A comprehensive immune repertoire study for patients with pulmonary tuberculosis

Fu, Yingyun; Li, Bo; Li, Yazhen; Wang, Minlian; Yue, Yongjian; Xu, Lan; Li, Shulin; Qing-yun, Huang; Liu, Song; Dai, Yong

doi:10.1002/mgg3.792

Cited by 3 publications

(4 citation statements)

References 16 publications

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“…Remarkably, by sequencing, we revealed that notable disease-severity-associated clones, disease-preferred V β , J β , and V-J junctions exist in OSA and diversity and new clonotypes dramatically increased, suggesting unusual T cell activation and memory for a series of unique MHC-peptides complex exposure. By contrast, a significant decrease in diversity is a common phenomenon that can be found in most previous studies on other conditions, such as cancer, tuberculosis ( Fu et al., 2019 ), pneumonia of COVID-19 ( Chang et al., 2021 ), acute myocardial infarction ( Zhong et al., 2019 ), and subarachnoid hemorrhage ( Kim et al., 2020 ) and corresponds with activation of specific associate TCR clusters to emergent stimuli. Notably, there are several significant factors that can affect the TCR repertoire diversity: (1) aging: the thymus begins to wither after puberty, gradually losing naïve T lymphocytes production, decreasing the ability to respond to neoantigens with age ( Douek et al., 1998 ).…”

Section: Discussionmentioning

confidence: 72%

“…Thus, there was no reliable method for diagnosing and evaluating OSA from peripheral blood before our study. As a novel approach to identifying biomarkers, TCR immune repertoires were previously proved efficient in identifying infectious diseases, autoimmune diseases, carcinoma, and even acute myocardial infarction ( Fu et al., 2019 ; Chang et al., 2021 ; Zhong et al., 2019 ; Kim et al., 2020 ). The complex but unique chronic inflammatory features of OSA, including CIH-induced cell injury and apoptosis products, endothelial function impairment, abnormal metabolomics, colonized microbial flora changes, the impacts of sleep fragmentation, and even early lesion in the cardiovascular system ( Lavie, 2015 ; Khalyfa, Kheirandish-Gozal & Gozal, 2018 ; Humer, Pieh & Brandmayr, 2020 ), can probably contribute to forming a disease-specific repertoire landscape.…”

Section: Discussionmentioning

confidence: 99%

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T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

Zhuo

et al. 2023

PeerJ

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Background Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. Methods We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. Results We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R = 0.603) and smoking (R = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Conclusions Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

Zhuo

et al. 2023

PeerJ

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“…S1-S3). The lowest tertile of TCR surface protein expression (n = 6) was noted to have <0.5% surface TCR protein expression of circulating CD3 + cells, the threshold previously established as a highly expanded clone (10,11). These 6 patients were designated as an "expression-low" cohort for further analyses, whereas the remaining 10 patients were designated as "expression-high."…”

Section: Transgenic Tcr-engineered T Cells Display Strong Persistence...mentioning

confidence: 99%

Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy

et al. 2020

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Transgenic T-cell receptor (TCR) adoptive cell therapies recognizing tumor antigens are associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated using murine stem cell virus (MSCV) γ -retroviral vectors. Analysis of clinical transgenic adoptive cell therapy products in vivo revealed that despite strong persistence of the transgenic TCR DNA sequence over time, its expression was profoundly decreased over time at the RNA and protein levels. Patients with the greatest degrees of expression suppression displayed signifi cant increases in DNA methylation over time within the MSCV promoter region, as well as progressive increases in DNA methylation within the entire MSCV vector over time. These increases in vector methylation occurred independently of its integration site within the host genomes. These results have signifi cant implications for the design of future viral vector gene-engineered adoptive cell transfer therapies. SIGNIFICANCE:Cellular immunotherapies' reliance on retroviral vectors encoding foreign genetic material can be vulnerable to progressive acquisition of DNA methylation and subsequent epigenetic suppression of the transgenic product in TCR adoptive cell therapy. This must be considered in the design of future generations of cellular immunotherapies for cancer. intRoDuctionGenetically engineered adoptive cell therapy (ACT) is revolutionizing cancer treatment, with sustained clinical responses seen in a variety of malignancies. Current approaches utilize retroviral or lentiviral vectors for ex vivo transduction of a patient's T cells to express either a cancer antigen-specifi c T-cell receptor (TCR) or a chimeric antigen receptor (CAR). These reinfused cells then create a focused antitumor response in a variety of cancer subtypes ( 1, 2 ). However, although these Cancer Research.

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“…Significant progress has been made in methods of analyzing aspects of the immune repertoire, providing measures of clonality, diversity, VDJ gene usage, sequence motifs, and network characteristics ( 5 ). These methods, in turn, have led to discoveries of repertoire characteristics in normal aging ( 6 , 7 ), and in diseases such as cancer ( 8 , 9 ), autoimmune disorders ( 9 , 10 ), and infections ( 11 , 12 ). Existing methods have focused on separate analyses of BCR and TCR repertoires, however, and no study to date has attempted to discover existing parallels within an individual’s BCR and TCR repertoires.…”

Section: Introductionmentioning

confidence: 99%

Exploration of shared features of B cell receptor and T cell receptor repertoires reveals distinct clonotype clusters

et al. 2022

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Although B cells and T cells are integral players of the adaptive immune system and act in co-dependent ways to orchestrate immune responses, existing methods to study the immune repertoire have largely focused on separate analyses of B cell receptor (BCR) and T cell receptor (TCR) repertoires. Based on our hypothesis that the shared history of immune exposures and the shared cellular machinery for recombination result in similarities between BCR and TCR repertoires in an individual, we examine any commonalities and interrelationships between BCR and TCR repertoires. We find that the BCR and TCR repertoires have covarying clonal architecture and diversity, and that the pattern of correlations appears to be altered in immune-mediated diseases. Furthermore, hierarchical clustering of public B and T cell clonotypes in both health and disease based on correlation of clonal proportion revealed distinct clusters of B and T cell clonotypes that exhibit increased sequence similarity, share motifs, and have distinct amino acid characteristics. Our findings point to common principles governing memory formation, recombination, and clonal expansion to antigens in B and T cells within an individual. A significant proportion of public BCR and TCR repertoire can be clustered into nonoverlapping and correlated clusters, suggesting a novel way of grouping B and T cell clonotypes.

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A comprehensive immune repertoire study for patients with pulmonary tuberculosis

Cited by 3 publications

References 16 publications

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy

Exploration of shared features of B cell receptor and T cell receptor repertoires reveals distinct clonotype clusters

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