scholarly journals Decreased B Lymphocytes Subpopulations Are Associated With Higher Atherosclerotic Risk in Elderly Patients With Moderate-to-severe Chronic Kidney Diseases

2021 ◽  
Author(s):  
Jieshan Lin ◽  
Bin Tang ◽  
Zhanwu Feng ◽  
Wenke Hao ◽  
Wenxue Hu
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Kidney Diseases ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Media Thickness ◽  
Kaplan Meier ◽  
B Cell Subsets

Abstract Aim: Cardiovascular diseases (CVD) are the leading cause of death in patients with chronic kidney disease (CKD), and the risk of CVD increases with reductions in renal function. This study aims to investigate the potential roles of B lymphocyte populations in subclinical atherosclerosis (measured by intima-media thickness, IMT) and prognosis in elderly patients with moderate-to-severe CKD.Methods: In this study, a total of 219 patients (143 moderate-to-severe CKD patients with stage 3-4 and 76 non-CKD controls) were recruited. B cell subsets: B1 cells (CD19+CD5+) and B2 cells (CD19+CD5–) were analyzed by flow cytometry. Intima-media thickness (IMT) was measured by ultrasound. Correlations between the B cell subsets with IMT and clinical outcomes were analyzed.Results: CKD patients showed increased IMT (P=0.006). The level of B, B1 and B2 cells were decreased in CKD patients. Correlation analysis showed that IMT was positively correlated with systolic blood pressure, protein/creatinine ratio and diabetes (P<0.05), and were negatively correlated with B, B1 and B2 lymphocytes (P<0.05). IMT was increased in lower level of B (≤ 0.06 × 109 /L) and B2 cells (≤ 0.05 × 109 /L) (P<0.05). Kaplan-Meier analysis showed that patients with lower level of B, B1 and B2 cells exhibited worse survival (P<0.05).Conclusions: Our results showed that decreased B1 and B2 lymphocytes were correlated with atherosclerosis and worse survival, which indicates that B lymphocytes might involve in atherosclerosis and associated the prognosis of elderly patients with moderate-to-severe CKD.

scholarly journals Decreased B lymphocytes subpopulations are associated with higher atherosclerotic risk in elderly patients with moderate-to-severe chronic kidney diseases

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jieshan Lin ◽  
Bin Tang ◽  
Zhanwu Feng ◽  
Wenke Hao ◽  
Wenxue Hu
Keyword(s):  
Regression Analysis ◽  
B Cells ◽  
Elderly Patients ◽  
B Cell ◽  
B Lymphocytes ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Cox Regression Analysis ◽  
Media Thickness ◽  
B Cell Subsets

Abstract Aim Cardiovascular diseases (CVD) are the leading cause of death in patients with chronic kidney disease (CKD), and the risk of CVD increases with reductions in renal function. This study aims to investigate the potential roles of B lymphocyte populations in subclinical atherosclerosis (measured by intima-media thickness, IMT) and prognosis in elderly patients with moderate-to-severe CKD. Methods In this study, a total of 219 patients (143 moderate-to-severe CKD patients with stage 3–4 and 76 non-CKD controls) were recruited. B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(−) B cells were analyzed by flow cytometry. Intima-media thickness (IMT) was measured by ultrasound. Correlations between the B cell subsets with IMT and clinical outcome was analyzed. Results CKD patients showed increased IMT (P = 0.006). The level of CD19(+)CD5(+) and CD19(+)CD5(−) B cells were decreased in CKD patients. Correlation analysis showed that IMT was positively correlated with systolic blood pressure, protein/creatinine ratio and diabetes (P < 0.05), and were negatively correlated with CD19(+)CD5(+) and CD19(+)CD5(−) B lymphocytes (P < 0.05). Stepwise multiple regression analysis showed that CD19(+)CD5(−) B cells had a significant independent association with IMT (P < 0.05). IMT was increased in lower level of total CD19(+) B cells (≤ 0.06 × 109 /L) and CD19(+)CD5(−) B cells (≤ 0.05 × 109 /L) (P < 0.05). Kaplan-Meier analysis showed that patients with lower levels of CD19(+)CD5(+) and CD19(+)CD5(−) B cells exhibited worse survival (P < 0.05). Cox regression analysis showed that patients with lower CD19(+)CD5(+) and CD19(+)CD5(−) B cells counts have a higher risk of all-cause mortality (P < 0.05). Conclusions Our results showed that decreased CD19(+)CD5(+) and CD19(+)CD5(−) B lymphocytes were correlated with atherosclerosis and worse survival, which indicates that B lymphocytes might involve in atherosclerosis and associated the prognosis of elderly patients with moderate-to-severe CKD.

scholarly journals B-lymphocyte subpopulations in patients with rheumatoid arthritis and the effect of an interleukin-6 receptor inhibitor on them.

2019 ◽  
Vol 56 (6) ◽  
pp. 731-738
Author(s):  
E. V. Gerasimova ◽  
T. V. Popkova ◽  
A. P. Aleksankin ◽  
A. V. Martynova ◽  
E. L. Nasonov
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Interleukin 6 ◽  
B Lymphocyte ◽  
Memory B Cells ◽  
Absolute Count ◽  
The Absolute ◽  
B Cell Subsets ◽  
Receptor Inhibitor

The clinical efficacy and safety of interleukin-6 (IL-6) receptor blockade have been well studied, but the data on the impact of therapeutic inhibition of IL-6 on B cells are scarce and contradictory. Preliminary reports have shown that B cell function and a humoral immune response may be modulated by an IL-6 receptor inhibitor.Objective: to assess the effect of 12-month tocilizumab (TCZ) therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity.Subjects and methods. Examinations were made in 24 active RA patients (20 women and 4 men) (median age, 55 [49; 64] years; disease duration, 72 [24; 108] months; DAS28 5.8 [5.3; 6.3]; the patients were seropositive for rheumatoid factor (RF) (100%) and for anti-cyclic citrullinated peptide antibodies (87.3%). The patients received TCZ 8 mg/kg every 4 weeks. After 12 months of therapy, 54% of patients were categorized as good responders, 46% as moderate responders according to the EULAR response criteria. A control group consisted of 29 volunteers (21 women and 8 men; median age, 58.5 [53.0; 62.0] years). Peripheral blood lymphocytes were immunophenotyped at the time of enrollment and after 12 months. The absolute and relative counts of CD19+B lymphocytes, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgDCD27+), naive (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27) B cells, plasma cells (CD19+СD38+), and plasmablasts (CD19+СD38+++IgD-CD27+CD20-) were estimated using multicolor flow cytometry. Results and discussion. The relative and absolute counts of memory B cells (CD19+CD27+) (1.3 [0.9; 1.7]%, 0015 [0.001; 0.003]•109/l), switched memory B cells (CD19+IgD-CD27+) (6.8 [3.6; 11.6]%, 0.01 [0.005; 0.02]•109/l), and the absolute number of transitional B cells (CD19+CD38++CD10+IgD+CD27-) (0.00009 [0; 0.00028]•109/l) were found to be lower in RA patients than in donors: 2.2 [1.1; 3.0]%, 0.003 [0.001; 0.007]•109/l; 12.8 [9.3; 17.0]%, 0.02 [0.01; 0.04]•109/l; 0.0001 [0; 0.0003]•109/l, respectively (p<0.05 for all cases). After 12 months of TCZ therapy initiation, there were decreases in the relative and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) from 0.15 [0.1; 0.3] to 0.1 [0.01; 0.1]% and from 0.0003 [0.00007; 0.004]•109/l to 0.0001 [0; 0.0003]•109/l, respectively (p<0.05). At the same time, the relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) remained lower in RA patients than in donors: 1.0 [0.7; 1.2] and 2.2 [1.1; 3.0]%; 0.001 [0.006; 0.003]•109/l and 0.003 [0.001; 0.007]•109/l; 3.1 [1.1; 4.2] and 12.8 [9.3; 17.0]%; 0.003 [0.002; 0.006]•109/l and 0.02 [0.01; 0.04]•109/l, respectively (p<0.05 for all cases). Following 12 months of TCZ therapy, the numbers of other B-cell subpopulations were not considerably altered. When included in the study, the patients with RA showed correlations between the absolute count of memory B cells (CD19+CD27+) and the level of C-reactive protein (r=0.50; p<0.05); between the absolute count of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and the level of RF (r=0.41 and r=0.52; p<0.05). There were no correlations of B cell subsets with clinical and laboratory findings after 12 months of TCZ initiation.Conclusion. Immunophenotyping of peripheral blood B lymphocyte subsets showed the lower relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) in RA patients than in healthy donors. The found correlations between the counts of memory B cells and plasmablasts and the values of laboratory parameters in patients with high RA activity may suggest that B lymphocytes are involved in the pathogenesis of RA. There was a decline in plasmablast levels after 12 months of TCZ therapy.

Subclinical atherosclerosis in children and adolescents with congenital heart disease

2020 ◽  
pp. 1-8
Author(s):  
Silvia M. Cardoso ◽  
Michele Honicky ◽  
Yara M. F. Moreno ◽  
Luiz R. A. de Lima ◽  
Matheus A. Pacheco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Congenital Heart Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Clinical Characteristics ◽  
Congenital Heart ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness

Abstract Background: Subclinical atherosclerosis in childhood can be evaluated by carotid intima-media thickness, which is considered a surrogate marker for atherosclerotic disease in adulthood. The aims of this study were to evaluate carotid intima-media thickness and, to investigate associated factors. Methods: Cross-sectional study with children and adolescents with congenital heart disease (CHD). Socio-demographic and clinical characteristics were assessed. Subclinical atherosclerosis was evaluated by carotid intima-media thickness. Cardiovascular risk factors, such as physical activity, screen time, passive smoke, systolic and diastolic blood pressure, waist circumference, dietary intake, lipid parameters, glycaemia, and C-reactive protein, were also assessed. Factors associated with carotid intima-media thickness were analysed using multiple logistic regression. Results: The mean carotid intima-media thickness was 0.518 mm and 46.7% had subclinical atherosclerosis (carotid intima-media thickness ≥ 97th percentile). After adjusting for confounding factors, cyanotic CHD (odds ratio: 0.40; 95% confidence interval: 0.20; 0.78), cardiac surgery (odds ratio: 3.17; 95% confidence interval: 1.35; 7.48), and be hospitalised to treat infections (odds ratio: 1.92; 95% confidence interval: 1.04; 3.54) were associated with subclinical atherosclerosis. Conclusion: Clinical characteristics related to CHD were associated with subclinical atherosclerosis. This finding suggests that the presence of CHD itself is a risk factor for subclinical atherosclerosis. Therefore, the screen and control of modifiable cardiovascular risk factors should be made early and intensively to prevent atherosclerosis.

scholarly journals Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

2021 ◽  
Author(s):  
Eliana Portilla-Fernández ◽  
Shih-Jen Hwang ◽  
Rory Wilson ◽  
Jane Maddock ◽  
W. David Hill ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Association Studies ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

scholarly journals AB0258 CAROTID INTIMA-MEDIA THICKNESS AND SERUM BIOMARKERS IN PARAGUAYAN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1428.2-1428
Author(s):  
V. Valinotti ◽  
A. Paats ◽  
R. Acosta ◽  
L. Roman ◽  
I. Acosta-Colman ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Disease Duration ◽  
Subclinical Atherosclerosis ◽  
High Sensitivity ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Serum Biomarkers ◽  
Carotid Plaques ◽  
Media Thickness ◽  
Hs Crp

Background:The mechanism of increased cardiovascular risk in RA is not well understood and is independent of traditional CV risk factors. Intima-media thickness of the common carotid wall measured by ultrasonogram is a safe and useful biomarker of early stage atherosclerosis that correlates with coronary involvement; and it correlates with severity and duration of disease. Several studies have shown a relationship between inflammation markers, endothelial dysfunction markers, and carotid involvement. (1)Objectives:To determine the presence of inflammation biomarkers and its relationship with subclinical atherosclerosis measured by carotid ultrasound, and with the clinical characteristics in patients with established Rheumatoid Arthritis (RA)Methods:Descriptive, cross sectional, prospective study, in a Paraguayan cohort of patients with RA meeting ACR/EULAR2010 criteria. This study had two phases: the first one, included a standardized questionnaire according to the variables included in the Cardiovascular Risk project (PINV15-0346), from the National Sciences and Technology Council (CONACYT), and physical examination; the second one included laboratory sample collection performed by a specialized laboratory for serum biomarkers measurement for cardiovascular risk prediction (i.e endothelin, alpha-TNF, E-selectin, homocysteine, apolipoprotein, fibrinogen, and high sensitivity-CRP levels) and carotid ultrasound evaluation by a trained specialist, to evaluate subclinical atherosclerosis. Subclinical atherosclerosis was defined as carotid intima-media thickness (CIMT) >0,9mm and/or presence of carotid plaques. All patients signed informed consent. SPSS 23rd version was used for data analysis. Quantitative variables were presented as means and qualitative as frequencies. Chi square test was performed for comparisons between dichotomous variables and t Student for continuous, and p ≤ 0.05 for statistical significance.Results:100 patients were included, 87% were women, mean disease duration 130.9±102.64 months, 77% were RF positive, and 84.4% were ACPA positive, 43.4% had bone erosions, mean ESR-DAS28 was 3,42±1,1; 30% had remission criteria. 39% had extra-articular manifestations.Elevated serum biomarkers were found: fibrinogen >400 mg/dL 88.2%, high sensitivity-CRP (hs-CRP) >5mg/dL 42.9%, endothelin >2 ng/mL 20%, alpha-TNF >15,6 pg/mL 13.1%, E-selectin >79,2 ng/mL 6%. 25.3% had CIMT >0,9 mm and mean CIMT was 0.68±0.25mm. 27.14% had carotid plaques. Patients with CIMT>1mm had higher frequency of family history of arterial hypertension (p=0.006), greater mean disease duration (p=0.0007), hip circumference (p=0.014), blood pressure (SBP p=0.038, DBP p=0.027), HAQ levels (p=0,019) and hs-CRP levels (p=0.013), also lower mean height (p=0,04); while carotid plaques were related to higher homocysteine (p=0.026) and hs-CRP levels (p=0.024).Conclusion:A considerable percentage of patients had subclinical atherosclerosis. Patients with CIMT>0,9mm had a longer disease duration, higher HAQ levels, hip circumference, as well as higher BP. High levels of hs-CRP were more frequently related to the presence of subclinical atherosclerosisReferences:[1]Aday, A. targeting residual inflammatory risk: a shifting paradigm for atherosclerotic disease. Frontiers in cardiovascular medicine. 2019. 6:16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403155/pdf/fcvm-06-00016.pdfDisclosure of Interests:None declared

scholarly journals AB0186 AT WHAT LEVEL SHOULD WE MEASURE INTIMA-MEDIA THICKNESS IN RHEUMATOID ARTHRITIS?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1117.3-1118
Author(s):  
L. Nacef ◽  
H. Ferjani ◽  
H. Riahi ◽  
K. Maatallah ◽  
Y. Mabrouk ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Internal Carotid ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
University Hospital ◽  
External Carotid ◽  
Media Thickness ◽  
The Mean ◽  
The Right ◽  
Score Index

Background:Rheumatoid arthritis (RA) is chronic inflammatory rheumatism characterized by an independent cardiovascular (CV) risk. The screening of carotid intima-media thickness (IMT) in the common carotid artery appears to be a marker of atherosclerosis and is used as a specific tool for CV risk assessment.Objectives:The main of this study was to determine the most associated US sites with CV risk in RA.Methods:The present study is a prospective study conducted on Tunisian RA patients in rheumatology department of Mohamed Kassab University Hospital (March and December 2020). The characteristics of the patients and those of the disease were collected. The measurement of cIMTwas done using high-resolution B-mode carotid US with a Philips machine with the patient in supine position, according to AmericanSociety of Echocardiography guidelines.The carotid bulb below itsbifurcation and the internal and external carotid arteries were evaluated bilaterally with gray scale, spectral and color Doppler ultra-sonography using proprietary software for carotid arterymeasurements.IMT was measured using the two inner layers of the commoncarotid artery and an increased IMT was defined as ≥0.9 mm. The CV risk at 10 years was calculated by the SCORE index.Results:Forty-seven patients were collected, of which 78.7% were women. The mean age was 52.5 ±11.06 years. The rheumatoid factor (RF) was positive in 57.8% of cases, and anti-citrullinated peptide antibodies (ACPA) were positive in 62.2% of cases. RA was erosive in 81.6% of cases. Hypertension (hypertension) was present in 14.9% of patients and diabetes in 12.8% of patients. Nine patients were active smokers. The mean IMT in the left common carotid (LCC) was 0.069 ±0.015, in the left internal carotid (LIC) was 0.069 ±0.015, in the left external carotid (LEC) was 0.060 ±0.023. The mean IMT was 0.068 ±0.01 in the right common carotid (RCC), 0.062 ±0.02 in the right internal carotid (RIC), and 0.060 ±0.016 in the right external carotid (REC). The mean SCORE index of CV risk was 2±2.81 [0-11.6]. CV risk was significantly associated with the IMTs for LIC (p=0.029; r=0.374), LEC (p=0.04; r=0.480), and REC (p=0.016; r=0.408). No association was found between the IMT in the LCC (p=0,361; r=0,162), neither in the RCC (p=0,438; r=0,140) nor the RIC (p=0,670; r=0,077).Conclusion:In our study, IMT is strongly associated with score index, especially in carotid bifurcation. However, IMT measured in common carotid does not reflect a cardiovascular risk at 10-years.References:[1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and Experimental Rheumatology 2018; 36: Clinical E.xperimental.[2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid arthritis. SCANDINAVIAN CARDIOVASCULAR JOURNAL, 2017.[3]Martin I. Wah-Suarez and al, Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control study. Int J Rheum Dis. 2018;1–7.Disclosure of Interests:None declared

Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific genes, surface markers, growth requirements, colonization of the bone marrow, and generation of B lymphocytes in vivo and in vitro

1992 ◽  
Vol 12 (2) ◽  
pp. 518-530
Author(s):  
R Palacios ◽  
J Samaridis
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Stromal Cells ◽  
B Lymphocyte ◽  
Germ Line ◽  
Fetal Liver ◽  
Rag 1 ◽  
B Cell Precursors

We describe here the development and characterization of the FLS4.1 stromal line derived from 15-day fetal liver of BALB/c embryos and defined culture conditions that efficiently support the cloning and long-term growth of nontransformed B-220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B cells (JH-rearranged genes with both light-chain Ig genes in the germ line state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4, rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c-Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the enhanced proliferative response of fetal liver B-220+ B-cell precursors supported by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda 5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell precursors, indicating that the proteins encoded by either gene are not required for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark transcription of the MB-1 gene as one of the earliest molecular events in commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre-B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes; moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do they have rearranged gamma, delta, or beta T-cell antigen receptor genes.

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