Search

Your search keyword '"Renren Ouyang"' showing total 16 results
Start Over Author "Renren Ouyang"
16 results on '"Renren Ouyang"'

1. Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer

Author

Yun Wang, Rujia Chen, Zhenzhou Guo, Wei Wei, Ting Wang, Renren Ouyang, Xu Yuan, Yutong Xing, Feng Wang, Shiji Wu, and Hongyan Hou

Subjects
Lung cancer, PD-1, PD-L1, CD4 + T cells, Treg Cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) antibodies, have achieved breakthrough results in improving long-term survival rates in lung cancer. Although high levels of PD-L1 expression and tumor mutational burden have emerged as pivotal biomarkers, not all patients derive lasting benefits, and resistance to immune checkpoint blockade remains a prevalent issue. Comprehending the immunological intricacies of lung cancer is crucial for uncovering the mechanisms that govern responses and resistance to immunomodulatory treatments. This study aimed to explore the potential of peripheral immune markers in predicting treatment efficiency among lung cancer patients undergoing PD-1/PD-L1 checkpoint inhibitors. Methods This study enrolled 71 lung cancer patients undergoing PD-1/PD-L1 inhibitor therapy and 20 healthy controls. Immune cell subsets (CD4 + T cells, CD8 + T cells, B cells, NK cells, and NKT cells), phenotypic analysis of T cells and B cells, and PMA/Ionomycin-stimulated lymphocyte function assay were conducted. Results Lung cancer patients exhibited significant alterations in immune cell subsets, notably an increased percentage of Treg cells. Post-treatment, there were substantial increases in absolute numbers of CD3 + T cells, CD8 + T cells, and NKT cells, along with heightened HLA-DR expression on CD3 + T and CD8 + T cells. Comparison between complete remission and non-complete remission (NCR) groups showed higher Treg cell percentages and HLA-DR + CD4 + T cells in the NCR group. Conclusion The study findings suggest potential predictive roles for immune cell subsets and phenotypes, particularly Treg cells, HLA-DR + CD4 + T cells, and naïve CD4 + T cells, in evaluating short-term PD-1/PD-L1 therapy efficacy for lung cancer patients. These insights offer valuable prospects for personalized treatment strategies and underscore the importance of immune profiling in lung cancer immunotherapy.

Published
2024
Full Text
View/download PDF

2. Novel multiclass classification machine learning approach for the early-stage classification of systemic autoimmune rheumatic diseases

Author

Feng Wang, Ting Wang, Wei Wei, Yun Wang, Xu Yuan, Renren Ouyang, Rujia Chen, Hongyan Hou, and Shiji Wu

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objective Systemic autoimmune rheumatic diseases (SARDs) encompass a diverse group of complex conditions with overlapping clinical features, making accurate diagnosis challenging. This study aims to develop a multiclass machine learning (ML) model for early-stage SARDs classification using accessible laboratory indicators.Methods A total of 925 SARDs patients were included, categorised into SLE, Sjögren’s syndrome (SS) and inflammatory myositis (IM). Clinical characteristics and laboratory markers were collected and nine key indicators, including anti-dsDNA, anti-SS-A60, anti-Sm/nRNP, antichromatin, anti-dsDNA (indirect immunofluorescence assay), haemoglobin (Hb), platelet, neutrophil percentage and cytoplasmic patterns (AC-19, AC-20), were selected for model building. Various ML algorithms were used to construct a tripartite classification ML model.Results Patients were divided into two cohorts, cohort 1 was used to construct a tripartite classification model. Among models assessed, the random forest (RF) model demonstrated superior performance in distinguishing SLE, IM and SS (with area under curve=0.953, 0.903 and 0.836; accuracy= 0.892, 0.869 and 0.857; sensitivity= 0.890, 0.868 and 0.795; specificity= 0.910, 0.836 and 0.748; positive predictive value=0.922, 0.727 and 0.663; and negative predictive value= 0.854, 0.915 and 0.879). The RF model excelled in classifying SLE (precision=0.930, recall=0.985, F1 score=0.957). For IM and SS, RF model outcomes were (precision=0.793, 0.950; recall=0.920, 0.679; F1 score=0.852, 0.792). Cohort 2 served as an external validation set, achieving an overall accuracy of 87.3%. Individual classification performances for SLE, SS and IM were excellent, with precision, recall and F1 scores specified. SHAP analysis highlighted significant contributions from antibody profiles.Conclusion This pioneering multiclass ML model, using basic laboratory indicators, enhances clinical feasibility and demonstrates promising potential for SARDs classification. The collaboration of clinical expertise and ML offers a nuanced approach to SARDs classification, with potential for enhanced patient care.

Published
2024
Full Text
View/download PDF

3. Dynamic changes in peripheral blood lymphocyte subset counts and functions in patients with diffuse large B cell lymphoma during chemotherapy

Author

Hongyan Hou, Ying Luo, Guoxing Tang, Bo Zhang, Renren Ouyang, Ting Wang, Min Huang, Shiji Wu, Dengju Li, and Feng Wang

Subjects
Diffuse large B cell lymphoma, Lymphocyte subsets, CD4+ T cells, CD8+ T cells, NK cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Background This study aimed to analyze the lymphocyte subsets, their activities and their dynamic changes during immunochemotherapy in patients newly diagnosed with diffuse large B cell lymphoma (DLBCL). Methods Patients with DLBCL (n = 33) were included in the present study. Their peripheral lymphocyte subsets, phenotypes and functions were detected using flow cytometry. The dynamic results of lymphocyte activities were available for 18 patients. Results Compared with healthy controls (HCs), the counts of CD3+, CD4+, and CD8+ T cells as well as those NK cells decreased in patients newly diagnosed with DLBCL, mainly attributed to patients with high risk of prognosis assessed by International Prognostic Index (IPI) score. Lymphocyte counts didn’t present significant difference between high risk (IPI scores 3–5) and low risk patients (IPI scores 0–2), but CD4+ T cells and CD8+ T cells expressed higher levels of CD28 and HLA-DR, respectively, in patients with IPI score ranging from 3 to 5. Patients at high risk harbored higher percentage of regulatory T cells (Tregs), and their CD4+ and CD8+ T cells produced lower levels of IFN-γ, reflecting an impaired cellular immune response. The dynamic changes of lymphocyte numbers and functions during treatment were further investigated. Total counts of CD3+, CD4+, CD8+ T and NK cells progressively decreased because of the cytotoxicity of chemotherapy and then gradually recovered after six cycles treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). The functions of CD4+ and CD8+ T cells recovered by the end of two cycles R-CHOP treatment, although NK cell function was not significantly affected throughout treatment. These results suggest that the counts and functions of lymphocytes are significantly decreased in patients with DLBCL, particularly those of CD4+ and CD8+ T cells. Conclusions The absolute counts and functions of CD4+, CD8+ T cells, which were significantly lower in patients with DLBCL, gradually recovered after effective treatment. Therefore, combined detection of T cell counts and functions are critically important for administering effective personalized immunotherapy as well as for identifying new prognostic markers or DLBCL.

Published
2021
Full Text
View/download PDF

4. Diagnostic utility of pleural fluid T-SPOT and interferon-gamma for tuberculous pleurisy: A two-center prospective cohort study in China

Author

Ying Luo, Feng Yan, Ying Xue, Liyan Mao, Qun Lin, Guoxing Tang, Huijuan Song, Shiji Wu, Renren Ouyang, Xu Yuan, Weiyong Liu, Jing Yu, Yu Zhou, Hongyan Hou, Xuejuan Sun, Feng Wang, and Ziyong Sun

Subjects
PF T-SPOT, IFN-γ, Diagnostic model, Tuberculous pleurisy, Infectious and parasitic diseases, RC109-216
Abstract

Background: Early and accurate diagnosis of tuberculous pleurisy (TP) remains a challenge. The aim of the present study is to evaluate the performance of the pleural fluid (PF) T-SPOT and interferon-gamma (IFN-γ) for TP diagnosis in high tuberculosis (TB) burden settings. Methods: In total, 214 and 217 subjects suspected of TP were prospectively enrolled in the Wuhan (training) cohort and Changchun (validation) cohort, respectively. All patients were examined with PF T-SPOT, IFN-γ, and other traditional tests simultaneously. Results: The receiver-operating characteristic (ROC) curve analysis showed that the area under the curve (AUC), sensitivity, and specificity of TB-specific antigen (TBAg) spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in PF T-SPOT assay) for TP diagnosis were 0.972, 92.86%, and 92.16%, respectively, with a cutoff value of 35 in the Wuhan cohort. Meanwhile, when a threshold value of 95 ng/mL was set, the AUC, sensitivity, and specificity of IFN-γ to diagnose TP were 0.951, 86.61%, and 90.20%, respectively. Moreover, the diagnostic model based on the combination of TBAg SFC and IFN-γ showed an AUC of 0.983 for differentiating TP from non-TP, with 95.54% sensitivity and 95.10% specificity when a cutoff value of 0.32 was used in the Wuhan cohort. Excellent diagnostic accuracy was also observed in the Changchun cohort. When applying the cutoff value obtained from the Wuhan cohort, the AUC, sensitivity, and specificity of the diagnostic model were 0.995, 95.08%, and 97.89%, respectively. Conclusions: The performance of PF T-SPOT was comparable to IFN-γ in diagnosing TP. However, using the diagnostic model established by the combination of these two assays can achieve a more accurate diagnosis of TP.

Published
2020
Full Text
View/download PDF

5. HLA-DR Expression Level in CD8+ T Cells Correlates With the Severity of Children With Acute Infectious Mononucleosis

Author

Yun Wang, Ying Luo, Guoxing Tang, Renren Ouyang, Minxia Zhang, Yuhuan Jiang, Ting Wang, Xiwen Zhang, Botao Yin, Jin Huang, Wei Wei, Min Huang, Feng Wang, Shiji Wu, and Hongyan Hou

Subjects
EBV, infectious mononucleosis, CD8+ T cells, CD4+ T cells, HLA-DR+ CD8+ T cells, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundThis study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM).MethodsTwenty-eight pediatric patients with IM aged 3–8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected.ResultsThe percentages and absolute numbers of CD3+ and CD8+ T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4+ and CD8+ T cells were decreased but with increased percentages of memory CD4+ and CD8+ T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αβ, and inhibitory receptors PD-1, TIGIT in CD8+ T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4+ and CD8+ T cells after stimulation with PMA/ionomycin in vitro. Multivariate analysis revealed that the percentage of HLA-DR+ CD8+ T cells was an independent prognostic marker for IM. The percentage of HLA-DR+ CD8+ T cells was significantly correlated with high viral load and abnormal liver function results.ConclusionRobust expansion and upregulation of HLA-DR in CD8+ T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+ CD8+ T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.

Published
2021
Full Text
View/download PDF

6. Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Author

Ying Luo, Ying Xue, Liyan Mao, Qun Lin, Guoxing Tang, Huijuan Song, Wei Liu, Shutao Tong, Hongyan Hou, Min Huang, Renren Ouyang, Feng Wang, and Ziyong Sun

Subjects
activation phenotype, HLA-DR, Mycobacterium tuberculosis, discrimination, active tuberculosis, latent tuberculosis infection, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundRapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.MethodsParticipants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.ResultsA total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity.ConclusionsWe demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.

Published
2021
Full Text
View/download PDF

7. Combination of Blood Routine Examination and T-SPOT.TB Assay for Distinguishing Between Active Tuberculosis and Latent Tuberculosis Infection

Author

Ying Luo, Guoxing Tang, Xu Yuan, Qun Lin, Liyan Mao, Huijuan Song, Ying Xue, Shiji Wu, Renren Ouyang, Hongyan Hou, Feng Wang, and Ziyong Sun

Subjects
active tuberculosis, latent tuberculosis infection, differential diagnosis, diagnostic model, blood routine examination, T-SPOT.TB, Microbiology, QR1-502
Abstract

BackgroundDistinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging.MethodsBetween 2013 and 2019, 2,059 (1,097 ATB and 962 LTBI) and another 883 (372 ATB and 511 LTBI) participants were recruited based on positive T-SPOT.TB (T-SPOT) results from Qiaokou (training) and Caidian (validation) cohorts, respectively. Blood routine examination (BRE) was performed simultaneously. Diagnostic model was established according to multivariate logistic regression.ResultsSignificant differences were observed in all indicators of BRE and T-SPOT assay between ATB and LTBI. Diagnostic model built on BRE showed area under the curve (AUC) of 0.846 and 0.850 for discriminating ATB from LTBI in the training and validation cohorts, respectively. Meanwhile, TB-specific antigens spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in T-SPOT assay) produced lower AUC of 0.775 and 0.800 in the training and validation cohorts, respectively. The diagnostic model based on combination of BRE and T-SPOT showed an AUC of 0.909 for differentiating ATB from LTBI, with 78.03% sensitivity and 90.23% specificity when a cutoff value of 0.587 was used in the training cohort. Application of the model to the validation cohort showed similar performance. The AUC, sensitivity, and specificity were 0.910, 78.23%, and 90.02%, respectively. Furthermore, we also assessed the performance of our model in differentiating ATB from LTBI with lung lesions. Receiver operating characteristic analysis showed that the AUC of established model was 0.885, while a threshold of 0.587 yield a sensitivity of 78.03% and a specificity of 85.69%, respectively.ConclusionsThe diagnostic model based on combination of BRE and T-SPOT could provide a reliable differentiation between ATB and LTBI.

Published
2021
Full Text
View/download PDF

9. HLA-DR Expression Level in CD8+ T Cells Correlates With the Severity of Children With Acute Infectious Mononucleosis

Author

Shiji Wu, Ting Wang, Jin Huang, Renren Ouyang, Yun Wang, Wei Wei, Minxia Zhang, Min Huang, Botao Yin, Feng Wang, Hongyan Hou, Xiwen Zhang, Guoxing Tang, Ying Luo, and Yuhuan Jiang

Subjects
biology, business.industry, medicine.medical_treatment, CD3, Immunology, infectious mononucleosis, RC581-607, CD8+ T cells, CD4+ T cells, Cytokine, Immune system, TIGIT, EBV, HLA-DR+ CD8+ T cells, HLA-DR, medicine, biology.protein, Immunology and Allergy, Cytotoxic T cell, Cytokine secretion, Immunologic diseases. Allergy, business, CD8
Abstract

BackgroundThis study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM).MethodsTwenty-eight pediatric patients with IM aged 3–8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected.ResultsThe percentages and absolute numbers of CD3+and CD8+T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4+and CD8+T cells were decreased but with increased percentages of memory CD4+and CD8+T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αβ, and inhibitory receptors PD-1, TIGIT in CD8+T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4+and CD8+T cells after stimulation with PMA/ionomycinin vitro. Multivariate analysis revealed that the percentage of HLA-DR+CD8+T cells was an independent prognostic marker for IM. The percentage of HLA-DR+CD8+T cells was significantly correlated with high viral load and abnormal liver function results.ConclusionRobust expansion and upregulation of HLA-DR in CD8+T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+CD8+T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.

Published
2021

10. Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Author

Shutao Tong, Ying Xue, Ziyong Sun, Guoxing Tang, Min Huang, Renren Ouyang, Feng Wang, Qun Lin, Ying Luo, Hongyan Hou, Huijuan Song, Liyan Mao, and Wei Liu

Subjects
medicine.medical_treatment, latent tuberculosis infection, Immunology, CD38, Mycobacterium tuberculosis, activation phenotype, HLA-DR, Immunology and Allergy, Medicine, IL-2 receptor, biology, Latent tuberculosis, active tuberculosis, business.industry, RC581-607, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Cytokine, Cohort, Biomarker (medicine), Immunologic diseases. Allergy, business, discrimination
Abstract

BackgroundRapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.MethodsParticipants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.ResultsA total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity.ConclusionsWe demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.

Published
2021

11. Combination of Blood Routine Examination and T-SPOT.TB Assay for Distinguishing Between Active Tuberculosis and Latent Tuberculosis Infection

Author

Feng Wang, Ying Luo, Liyan Mao, Ziyong Sun, Xu Yuan, Ying Xue, Hongyan Hou, Guoxing Tang, Huijuan Song, Shiji Wu, Renren Ouyang, and Qun Lin

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, latent tuberculosis infection, Immunology, Logistic regression, Sensitivity and Specificity, Microbiology, Gastroenterology, 03 medical and health sciences, Cellular and Infection Microbiology, 0302 clinical medicine, Latent Tuberculosis, blood routine examination, Internal medicine, Diagnostic model, differential diagnosis, medicine, Humans, Tuberculosis, 030212 general & internal medicine, T-SPOT.TB, Original Research, Antigens, Bacterial, active tuberculosis, Latent tuberculosis, Receiver operating characteristic analysis, business.industry, Area under the curve, Mycobacterium tuberculosis, bacterial infections and mycoses, medicine.disease, Active tuberculosis, Training cohort, QR1-502, 030104 developmental biology, Infectious Diseases, diagnostic model, business
Abstract

BackgroundDistinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging.MethodsBetween 2013 and 2019, 2,059 (1,097 ATB and 962 LTBI) and another 883 (372 ATB and 511 LTBI) participants were recruited based on positive T-SPOT.TB (T-SPOT) results from Qiaokou (training) and Caidian (validation) cohorts, respectively. Blood routine examination (BRE) was performed simultaneously. Diagnostic model was established according to multivariate logistic regression.ResultsSignificant differences were observed in all indicators of BRE and T-SPOT assay between ATB and LTBI. Diagnostic model built on BRE showed area under the curve (AUC) of 0.846 and 0.850 for discriminating ATB from LTBI in the training and validation cohorts, respectively. Meanwhile, TB-specific antigens spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in T-SPOT assay) produced lower AUC of 0.775 and 0.800 in the training and validation cohorts, respectively. The diagnostic model based on combination of BRE and T-SPOT showed an AUC of 0.909 for differentiating ATB from LTBI, with 78.03% sensitivity and 90.23% specificity when a cutoff value of 0.587 was used in the training cohort. Application of the model to the validation cohort showed similar performance. The AUC, sensitivity, and specificity were 0.910, 78.23%, and 90.02%, respectively. Furthermore, we also assessed the performance of our model in differentiating ATB from LTBI with lung lesions. Receiver operating characteristic analysis showed that the AUC of established model was 0.885, while a threshold of 0.587 yield a sensitivity of 78.03% and a specificity of 85.69%, respectively.ConclusionsThe diagnostic model based on combination of BRE and T-SPOT could provide a reliable differentiation between ATB and LTBI.

Published
2021

12. Clinical value of tumor-associated antigens and autoantibody panel combination detection in the early diagnostic of lung cancer

Author

Min Huang, Yun Wang, Jin Huang, Bo Zhang, Renren Ouyang, Feng Wang, Botao Yin, Hongyan Hou, Ting Wang, Wei Wei, Shiji Wu, and Minxia Zhang

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Antigen, Internal medicine, Genetics, medicine, Humans, Lung cancer, CYFRA 21-1, Pathological, 030304 developmental biology, Autoantibodies, Retrospective Studies, 0303 health sciences, biology, business.industry, Autoantibody, General Medicine, Middle Aged, medicine.disease, Epithelial Cell Adhesion Molecule, 030220 oncology & carcinogenesis, biology.protein, Adenocarcinoma, Female, Antibody, business
Abstract

BACKGROUND: This study aimed to investigate the efficiency of combining tumor-associated antigens (TAAs) and autoantibodies in the diagnosis of lung cancer. METHODS: The serum levels of TAAs and seven autoantibodies (7-AABs) were detected from patients with lung cancer, benign lung disease and healthy controls. The performance of a new panel by combing TAAs and 7-AABs was evaluated for the early diagnosis of lung cancer. RESULTS: The positive rate of 7-AABs was higher than the single detection of antibody. The positive rate of the combined detection of 7-AABs in lung cancer group (30.2%) was significantly higher than that of healthy controls (16.8%), but had no statistical difference compared with that of benign lung disease group (20.8%). The positive rate of 7-AABs showed a tendency to increase in lung cancer patients with higher tumor-node-metastasis (TNM) stages. For the pathological subtype analysis, the positive rate of 7-AABs was higher in patients with squamous cell carcinoma and small cell lung cancer than that of adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 211 (CYFRA 21-1) were significantly higher than that of benign lung disease and healthy control groups. An optimal model was established (including 7-AABs, CEA and CYFRA21-1) to distinguish lung cancer from control groups. The performance of this model was superior than that of single markers, with a sensitivity of 52.26% and specificity of 77.46% in the training group. Further assessment was studied in another validation group, with a sensitivity of 44.02% and specificity of 83%. CONCLUSIONS: The diagnostic performance was enhanced by combining 7-AABs, CEA and CYFRA21-1, which has critical value for the screening and early detection of lung cancer.

Published
2021

13. Activation Phenotype of

Author

Ying, Luo, Ying, Xue, Liyan, Mao, Qun, Lin, Guoxing, Tang, Huijuan, Song, Wei, Liu, Shutao, Tong, Hongyan, Hou, Min, Huang, Renren, Ouyang, Feng, Wang, and Ziyong, Sun

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, latent tuberculosis infection, Immunology, Lymphocyte Activation, Immunophenotyping, Diagnosis, Differential, Young Adult, activation phenotype, Latent Tuberculosis, Humans, Tuberculosis, Aged, Original Research, active tuberculosis, HLA-DR, Mycobacterium tuberculosis, Middle Aged, bacterial infections and mycoses, ROC Curve, Cytokines, Female, Disease Susceptibility, Biomarkers, discrimination
Abstract

Background Rapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue. Methods Participants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation. Results A total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity. Conclusions We demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.

Published
2021

14. Dynamic changes in peripheral blood lymphocyte subset counts and functions in patients with diffuse large B cell lymphoma during chemotherapy

Author

Dengju Li, Min Huang, Shiji Wu, Ting Wang, Guoxing Tang, Bo Zhang, Hongyan Hou, Renren Ouyang, Feng Wang, and Ying Luo

Subjects
Cancer Research, Lymphocyte, T cell, Lymphocyte subsets, Diffuse large B cell lymphoma, NK cells, CD8+ T cells, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, hemic and lymphatic diseases, Genetics, medicine, Cytotoxic T cell, RC254-282, QH573-671, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, CD28, medicine.disease, CD4+ T cells, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Peripheral blood lymphocyte, Immunology, Primary Research, Cytology, business, Diffuse large B-cell lymphoma, CD8, 030215 immunology
Abstract

Background This study aimed to analyze the lymphocyte subsets, their activities and their dynamic changes during immunochemotherapy in patients newly diagnosed with diffuse large B cell lymphoma (DLBCL). Methods Patients with DLBCL (n = 33) were included in the present study. Their peripheral lymphocyte subsets, phenotypes and functions were detected using flow cytometry. The dynamic results of lymphocyte activities were available for 18 patients. Results Compared with healthy controls (HCs), the counts of CD3+, CD4+, and CD8+ T cells as well as those NK cells decreased in patients newly diagnosed with DLBCL, mainly attributed to patients with high risk of prognosis assessed by International Prognostic Index (IPI) score. Lymphocyte counts didn’t present significant difference between high risk (IPI scores 3–5) and low risk patients (IPI scores 0–2), but CD4+ T cells and CD8+ T cells expressed higher levels of CD28 and HLA-DR, respectively, in patients with IPI score ranging from 3 to 5. Patients at high risk harbored higher percentage of regulatory T cells (Tregs), and their CD4+ and CD8+ T cells produced lower levels of IFN-γ, reflecting an impaired cellular immune response. The dynamic changes of lymphocyte numbers and functions during treatment were further investigated. Total counts of CD3+, CD4+, CD8+ T and NK cells progressively decreased because of the cytotoxicity of chemotherapy and then gradually recovered after six cycles treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). The functions of CD4+ and CD8+ T cells recovered by the end of two cycles R-CHOP treatment, although NK cell function was not significantly affected throughout treatment. These results suggest that the counts and functions of lymphocytes are significantly decreased in patients with DLBCL, particularly those of CD4+ and CD8+ T cells. Conclusions The absolute counts and functions of CD4+, CD8+ T cells, which were significantly lower in patients with DLBCL, gradually recovered after effective treatment. Therefore, combined detection of T cell counts and functions are critically important for administering effective personalized immunotherapy as well as for identifying new prognostic markers or DLBCL.

Published
2021

15. Combination of mean spot sizes of ESAT-6 spot-forming cells and modified tuberculosis-specific antigen/phytohemagglutinin ratio of T-SPOT.TB assay in distinguishing between active tuberculosis and latent tuberculosis infection

Author

Xu Yuan, Renren Ouyang, Ying Luo, Shiji Wu, Ying Xue, Liyan Mao, Weiyong Liu, Hongyan Hou, Ziyong Sun, Jing Yu, Feng Wang, Yu Zhou, Guoxing Tang, and Qun Lin

Subjects
0301 basic medicine, Microbiology (medical), Tuberculosis, 030106 microbiology, Sensitivity and Specificity, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Antigen, Bacterial Proteins, Latent Tuberculosis, medicine, Humans, 030212 general & internal medicine, Phytohemagglutinins, T-SPOT.TB, Phytohaemagglutinin, Antigens, Bacterial, Latent tuberculosis, medicine.diagnostic_test, biology, business.industry, Area under the curve, Mycobacterium tuberculosis, bacterial infections and mycoses, medicine.disease, Infectious Diseases, Immunology, ESAT-6, biology.protein, business
Abstract

Summary Objectives Distinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging. Methods The modified T-SPOT.TB assay was performed in 499 participants (243 ATB and 256 LTBI) and another 322 participants (162 ATB and 160 LTBI) who were diagnosed in Qiaokou (training) and Caidian (validation) cohort respectively. Results The mean spot sizes (MSS) of early secreted antigenic target 6 (ESAT-6) spot-forming cells (SFC) of T-SPOT.TB assay in ATB patients was significantly higher than that in LTBI individuals. 1.0 × 105 was the optimal number of cells added to phytohaemagglutinin (PHA) well for obtaining more accurate TB-specific antigen to phytohaemagglutinin (TBAg/PHA) ratio. The area under the curve of the diagnostic model by combination of ESAT-6 SFC MSS and modified TBAg/PHA ratio in distinguishing ATB from LTBI was 0.959 in training cohort, with a sensitivity of 90.12% and a specificity of 91.02% when a cutoff value of 0.46 was used. This diagnostic model showed similar performance in the validation cohort. The area under the curve, sensitivity, and specificity were 0.962, 93.21%, and 90.00%, respectively. Further flow cytometry analysis showed that ESAT-6 stimulation induced a significantly higher mean fluorescence intensity of IFN-γ+ cells in lymphocytes compared with culture filtrate protein 10 (CFP-10) stimulation. In contrast, CFP-10 stimulation induced a significantly higher percentage of IFN-γ+ cells in lymphocytes compared with ESAT-6 stimulation. Conclusions The combination of the MSS of ESAT-6 SFC and the modified TBAg/PHA ratio of T-SPOT.TB assay showed great value in discriminating ATB from LTBI.

Published
2020

16. Evaluation of the automated indirect immunofluorescence test for anti-dsDNA antibodies

Author

Minxia Zhang, Botao Yin, Min Huang, Feng Wang, Wei Wei, Jin Huang, Renren Ouyang, and Shiji Wu

Subjects
0301 basic medicine, Clinical Biochemistry, Immunofluorescence Microscopy, Biochemistry, Sensitivity and Specificity, 03 medical and health sciences, Automation, 0302 clinical medicine, Medicine, Humans, Lupus Erythematosus, Systemic, Fluorescent Antibody Technique, Indirect, Indirect immunofluorescence, biology, business.industry, Anti-dsDNA antibodies, Biochemistry (medical), Antibody titer, General Medicine, Reference Standards, Specific antibody, 030104 developmental biology, Microscopy, Fluorescence, 030220 oncology & carcinogenesis, Antibodies, Antinuclear, Case-Control Studies, Immunology, biology.protein, lipids (amino acids, peptides, and proteins), Antibody, business
Abstract

Background Anti-dsDNA antibody is a specific antibody in systemic lupus erythematosus (SLE). Indirect immunofluorescence test (IIFT) is a highly specific method in detecting anti-dsDNA antibody. The application of automated system has gained better consistency than manual operation. This study detected anti-dsDNA antibodies using EUROPattern Computer-aided immunofluorescence microscopy (EPA), and evaluated the performance of the automated system. Methods The sera of 96 patients with suspected SLE and 102 control patients were examined using IIFT. The consistency between the EPA and manual reading was analyzed. Results Analysis of 198 samples showed that the overall consistency of the negative/positive results between the EPA and manual reading was 94.95%. Based on the manual reading results, the sensitivity and specificity of EPA were 95.70% and 94.29%, respectively. The analysis of 57 samples with non-specific fluorescence showed that the overall consistency of the negative/positive results was 96.49%. The analysis of the antibody titer of 89 positive samples showed that the consistency between the EPA and manual reading was 97.75%. Conclusion EPA was consistent with the manual reading with regard to qualitative reading and antibody titer. With low-exposure function, EPA could read samples with non-specific fluorescence. EPA was superior to manual reading in automation and standardization.

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results