scholarly journals Analysis of cell-specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction

2022 ◽  
Author(s):  
Ben Nicholas ◽  
Jane Guo ◽  
Hyun-Hee Lee ◽  
Alistair Bailey ◽  
Rene de Waal Malefyt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Cell ◽  
Nk Cells ◽  
Allergic Asthma ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Peripheral Blood Cell ◽  
Response To Treatment ◽  
Specific Gene ◽  
Severe Allergic Asthma

Asthma is a disease of complex origin and multiple pathologies. There are currently very few biomarkers of proven utility in its diagnosis, management or response to treatment. Recent studies have identified multiple asthma phenotypes following biofluid analysis; however, such findings may be driven by the well-characterised alterations in immune cell populations in asthma. We present a study designed to identify cell type-specific gene signatures of severe allergic asthma in peripheral blood samples. Using transcriptomic profiling of four magnetically purified peripheral blood cell types, we identify significant gene expression changes in monocytes and NK cells but not T lymphocytes in severe asthmatics. Pathway analysis indicates dysfunction of immune cell regulation and bacterial suppression in the NK cells. These gene expression changes may be useful on their own as prognostic peripheral blood cell markers of severe asthma, but also may indicate novel cell pathways for therapeutic intervention.

scholarly journals Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures

Theranostics ◽  
2016 ◽  
Vol 6 (11) ◽  
pp. 1792-1809 ◽  
Author(s):  
Sunil M. Kurian ◽  
Marta Novais ◽  
Thomas Whisenant ◽  
Terri Gelbart ◽  
Joel N. Buxbaum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Cell ◽  
Transthyretin Amyloidosis ◽  
Male And Female ◽  
Cell Gene Expression ◽  
Female Specific ◽  
Cell Gene

scholarly journals Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

2019 ◽  
Author(s):  
Chang Ik Yoon ◽  
So Eun Park ◽  
Yoon Jin Cha ◽  
Soong June Bae ◽  
Chi Hwan Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Laboratory Data ◽  
Peripheral Blood Cell ◽  
Cell Mediated Immunity ◽  
Breast Cancer Patients ◽  
Cell Counts ◽  
Blood Cell Counts

AbstractTumor-infiltrating lymphocytes (TILs) might be associated with host-cell mediated immunity, which could be partly reflected by peripheral blood cell counts. We aimed to investigate whether peripheral blood cell counts are associated with TILs in breast cancer. Between August 2016 and July 2018, we evaluated the percentage of stromal TILs in breast cancer patients who underwent primary surgery, using the standardized methodology proposed by the international TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors having high TIL levels (≥ 50%). Peripheral blood cell counts including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC) and neutrophil-to-lymphocyte ratio (NLR) was obtained from pretreatment laboratory data. Of the 684 patients, 99 (17.2%) had LPBC, and 478 (82.8%) had non-LBPC. In a comparison of 3 markers of peripheral blood counts, LPBC had a significantly lower mean ANC than non-LPBC (3,330 vs. 3,660; P=0.004), but the other means were not different. Decreasing ANC was an independent clinical factor in predicting LPBC (OR: 0.736, 95% CI: 0.591-0.917; P=0.004). Low peripheral ANC might be linked with LPBC, supporting the hypothesis that systemic immune cell counts might be associated with the tumor-immune microenvironment.

scholarly journals Acute Radiation Syndrome-related gene expression in irradiated peripheral blood cell populations

2021 ◽  
pp. 1-32
Author(s):  
Patrick Ostheim ◽  
Alan Don Mallawaratchy ◽  
Thomas Müller ◽  
Simone Schüle ◽  
Cornelius Hermann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Cell ◽  
Acute Radiation ◽  
Cell Populations ◽  
Related Gene ◽  
Acute Radiation Syndrome

scholarly journals 34 Selective infiltration of Antibody-Dependent Cellular Cytoxicity (ADCC) mediating immune cells in response to treatment in a human tumor histo-culture platform

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A40-A40
Author(s):  
Satish Sankaran ◽  
Nandini Pal Basak ◽  
Sindhu Govindan ◽  
BV Prakash ◽  
BV Manjula ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Nk Cell ◽  
Granzyme B ◽  
Human Tumor ◽  
Neutrophil Infiltration ◽  
Fold Change ◽  
Response To Treatment

BackgroundA 3D histo-culture platform provides a near native Tumor immune Micro-Environment (TiME), making it best suited for evaluating response to immunotherapy drugs. Farcast™ TiME is a human 3D tumor histo-culture platform that preserves TiME and maintains functional fidelity of intra-tumoral immune cells (IIC). In this study we investigated the utility of this platform in demonstrating treatment induced Antibody-Dependent Cellular Cytotoxicity (ADCC) mechanism driven by IICs alone versus co-culture with autologous peripheral blood immune cells.MethodsHead and neck squamous cell carcinoma tissue samples (n=5) along with matched blood from consented patients were used in this study. All Peripheral Blood Nucleated Cells (PBNCs) including lymphocytes, monocytes, NK cells and neutrophils were isolated and stained with a tracking dye to distinguish them from IICs. Tumor tissues were processed to generate explants, treated with 184 µg/ml Cetuximab (anti-EGFR) or vehicle control, and cultured with or without PBNCs for 72 hrs. Response was evaluated using flow cytometry and cytokine release assay.ResultsAmount of infiltrated autologous PBNCs showed a strong negative correlation (R2=0.98) with the amount of IICs in the absence of drug treatment. The proportions of infiltrated immune cell sub-populations were similar to the composition of PBNCs added in culture. Cetuximab treatment, however, led to enhanced infiltration of the effector cells for ADCC driven tumor killing, namely NK cells, macrophages, neutrophils, and cytotoxic T cells (CTLs). Notably the unique infiltration pattern of effector cell populations observed in each sample was reflected in the secretion of specific cytokine/chemokines associated with that cell population. NK cell increase (fold change: 1.6 ± 0.8) was observed in all samples with a concomitant increase in MCP-1 secretion (fold change: 1.7 ± 0.9). Granzyme-B expressing NK cells increased (>1.7 fold) in a subset of samples. Samples showing increase in neutrophil infiltration exhibited increased MMP9 secretion, involved in neutrophil infiltration via stromal remodeling. Sample with highest increase in infiltration of CD16+ Monocyte/Macrophages (>2.4 fold) showed maximum increase in Granzyme-B secretion with respect to the untreated arm. Increase in fold secretion (>1.4) of CXCL9/CXCL10 was associated with the sample that showed highest fold increase of Granzyme-B expressing CTL in comparison to untreated arm. IICs alone were not sufficient in eliciting optimal ADCC response.ConclusionsThe study demonstrated ADCC response in the explant/PBNC co-culture platform leading to specific infiltration of effector sub-populations. FarcastTM TiME thus provides a unique platform to explore for heterologous adoptive cell and CAR-T therapies that involve immune cell infiltration.Ethics ApprovalAll samples included in the study were approved by institutional review boards of the centers providing the samples.

scholarly journals Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Multiple Testing ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

Abstract 3259: Leukocyte Subset Specific Gene Expression In Acute Stroke Patients

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Mateusz G Adamski ◽  
Yan Li ◽  
Hua Yu ◽  
Erin Wagner ◽  
Sareen Amarjeet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Stroke ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Specific Gene ◽  
Related Gene ◽  
Stroke Patients ◽  
Leukocyte Subset ◽  
Control Subjects

Background: Alterations in gene expression in the peripheral blood of patients with acute stroke have been demonstrated using microarray technology. Whole blood and peripheral blood mononuclear cells (PBMCs) were used in prior studies in which panels of genes diagnostic for stroke were developed. We aimed to determine the cellular sources of alterations in gene expression by studying individual leukocyte subsets. Methods: The expression of four genes previously found to be upregulated in ischemic and hemorrhagic stroke (IL1R2, S100A9, ETS2 and F5) was measured in four leukocyte subsets: CD14+ monocytes, CD4+ T cell lymphocytes, CD20+ B cell lymphocytes and PBMCs. These four genes had been reported in at least two of the previously published stroke-related gene panels. Peripheral blood was obtained from six acute stroke patients (all <48 hours from symptom onset) and 6 age, race and sex matched control subjects. Leukocytes were separated from whole blood using density gradient centrifugation and column magnetic bead cell sorting. The purity of separated leukocyte subsets exceeded 90% and was verified with flow cytometry. Messenger RNA was isolated from each leukocyte subset and analyzed by two step RT PCR and qPCR. The expression of the four stroke-related genes was compared to the expression of a housekeeping gene (GAPDH). The relative expression of individual genes and of the 4 gene panel within cellular subsets was compared between stroke patients and control subjects. Results: Individually, IL1R2 and S100A9 were significantly over-expressed in stroke patients with a 10 fold increase for IL1R2 in PBMCs (p<0.05) and a 3 fold increase for S100A9 in the CD4+ T and CD20+ B lymphocyte subsets (p<0.05). When analyzed as a panel of four genes the expression of IL1R2, S100A9, ETS2 and F5 was significantly higher in both the CD4+ T lymphocytes (p<0.05) and CD20+ B lymphocytes (p<0.05) of stroke patients but not in the monocytes or the PBMCs. Conclusion: These results show the potential diagnostic value of selected genes from panels previously found in microarray studies in stroke patients. They also emphasize the value of panel analysis over that of single gene expression and the potential cellular specificity of alterations in gene expression. Analysis of whole blood and PBMCs alone may not reflect important dynamic changes in stroke-related gene expression.

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