce data on the immune cells forming the band-like infiltration in cutaneous LP (CLP). The objective of the current study was to investigate the immunohistochemical pattern of cells forming the infiltrate in CLP by assessing the immunoexpression of selected cell lineage markers. METHODS: The immunohistochemical analysis of the expression of CD4, CD8, CD20, CD56, CD68, c-Kit, and Foxp3 was performed in formalin-fixed paraffin-embedded (FFPE) biopsy specimens from 14 cases of CLP and 11 healthy volunteers. RESULTS: The expression of CD4 (P < 0.001), CD8 (P < 0.001), CD68 (P < 0.001), Foxp3 (P < 0.001), CD56 (v = 0.019), and CD20 (P < 0.001) was significantly higher in lesional skin in CLP compared to healthy controls. The ratio of CD4+ to CD8+ cells in the infiltrate was 1.75:1. The expression of Foxp3, CD56, and CD20 was markedly lower than the expression of CD4 and CD8. There was no statistically significant difference in c-Kit expression between CLP lesions and healthy skin (P = 0.57). CONCLUSIONS: We found a wide variety of immune cells in the inflammatory infiltrate in CLP. The expression of CD4, CD8, CD68, Foxp3, CD56, and CD20 was significantly increased in CLP, while the expression of c-Kit was comparable in lesional skin and controls. The presence of various cell populations, including T regulatory cells, NK cells, and B cells, may indicate a complex pathogenesis of CLP.


Assuntos
Linhagem da Célula , Líquen Plano , Dermatopatias , Antígenos CD , Antígenos CD20 , Antígenos de Diferenciação Mielomonocítica , Relação CD4-CD8 , Antígeno CD56 , Fatores de Transcrição Forkhead , Humanos , Proteínas Proto-Oncogênicas c-kit , Pele
15.
Acta Trop ; 217: 105852, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33548205

RESUMO

Clonorchiasis is a zoonotic disease that can result in chronic infection in humans. The causative agent, Clonorchis sinensis (C. sinensis), is believed to primarily induce a Th2 immune response in infected mice. However, few studies have profiled host immune responses to C. sinensis infection during the juvenile phase. In the present study, the dynamics of select cellular responses and cytokine expression profiles during juvenile C. sinensis infection were investigated. The flow cytometry results showed that the CD4+ T cells percentage was significantly decreased between 12 days post-infection (dpi) and 24 dpi in the peripheral blood, and the CD8+ T cells percentage was significantly elevated after 3 dpi. The ratio of CD4+/CD8+ T cells was also significantly decreased after 3 dpi. Furthermore, we observed that the proportion of CD14+ monocyte-macrophages in the peripheral blood was significantly increased between 1 dpi and 12 dpi and peaked at 6 dpi. The percentage of classically activated macrophages (M1) and alternatively activated macrophages (M2) in the liver was significantly increased between 18 dpi and 30 dpi. qRT-PCR results showed that the expression levels of iNOS in the liver were significantly elevated after 3 dpi, and Arg-1 expression was significantly increased beginning at 12 dpi. ELISA results showed that the serum levels of the Th1 cytokines IFN-γ and IL-2 peaked at 6 dpi and decreased thereafter. Furthermore, the Th2 cytokines IL-4 and IL-13 began to be expressed and peaked at 24 dpi and 30 dpi, respectively. In addition, the levels of the Treg cytokines IL-10 and TGF-ß1 were significantly increased beginning at 6 dpi until 30 dpi. In the liver homogenate, the expression of IFN-γ, IL-2, and IL-4 mainly occurred before 6 dpi. IL-13 expression was significantly increased at 30 dpi. IL-10 and TGF-ß1 levels were significantly increased at 12 dpi and 24 dpi, and expression peaked at 24 dpi and 30 dpi, respectively. This study provides a fundamental characterization for the future analysis of host-parasite interactions and immune responses in hosts infected with juvenile C. sinensis.


Assuntos
Clonorquíase/imunologia , Citocinas/imunologia , Imunidade Celular , Macrófagos/imunologia , Animais , Arginase/metabolismo , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Clonorchis sinensis , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Interações Hospedeiro-Parasita , Estágios do Ciclo de Vida , Fígado/parasitologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/metabolismo , Baço/imunologia , Baço/parasitologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
16.
J Acquir Immune Defic Syndr ; 86(2): 219-223, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433124

RESUMO

BACKGROUND: Syphilis has been increasing in the past years, especially among men who have sex with men (MSM). The aim of the study was to assess syphilis prevalence and incidence and changes in CD4 count and viremia in the RV254 cohort of persons living with HIV who initiated antiretroviral therapy during acute HIV infection (AHI) in Bangkok, Thailand. METHODS: From 2009 to 2018, all cohort participants with AHI were tested for syphilis using a qualitative treponemal chemiluminescent microparticle immunoassay and rapid plasma reagin on enrollment, every 24-48 weeks thereafter and when clinically indicated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with incident syphilis. RESULTS: Among 579 participants, the median age was 26 (interquartile range: 22-31) years and 564 (97.4%) were men. Syphilis prevalence at enrollment was 14.3% and incidence was 10.2 cases per 100 person-years. Participants with syphilis were more likely to be MSM (HR 3.68, 95% CI: 1.16 to 11.62), use methamphetamine (HR 2.31, 95% CI: 1.51 to 3.54), and have hepatitis C (HR 2.63, 95% CI: 1.59 to 4.34). HIV RNA >50 copies/mL occurred in 6 (3.9%) participants at incident syphilis diagnosis and in 6 (3.9%) after syphilis treatment. Median CD4 count (cells/mm3) declined from 663 before syphilis to 624 at syphilis diagnosis (P = 0.07), rising again to 660 after syphilis treatment. CONCLUSION: Syphilis was common in the RV254 cohort, inducing a marginal but significant impact on HIV RNA and a temporary decline in CD4. Syphilis screening and behavioral risk reduction counseling should be implemented for MSM with AHI in Thailand.


Assuntos
Contagem de Linfócito CD4 , Relação CD4-CD8 , Infecções por HIV/epidemiologia , Minorias Sexuais e de Gênero , Sífilis/epidemiologia , Carga Viral , Adulto , Estudos de Coortes , Feminino , Hepatite C/epidemiologia , Homossexualidade Masculina , Humanos , Incidência , Masculino , Metanfetamina , Prevalência , Sífilis/diagnóstico , Tailândia/epidemiologia , Adulto Jovem
17.
BMC Microbiol ; 21(1): 11, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407128

RESUMO

BACKGROUND: Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. RESULTS: Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts. CONCLUSIONS: Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Bactérias/classificação , Disbiose/imunologia , Infecções por HIV/tratamento farmacológico , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , Relação CD4-CD8 , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Humanos , Masculino , Metagenômica , Pessoa de Meia-Idade , Filogenia , Resultado do Tratamento
18.
EBioMedicine ; 63: 103175, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33450518

RESUMO

BACKGROUND: During early HIV-1 infection, immunodominant T cell responses to highly variable epitopes lead to the establishment of immune escape virus variants. Here we assessed a type 1-polarized monocyte-derived dendritic cell (MDC1)-based approach to selectively elicit cytotoxic T lymphocyte (CTL) responses against highly conserved and topologically important HIV-1 epitopes in HIV-1-infected individuals from the Thailand RV254/SEARCH 010 cohort who initiated antiretroviral therapy (ART) during early infection (Fiebig stages I-IV). METHODS: Autologous MDC1 were used as antigen presenting cells to induce in vitro CTL responses against HIV-1 Gag, Pol, Env, and Nef as determined by flow cytometry and ELISpot assay. Ultra-conserved or topologically important antigens were respectively identified using the Epigraph tool and a structure-based network analysis approach and compared to overlapping peptides spanning the Gag proteome. FINDINGS: MDC1 presenting either the overlapping Gag, Epigraph, or Network 14-21mer peptide pools consistently activated and expanded HIV-1-specific T cells to epitopes identified at the 9-13mer peptide level. Interestingly, some CTL responses occurred outside known or expected HLA associations, providing evidence of new HLA-associated CTL epitopes. Comparative analyses demonstrated more sequence conservation among Epigraph antigens but a higher magnitude of CTL responses to Network and Gag peptide groups. Importantly, CTL responses against topologically constrained Gag epitopes contained in both the Network and Gag peptide pools were selectively enhanced in the Network pool-initiated cultures. INTERPRETATION: Our study supports the use of MDC1 as a therapeutic strategy to induce and focus CTL responses toward putative fitness-constrained regions of HIV-1 to prevent immune escape and control HIV-1 infection. FUNDING: A full list of the funding sources is detailed in the Acknowledgment section of the manuscript.


Assuntos
Células Dendríticas/imunologia , Epitopos de Linfócito T/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Interações Hospedeiro-Patógeno/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Alelos , Sequência de Aminoácidos , Contagem de Linfócito CD4 , Relação CD4-CD8 , Sequência Conservada , Células Dendríticas/metabolismo , Epitopos de Linfócito T/química , Genótipo , Infecções por HIV/genética , HIV-1/genética , Antígenos HLA/genética , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno/genética , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/imunologia , Linfócitos T Citotóxicos/metabolismo
19.
Exp Neurol ; 336: 113531, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33221395

RESUMO

Stroke is the leading cause of long-term, severe disability worldwide. Immediately after the stroke, endogenous inflammatory processes are upregulated, leading to the local neuroinflammation and the potentiation of brain tissue destruction. The innate immune response is triggered as early as 24 h post-brain ischemia, followed by adaptive immunity activation. Together these immune cells produce many inflammatory mediators, i.e., cytokines, growth factors, and chemokines. Our study examines the immune response components in the early stage of deep brain lacunar infarct in the rat brain, highly relevant to the clinical scenario. The lesion was induced by stereotactic injection of ouabain into the adult rat striatum. Ouabain is a Na/K ATPase pump inhibitor that causes excitotoxicity and brings metabolic and structural changes in the cells leading to focal brain injury. We have shown a surge of neurodegenerative changes in the peri-infarct area in the first days after brain injury. Immunohistochemical analysis revealed early microglial activation and the gradual infiltration of immune cells with a significant increase of CD4+ and CD8+ T lymphocytes in the ipsilateral hemisphere. In our studies, we identified the higher level of pro-inflammatory cytokines, i.e., interleukin-1α, interleukin-1ß, tumor necrosis factor-α, and interferon-γ, but a lower level of anti-inflammatory cytokines, i.e., interleukin-10 and transforming growth factor-ß2 in the injured brain than in normal rats. Concomitantly focal brain injury showed a significant increase in the level of chemokines, i.e., monocyte chemoattractant protein-1 and CC motif chemokine ligand 5 compared to control. Our findings provide new insights into an early inflammatory reaction in our model of the deep-brain lacunar infarct. The results of this study may highlight future stroke immunotherapies for targeting the acute immune response accompanied by the insult.


Assuntos
Infarto Encefálico/complicações , Encefalite/etiologia , Acidente Vascular Cerebral Lacunar/complicações , Animais , Infarto Encefálico/induzido quimicamente , Infarto Encefálico/patologia , Relação CD4-CD8 , Quimiocinas/metabolismo , Citocinas/metabolismo , Encefalite/patologia , Inibidores Enzimáticos , Masculino , Microglia/patologia , Neurogênese , Ouabaína , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Acidente Vascular Cerebral Lacunar/induzido quimicamente , Acidente Vascular Cerebral Lacunar/patologia
20.
Transpl Infect Dis ; 23(2): e13500, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33174284
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