scholarly journals Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes

2021 ◽  
Vol 16 (1) ◽  
pp. 884-898
Author(s):  
Ruiqiang Weng ◽  
Sudong Liu ◽  
Xiaodong Gu ◽  
Zhixiong Zhong
Keyword(s):  
Type 2 Diabetes ◽  
B Cell ◽  
Clonal Diversity ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Amino Acid Sequences ◽  
Stent Restenosis ◽  
Overlap Rate ◽  
In Stent Restenosis

Abstract Type 2 diabetes mellitus (T2DM) is known as a risk factor for coronary in-stent restenosis (ISR) in patients with coronary artery disease (CAD). Evidence suggests that B cells play a functional role in the progression of atherosclerotic lesions. However, the B cell receptor (BCR) repertoire in patients with ISR remains unclear. This study aims to profile the BCR repertoire in patients with coronary ISR/T2DM. A total of 21 CAD patients with or without ISR/T2DM were enrolled. PBMCs were isolated and examined for BCR repertoire profiles using DNA-seq. Our results showed that the diversity of amino acid sequences in ISR DM patients was higher than that in ISR −DM patients. The frequencies of 21 V/J paired genes differed between ISR DM and −ISR DM patients, while frequencies of 5 V/J paired genes differed between ISR DM and ISR −DM. The −ISR −DM group presented the highest clonotype overlap rate, while ISR DM patients presented the lowest overlap rate. Our study presented the BCR repertoires in patients with ISR/T2DM. The data suggested different BCR signatures between patients with ISR and T2DM. Further analysis of BCR profiles would enhance understanding of ISR.

scholarly journals Clonal Diversity of the B cell Receptor Repertoire in Patients with Coronary in-Stent Restenosis and Diabetes Mellitus

2020 ◽  
Author(s):  
Ruiqiang Weng ◽  
Sudong Liu ◽  
Xiaodong Gu ◽  
Zhixiong Zhong
Keyword(s):  
Diabetes Mellitus ◽  
B Cells ◽  
B Cell ◽  
Clonal Diversity ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Amino Acid Sequences ◽  
Common Amino Acid ◽  
Stent Restenosis ◽  
In Stent Restenosis

Abstract Background Coronary artery disease patients with diabetes mellitus may have a higher risk for clinical and angiographic restenosis. Evidence has suggested that B cells play a functional role in the progression of atherosclerotic lesions. The purpose of this study was to investigate the clonal diversity of the B cell receptor (BCR) repertoire in patients with coronary in-stent restenosis (ISR) and diabetes mellitus.Methods In the present study, we had enrolled 21 patients with ISR and DM or not and collected the peripheral blood mononuclear cell. The DNA was extrated and then we performed DNA-seq analysis to character the B-cell receptor profiles (BCR) of CAD patients with or without ISR. The BCR diversity and the overlap was evaluate by the bioinformatics base on the DNA-seq data.Result Seq-data showed that the diversity of amino acids was altered in patients with ISR. Specifically, 6 V gene segments as well as 41 V/J pairs exhibited different frequencies in patients with ISR, with the altered common amino acid sequences reaching 0.1–1.01% in ISR patients.Conclusion The present findings suggest that B cells may play a role in the occurrence of ISR and that further analysis of BCR profiles would enhance understanding of ISR.

scholarly journals 67 B-cell receptor heavy chain repertoire profiling using an augmented transcriptome

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A72-A72
Author(s):  
Eric Levy ◽  
Pamela Milani ◽  
Gabor Bartha ◽  
Charles Abbott ◽  
Robert Power ◽  
...  
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Solid Tumor ◽  
Clonal Diversity ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Ffpe Sample ◽  
Response To Treatment ◽  
Ffpe Tumor ◽  
Ffpe Samples

BackgroundComprehensive profiling of the tumor and tumor microenvironment (TME) is a critical tool for furthering our understanding of tumor progression and response to treatment, including immunotherapies. To address this challenge, we developed an augmented, immuno-oncology-optimized exome/transcriptome platform, ImmunoID NeXTTM, which provides a more comprehensive view of the tumor and TME from limited FFPE tumor biopsies. We have recently added the ability to profile the B-cell receptor (BCR) heavy chain. Here, we show that ImmunoID NeXT is now able to accurately and reproducibly profile abundant B-cell clones and provide information on the diversity of B-cells in tumor samples.MethodsWe analyzed multiple replicates of PBMCs to examine the reproducibility of BCR sequence identification using ImmunoID NeXT. Utilizing a standalone BCR sequencing approach, we further evaluated the concordance of top clones to those identified by ImmunoID NeXT. In addition, we analyzed the reproducibility of BCR sequences in patient-derived FFPE samples. Finally, we used ImmunoID NeXT to profile the B-cell clonal diversity across over 500 solid tumor samples.ResultsReproducibility in PBMC samples was very high, with abundances of clones shared between replicates being very concordant (R2>0.92, R2>0.86, and R2>0.97 for IgG, IgM, and IgA, respectively). When comparing to a standalone BCR sequencing method that profiles IgM and IgG, we observed highly concordant abundances (R2>0.72 and R2>0.82 in IgM and IgG, respectively), as well as strong overlaps of top clones. When comparing subsequent curls of a tumor FFPE sample, we also achieved a high concordance of clonal abundances (R2>0.92, R2>0.93, and R2>0.76 for IgG, IgM, and IgA, respectively). Finally, we observed differences in clonal diversity of B-cell repertoires across over 500 solid tumor samples.ConclusionsWe demonstrate that ImmunoID NeXT can be used to reproducibly, sensitively, and accurately profile high-abundance BCR heavy chain clones, including coverage of all major isotypes. In addition, we show how ImmunoID NeXT can profile the diversity of the BCR repertoire across a variety of tumor samples. Combined with the platform’s TCR profiling capabilities, ImmunoID NeXT can provide insight into the diversity of the immune repertoire, contributing to its ability to provide comprehensive analysis of both the tumor and TME from a single FFPE sample.

scholarly journals Visit-to-Visit HbA1c Variability is Associated with In-Stent Restenosis in Patients with Type 2 Diabetes after Percutaneous Coronary Intervention

2020 ◽  
Author(s):  
Chen Die Yang ◽  
Ying Shen ◽  
Lin Lu ◽  
Zhen Kun Yang ◽  
Jian Hu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Stent Implantation ◽  
Coronary Intervention ◽  
Diabetic Patients ◽  
Stent Restenosis ◽  
Percutaneous Coronary ◽  
The Mean ◽  
In Stent Restenosis

Abstract Background: Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation.Methods: We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR.Results: From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8±1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P=0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9±16.8%, 0.42±0.88 mm and 1.66±0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P<0.001), and this trend was more prominent in patients with optimal glycemic control (HbA1c≤7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI:1.14~7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings. Conclusions: This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation.Trial registration: Trials number, NCT02089360; registered on March 17,2014.

scholarly journals Revisiting the Coreceptor Function of Complement Receptor Type 2 (CR2, CD21); Coengagement With the B-Cell Receptor Inhibits the Activation, Proliferation, and Antibody Production of Human B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Kristóf G. Kovács ◽  
Bernadett Mácsik-Valent ◽  
János Matkó ◽  
Zsuzsa Bajtay ◽  
Anna Erdei
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antibody Production ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Type ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Human B Cells

The positive coreceptor function of complement receptor type 2 [CR2 (CD21)] on B cells is generally accepted, although its role in the enhancement of antibody production had only been proven in mice. The importance of this phenomenon prompted reinvestigation of the functional consequences of coclustering CD21 and the B cell receptor (BCR) on primary human cells. We found that, at non-stimulatory concentrations of anti-IgG/A/M, coclustering the BCR and CR2 enhanced the Ca2+ response, while activation marker expression, cytokine production, proliferation, and antibody production were all inhibited upon the coengagement of CR2 and BCR on human B cells. Thus, the “textbook dogma” claiming that C3d acts as an adjuvant to enhance humoral immunity is relevant only to mice and not to humans.

scholarly journals Bioabsorbable vascular endoproteases for the treatment of patients with coronary heart disease and type 2 diabetes mellitus

2017 ◽  
Vol 95 (9) ◽  
pp. 824-828
Author(s):  
Z. Kh. Shugushev ◽  
Daniil A. Maksimkin ◽  
Yu. S. Vorob’eva ◽  
A. G. Chepurnoy ◽  
G. I. Veretnik ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Arteries ◽  
Long Term Outcomes ◽  
Stent Restenosis ◽  
Major Cardiovascular Events ◽  
In Stent Restenosis

Aim. To evaluate efficiency of endovascular intervention in patients with type 2 diabetes mellitus with the use of bioabsorbable vascular endoproteases and everolimus-coated stents. Material and methods. A total of 143 patients were initially selected for the study of whom 125 were randomized into 2 groups, one including 57 patients with implanted bioabsorbable vascular endoproteases, the other comprised of 68 patients treated with the use of everolimus-coated stents. Inclusion criteria: primary lesion of coronary arteries, stable angina of effort (II-III FC), myocardial ischemia (>10%) confirmed in functional tests, compensated and subcompensated DM2, stenosis of middle and distal segments of the main coronary arteries (≥70%) diagnosed by digital angiography. Exclusion criteria: the target artery not more than 4 mm in diameter, acute coronary syndrome, excess vascular tortuosity, marked calcinosis of coronary arteries, bifurcation lesion, left coronary trunk lesion, history of myocardial revascularization. Criteria for the assessment of immediate outcomes: frequency of major cardiovascular events (death, myocardial infarction, emergency secondary intervention). Criteria for the assessment of long-term outcomes: frequency of major cardiovascular events (death, myocardial infarction, secondary intervention), frequency of in-scaffold/in-stent restenosis or stent thrombosis. Results of biobsorbable scaffold implantation were controlled using optical coherence tomography in the end of surgery and during 12 month during follow-up. Results. A total of 63 bioabsorbable vascular endoprostheses and 102 everolimus-coated stents were implanted to patients of groups 1 and 2 respectively. Mean diameter of the endoprostheses was 2.88±0.06 and 2.68±0.12 mm respectively (р>0,05). The intervention was regarded as technically successful in 100% cases. The overall frequency of major cardiovascular complications during hospitalization in patients of groups 1 and 2 was 3.5 and 2.94% respectively. Long-term outcomes could be estimated in 41 patients of group 1 and 52 ones in group 2. All patients survived for 12 months. The frequency of non-fatal MI was 4.9 and 3.8% in groups 1 and 2 respectively (р>0,05), the cause being progression of atherosclerosis in other arteries. Frequency of in-stent restenosis was 2.4 and 1.9% (р>0,05). Cases of late stent thrombosis were absent whereas coherence tomography revealed severe intravascular volume depletion to 0.14±0.19 and 0.12±0,23 mm in groups 1 and 2 respectively (р>0,05). Conclusion. Bioabsorbable endoprostheses implanted to patients with coronary heart disease and type 2 diabetes mellitus and stenosis of middle and distal segments of the main coronary arteries within 12 months after surgery proved as efficient and safe as everolimus-coated stents.

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