scholarly journals Utilization of Epigenome-wide DNA Methylation for Longitudinal Comparison of White Blood Cell Proportions Across Preeclamptic and Normotensive Pregnancy by Self-Reported Race

2020 ◽  
Author(s):  
Mitali Ray ◽  
Lacey W. Heinsberg ◽  
Yvette P. Conley ◽  
James M. Roberts ◽  
Arun Jeyabalan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cell ◽  
B Cell ◽  
White Blood Cell ◽  
Nk Cell ◽  
Calibration Method ◽  
Small Sample ◽  
Methylation Data ◽  
Longitudinal Comparison ◽  
The Relationship

Objective: We utilized epigenome-wide DNA methylation data to estimate/compare white blood cell (WBC) proportions in plasma across preeclamptic (case) and uncomplicated, normotensive (control) pregnancy. Methods: We previously collected methylation data using Infinium MethylationEPIC Beadchips during the three trimesters in 28 cases and 28 controls (21 Black, 7 White participants/group). We employed the Houseman regression calibration method to estimate and compare neutrophil, monocyte, B cell, NK cell, CD4+ T and CD8+ T cell proportions across pregnancy and between cases and controls. Results: We observed changes in WBC proportions across pregnancy within cases and controls that varied by cell type and race. Neutrophils represented the largest WBC mean proportion in all three trimesters for cases (Mean+/-SD: 67.2+/-9.6% to 74.4+/-12%) and controls (64.2+/-11% to 74.0+/-7.9%). Mean B cell proportions were significantly lower in cases than controls in Trimester 1 (5.25+/-0.02% versus 6.30+/-0.02%, p=0.02). The remaining mean cell proportions did not significantly differ in the overall sample. Stratified analyses revealed race-specific differences. In White participants (n=14): (1) neutrophil proportions were significantly higher in cases in Trimester 1 (p=0.04), but significantly lower in Trimester 2 (p=0.02), (2) B cell proportions were significantly lower in cases in Trimester 1 (p=0.001). No significant differences were detected among Black participants (n=42). Conclusions: Although chronic inflammation characterizes preeclampsia, few studies have investigated WBCs across pregnancy. We report differences between cases and controls across pregnancy. Our findings in a small sample demonstrate the need for additional studies investigating the relationship between race and WBCs in pregnancy, which could provide insight into preeclampsia pathophysiology.

scholarly journals Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction

2018 ◽  
Author(s):  
Meaghan J Jones ◽  
Louie Dinh ◽  
Hamid Reza Razzaghian ◽  
Olivia de Goede ◽  
Julia L MacIsaac ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune System ◽  
Blood Cell ◽  
Cord Blood ◽  
White Blood Cell ◽  
Blood Cells ◽  
Cell Types ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Impact

AbstractBackgroundDNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in DNA methylation of specific white blood cell types between newborn and adult could add insight into the maturation of the immune system. As a consequence of developmental changes, DNA methylation profiles derived from adult white blood cells are poor references for prediction of cord blood cell types from DNA methylation data. We thus examined cell-type specific differences in DNA methylation in leukocyte subsets between cord and adult blood, and assessed the impact of these differences on prediction of cell types in cord blood.ResultsThough all cell types showed differences between cord and adult blood, some specific patterns stood out that reflected how the immune system changes after birth. In cord blood, lymphoid cells showed less variability than in adult, potentially demonstrating their naïve status. In fact, cord CD4 and CD8 T cells were so similar that genetic effects on DNA methylation were greater than cell type effects in our analysis, and CD8 T cell frequencies remained difficult to predict, even after optimizing the library used for cord blood composition estimation. Myeloid cells showed fewer changes between cord and adult and also less variability, with monocytes showing the fewest sites of DNA methylation change between cord and adult. Finally, including nucleated red blood cells in the reference library was necessary for accurate cell type predictions in cord blood.ConclusionChanges in DNA methylation with age were highly cell type specific, and those differences paralleled what is known about the maturation of the postnatal immune system.

scholarly journals Platelet to white blood cell ratio predicts 30-day postoperative infectious complications in patients undergoing radical nephrectomy for renal malignancy

2017 ◽  
Vol 11 (11) ◽  
pp. E414-20 ◽  
Author(s):  
Alaina Garbens ◽  
Christopher J.D. Wallis ◽  
Georg Bjarnason ◽  
Girish S. Kulkarni ◽  
Avery B. Nathens ◽  
...  
Keyword(s):  
Blood Cell ◽  
White Blood Cell ◽  
Radical Nephrectomy ◽  
External Validation ◽  
Infectious Complications ◽  
Bleeding Complications ◽  
Improvement Program ◽  
Cell Ratio ◽  
Increased Risk ◽  
The Relationship

Introduction: We sought to examine the relationship between preoperative platelet to white blood cell ratio (PLT/WBC), a hematological marker of the systemic inflammatory response, and postoperative infectious complications following radical nephrectomy for localized renal cell carcinoma.Methods: We performed a retrospective cohort study of patients treated with radical nephrectomy for localized kidney cancer between January 1, 2005 and December 31, 2014 (n=6235) using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Univariate and multivariate analyses were used to assess the association between PLT/ WBC ratio and 30-day infectious complications, including surgical site infection, urinary tract infection (UTI), pneumonia, and sepsis. Secondarily, we examined major complications and bleeding requiring transfusion.Results: A lower PLT/WBC ratio was associated with an increased risk of sepsis, pneumonia, and UTI rates (p<0.05 for all). Furthermore, there was a significant trend of decreasing rates of sepsis and pneumonia with increasing PLT/WBC ratio across quintiles (p<0.05 for all). On multivariate analysis, patients with the lowest PLT/WBC ratios (Quintile 1) had a two-fold risk of having a postoperative infectious complication compared to patients in the highest quintile (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.42–2.86; p<0.0001). Patients in Quintile 5 had a higher risk of requiring blood transfusion than those in Quintiles 2‒4 (p<0.05 for all).Conclusions: The PLT/WBC ratio represents a widely available and novel index to predict risk of infectious and bleeding complications in patients undergoing radical nephrectomy. External validation is required and the biological underpinning of this phenomenon requires further study

scholarly journals Are methylation beta-values simplex distributed?

2019 ◽  
Author(s):  
Lara Nonell ◽  
Juan R González
Keyword(s):  
Dna Methylation ◽  
Sample Size ◽  
Microarray Data ◽  
Regression Models ◽  
Real Data ◽  
Small Sample ◽  
Beta Regression ◽  
Data Sets ◽  
Methylation Data ◽  
Simplex Distribution

AbstractDNA methylation plays an important role in the development and progression of disease. Beta-values are the standard methylation measures. Different statistical methods have been proposed to assess differences in methylation between conditions. However, most of them do not completely account for the distribution of beta-values. The simplex distribution can accommodate beta-values data. We hypothesize that simplex is a quite flexible distribution which is able to model methylation data.To test our hypothesis, we conducted several analyses using four real data sets obtained from microarrays and sequencing technologies. Standard data distributions were studied and modelled in comparison to the simplex. Besides, some simulations were conducted in different scenarios encompassing several distribution assumptions, regression models and sample sizes. Finally, we compared DNA methylation between females and males in order to benchmark the assessed methodologies under different scenarios.According to the results obtained by the simulations and real data analyses, DNA methylation data are concordant with the simplex distribution in many situations. Simplex regression models work well in small sample size data sets. However, when sample size increases, other models such as the beta regression or even the linear regression can be employed to assess group comparisons and obtain unbiased results. Based on these results, we can provide some practical recommendations when analyzing methylation data: 1) use data sets of at least 10 samples per studied condition for microarray data sets or 30 in NGS data sets, 2) apply a simplex or beta regression model for microarray data, 3) apply a linear model in any other case.

scholarly journals Postprandial alterations in whole-blood DNA methylation are mediated by changes in white blood cell composition

2016 ◽  
Vol 104 (2) ◽  
pp. 518-525 ◽  
Author(s):  
Mathias Rask-Andersen ◽  
Nathalie Bringeland ◽  
Emil K Nilsson ◽  
Marcus Bandstein ◽  
Marcela Olaya Búcaro ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cell ◽  
White Blood Cell ◽  
Whole Blood ◽  
Cell Composition

Incidence of lymphoid neoplasms among atomic bomb survivors by histological subtype: 1950-1994

Blood ◽  
2021 ◽  
Author(s):  
Megumu Fujihara ◽  
Ritsu Sakata ◽  
Noriaki Yoshida ◽  
Kotaro Ozasa ◽  
Dale L Preston ◽  
...  
Keyword(s):  
T Cell ◽  
Radiation Dose ◽  
B Cell ◽  
Dose Response ◽  
Atomic Bomb ◽  
Nk Cell ◽  
Precursor Cell ◽  
Atomic Bomb Survivors ◽  
Lymphoid Neoplasms ◽  
The Relationship

Epidemiological data have provided limited and inconsistent evidence on the relationship between radiation exposure and lymphoid neoplasms. We classified 553 lymphoid neoplasm cases diagnosed between 1950 and 1994 in the Life Span Study (LSS) cohort of atomic bomb survivors into WHO subtypes. Mature B-cell neoplasms represented 58%, mature T-cell and NK-cell neoplasms 20%; precursor cell neoplasms, 5%, and Hodgkin lymphoma, 3%; with the remaining 15% classified as non-Hodgkin lymphoid neoplasms or lymphoid neoplasms, not otherwise specified. We used Poisson regression methods to assess the relationship between radiation exposure and the more common subtypes. As in earlier reports, a significant dose response for non-Hodgkin lymphoid neoplasms as a group was seen for males but not females. However, subtype analyses showed that radiation dose was strongly associated with increased precursor cell neoplasms rates, with an estimated excess relative risk per Gy of 16 (95% Confidence interval: 7.0, &gt;533) at age 50. The current data based primarily of tissue-based diagnoses suggest that the association between radiation dose and lymphoid neoplasms as a group is largely driven by the radiation effect on precursor cell neoplasms while presenting no evidence of a radiation dose response for major categories of mature cell neoplasms, either B- or T-/NK-cell, or more specific disease entities (diffuse large B-cell lymphoma, plasma cell myeloma, adult T-cell leukemia/lymphoma) or Hodgkin lymphoma.

Relationship Between White Blood Cell Count and In-Hospital Outcomes in Acute Coronary Syndrome Patients From the Middle East

Angiology ◽  
2011 ◽  
Vol 63 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Kadhim Sulaiman ◽  
Ibrahim Al-Zakwani ◽  
Prashanth Panduranga ◽  
Jassim Al-Suwaidi ◽  
Alawi A. Alsheikh-Ali ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Middle East ◽  
Blood Cell ◽  
Cardiogenic Shock ◽  
White Blood Cell ◽  
Middle Eastern ◽  
Hospital Outcomes ◽  
Coronary Syndrome ◽  
Wbc Count ◽  
The Relationship

We evaluated the relationship between admission white blood cell (WBC) count and in-hospital outcomes in acute coronary syndrome (ACS) patients from the Middle East. Data were analyzed from 7806 consecutive patients with ACS who were divided into 4 groups (G) according to their WBC count (×109/L; G1: <6.00; G2: 6.00-9.99; G3: 10.00-11.99; G4: ≥12.00). After significant covariate adjustment, those in G4 were 68% more likely to have cardiogenic shock than those in G1 (95% confidence interval [CI]: 1.05-2.68; P = .030) and G2 (odds ratio [OR], 2.02; 95% CI: 1.51-2.71; P < .001). Those in G4 were 2.02 times (95% CI: 1.11-3.67; P = .021) and 65% (95% CI: 1.17-2.32; P = .004) more likely to die in hospital than those in G1 and G2, respectively. Admission WBC count is an independent risk factor for in-hospital cardiogenic shock and mortality, in Middle Eastern patients with ACS. Novel therapeutic agents targeting WBCs in patients with ACS may improve outcomes.

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