scholarly journals ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongguo Yu ◽  
Jiayu Zhang ◽  
Youguang Zhuo ◽  
Xu Hong ◽  
Jie Ye ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Femoral Head ◽  
Immune Cells ◽  
Early Stage ◽  
Diagnostic Markers ◽  
Memory B Cells ◽  
Qrt Pcr ◽  
Significant Difference ◽  
The Relationship

BackgroundThe diagnosis for steroid-induced osteonecrosis of the femoral head (SONFH) is hard to achieve at the early stage, which results in patients receiving ineffective treatment options and a poor prognosis for most cases. The present study aimed to find potential diagnostic markers of SONFH and analyze the effect exerted by infiltration of immune cells in this pathology.Materials and MethodsR software was adopted for identifying differentially expressed genes (DEGs) and conducting functional investigation based on the microarray dataset. Then we combined SVM-RFE, WGCNA, LASSO logistic regression, and random forest (RF) algorithms for screening the diagnostic markers of SONFH and further verification by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. CIBERSORT was then adopted for assessing the infiltration of immune cells and the relationship of infiltration-related immune cells and diagnostic markers.ResultsWe identified 383 DEGs overall. This study found ARG2, MAP4K5, and TSTA3 (AUC = 0.980) to be diagnostic markers of SONFH. The results of qRT-PCR showed a statistically significant difference in all markers. Analysis of infiltration of immune cells indicated that neutrophils, activated dendritic cells and memory B cells were likely to show the relationship with SONFH occurrence and progress. Additionally, all diagnostic markers had different degrees of correlation with T cell follicular helper, neutrophils, memory B cells, and activated dendritic cells.ConclusionARG2, MAP4K5, and TSTA3 are potential diagnostic genes for SONFH, and infiltration of immune cells may critically impact SONFH occurrence and progression.

scholarly journals Prognostic Value of Complement Properdin in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Alessandro Mangogna ◽  
Praveen M. Varghese ◽  
Chiara Agostinis ◽  
Salman H. Alrokayan ◽  
Haseeb A. Khan ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Prognostic Marker ◽  
Immune Cells ◽  
Complement System ◽  
Alternative Pathway ◽  
Complement Protein ◽  
Significant Difference ◽  
The Complement System

The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or malignant cells. Properdin is the only known positive regulator of the alternative pathway. In addition, properdin promotes the phagocytic uptake of apoptotic T cells by macrophages and dendritic cells without activating the complement system, thus, establishing its ability to recognize “altered-self”. Dysregulation of properdin has been implicated in substantial tissue damage in the host, and in some cases, chronic unresolved inflammation. A corollary of this may be the development of cancer. Hence, to establish a correlation between properdin presence/levels in normal and cancer tissues, we performed bioinformatics analysis, using Oncomine and UALCAN. Survival analyses were performed using UALCAN and PROGgeneV2 to assess if properdin can serve as a potential prognostic marker for human lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LIHC), cervical squamous cell carcinoma (CESC), and pancreatic adenocarcinoma (PAAD). We also analyzed levels of tumor-infiltrating immune cells using TIMER, a tool for characterizing immune cell composition in cancers. We found that in LUAD and LIHC, there was a lower expression of properdin in the tumors compared to normal tissues, while no significant difference was observed in CESC and PAAD. Survival analysis demonstrated a positive association between properdin mRNA expression and overall survival in all 4 types of cancers. TIMER analysis revealed that properdin expression correlated negatively with tumor purity and positively with levels of infiltrating B cells, cytotoxic CD8+ T cells, CD4+ helper T cells, macrophages, neutrophils and dendritic cells in LUAD, CESC and PAAD, and with levels of B cells, CD8+ T cells and dendritic cells in LIHC. Immunohistochemical analysis revealed that infiltrating immune cells were the most likely source of properdin in the tumor microenvironment. Thus, complement protein properdin shows promise as a prognostic marker in cancer and warrants further study.

The roles of immune cells in atherosclerotic calcification

Vascular ◽  
2021 ◽  
pp. 170853812110327
Author(s):  
Jingsong Cao ◽  
Xuyu Zu ◽  
Jianghua Liu
Keyword(s):  
B Cells ◽  
Immune Cells ◽  
Cardiovascular Events ◽  
Th2 Cells ◽  
Regulatory B Cells ◽  
T Helper ◽  
Relationship Of ◽  
The Relationship ◽  
Helper Type

Atherosclerosis is the leading cause of acute cardiovascular events, and vascular calcification is an important pathological phenomenon in atherosclerosis. Recently, many studies have shown that immune cells are closely associated with the development of atherosclerosis and calcification, but there are many conflicting viewpoints because of immune system complications, such as the pro-atherosclerotic and atheroprotective effects of regulatory B cells (Bregs), T helper type 2 (Th2) cells and T helper type 17 (Th17) cells. In this review, we summarize the studies on the roles of immune cells, especially lymphocytes and macrophages, in atherosclerotic calcification. Furthermore, we prepared graphs showing the relationship between T cells, B cells and macrophages and atherosclerotic calcification. Finally, we highlight some potential issues that are closely associated with the function of immune cells in atherosclerotic calcification. Based on current research results, this review summarizes the relationship between immune cells and atherosclerotic calcification, and it will be beneficial to understand the relationship of immune cells and atherosclerotic calcification.

scholarly journals Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome

2018 ◽  
Vol 219 (3) ◽  
pp. 420-428 ◽  
Author(s):  
Hyun Ah Yoon ◽  
Antonio Nakouzi ◽  
Christina C Chang ◽  
Mark H Kuniholm ◽  
Leandro J Carreño ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Memory B Cells ◽  
Hiv Viral Load ◽  
Immunodeficiency Virus ◽  
Plasma Antibody ◽  
Inflammatory Syndrome ◽  
The Relationship ◽  
Cd4 T Cell Count

AbstractBackgroundInitiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated.MethodsWe compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS.ResultsPrior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells.DiscussionAntibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.

scholarly journals Characterization of B-cell Receptor Heavy Chain Complementarity-determining Region 3 Repertoire Based on the Differences of Symbiotic Microorganisms in the Gut of Mice

2021 ◽  
Author(s):  
Jun Li ◽  
Yurong Pan ◽  
Qingqing Ma ◽  
Long Ma ◽  
Bin Shi ◽  
...  
Keyword(s):  
Small Intestine ◽  
B Cells ◽  
B Cell ◽  
Heavy Chain ◽  
Intestinal Microflora ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Positive Effects ◽  
Significant Difference

Abstract Background Colonization of gut microorganism is related to maturation of B cells in peripheral immune organs. This study aims to investigate the effect of intestinal microflora in Germ-free (GF), Specific Pathogen-free (SPF) and Clean (CL) BALB/C mice to small intestine total B-cell and memory B-cell receptor (BCR) complementary-determining region 3 (CDR3) repertoire. Results The composition and characteristics of intestinal microflora were analyzed by 16S rDNA sequencing. Genomic DNA extracted from small intestine tissue and memory B-cells of GF, SPF and CL mice were conducted via high-throughput DNA sequencing methods. As expected, significant differences of gut microflora diversity were observed in the three mice groups. CL group showed the most diversity, followed by SPF group, and GF group had the lowest diversity. Moreover, anormogenesis of intestinal lymphoid tissue were observed in GF mice. Diversity of the BCR heavy chain CDR3 repertoire in memory B cells were significant difference among three groups, but not in total B cells. The nucleotide polymorphism, usage frequency of gene segments (V, D, J, V–J gene segments) and amino acid of total B cells and memory B cells CDR3 were comparable among three mice groups, and there was significant difference between CL and GF mice groups. Conclusions The results of this study advocate that the colonization of intestinal microorganisms affect the diversity of B cells CDR3 repertoire. Elucidating mechanism of microbiome participated in the function of intestinal mucosal immune system may have positive effects on human health, and it requires further investigation.

scholarly journals Immune Cell Landscape in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yang Yang ◽  
Wei He ◽  
Zi-rui Wang ◽  
Yu-jiao Wang ◽  
Lan-lan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Univariate Analysis ◽  
Molecular Therapy ◽  
Expression Level ◽  
Regulatory Factors ◽  
Normal Tissues ◽  
The Relationship

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

Phenotypic Analysis of CD19+ Subsets In Monoclonal Gammopathy Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4998-4998
Author(s):  
Lucie Kovarova ◽  
Pavla Zarbochova ◽  
Tamara Varmuzova ◽  
Ivana Buresova ◽  
Karthick Raja Muthu Raja ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Healthy Volunteers ◽  
Peripheral Blood ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Phenotypic Analysis ◽  
Transitional B Cells ◽  
Significant Difference

Abstract Abstract 4998 Background. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder which can eventually progress into malignant multiple myeloma (MM). Plasma cells (PCs) are the terminal stadium of B cells differentiation, but it is still unclear which population is the source of pathological PCs with malignant transformation and which population is involved in and may give rise to clonogenic myeloma stem cells. Aims. Phenotypic analysis of CD19+ cell subpopulations in monoclonal gammopathy patients and healthy volunteers to asses their frequency and to find differences on cellular level. Methods. Total of 38 samples was analyzed (16 newly diagnosed untreated MM patients, 12 untreated MGUS persons and 10 healthy donors). CD19+ cells were analyzed for surface expression of CD24, CD27, CD38, and IgD by 5-colors immunophenotyping. Subpopulations of pre-plasma cells consist of transitional B cells (CD24+CD38+), naïve B cells (CD38-IgD+), activated B cells (CD38+IgD+), preGC B cells (CD38++IgD+) and memory B cells (CD38-/+IgD-). These were evaluated in whole lysed peripheral blood together with circulating plasmablast/plasma cells (CD38++IgD-). Bone marrow of MGUS and MM patients was analyzed for number of transitional, immature and memory B cells. Results. Flow cytometric analysis shown no statistical difference when compared number of transitional B cells (1.8%; 3.0% and 1.2%) and activated B cells (54.6%; 62.1% and 45.5%) in peripheral blood of healthy volunteers, MGUS and MM patients, respectively. There was found lower number of circulating plasmablast/plasma cells in peripheral blood of healthy volunteers than in MGUS (1.0% vs. 1.7%; p<0.01), but there was no statistically significant difference for MM (1.7%) when compared to others. The highest number of peripheral naive B cells was found in healthy volunteers (21.4%; p<0.001) and the highest number of peripheral memory B cells was found in MM patients (32.9%; p<0.01) when compared to other groups. There was found also higher number of peripheral preGC B cells in MGUS and MM patients (2.7% vs. 1.6% vs. 1.3%; p<0.05) than in healthy volunteers, respectively. Although numbers of transitional and immature B cells in bone marrow were different for MGUS and MM, the only statistically significant difference was found in number of memory B cells (25.4% for MGUS vs. 11.9% for MM; p<0.01). Summary/Conclusions. Our result showed differences in CD19+ subsets when compared peripheral blood of healthy volunteers and monoclonal gammopathy patients as well as in bone marrow of monoclonal gammopathy group. These differences could be a sign of ongoing changes in B cells of monoclonal gammopathy patients. Further analysis will be also focused on changes at DNA level to confirm clonality of selected subpopulations and to find possible myeloma stem cells source. Supported by GACR 301/09/P457, GACR GAP304/10/1395, MSMT LC06027, MSM0021622434, IGA 10408-3, IGA 10406-3. Disclosures: Hajek: Janssen-Cilag: Honoraria; Celgene: Honoraria; Merck, Sharp, and Dohme: Honoraria.

Biologic meshes in cancer patients: A double-edged sword—Differences in production of IL6 and IL12 caused by acellular dermal matrices in human immune cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3064-3064
Author(s):  
Maria Margarete Guenthner-Biller ◽  
Sabine Enders ◽  
Julia Knabl ◽  
Verena Engelstaedter ◽  
Peter Duewell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Statistical Difference ◽  
Wilcoxon Test ◽  
Dermal Matrices ◽  
Acellular Dermal

3064 Background: Acellular dermal matrices (ADM) have been used in different fields of surgery for almost 20 years. In 2005 Breuing et al first described its use in breast cancer patients. It is assumed that it is safe to use in an oncologic setting, but data from controlled studies are still missing. Because of its lack of cells ADM are considered not to cause an immune reaction. With increasing knowledge about the importance of immunology in breast cancer more information about ADM on different immune cell populations is needed. IL6 and IL12 are two central cytokines and key regulators of immune supression and activation. Methods: Strattice (ST; LifeCell) CollaMend (CM; Bard Davol), Biodesign (BD; Cook Biotec) as well as TiLoop a synthetic mesh (TL; pfm medical) were used in this study. We isolated myeloid dendritic cells (MDC), untouched plasmacytoid dendritic cells (PDC), naïve B-cells and CD8+ T-cells using the MACS System and co-cultered them with the biologic meshes or TL. For positive controls, we used CpG ODN 2216 3 µg/ml and LPS in a concentration of 100 ng/ml. Cytokine concentration of IL12p70 and IL6 were determined after seven days by using sandwich Elisa sets. Statistical significance was determined by the nonparametric Friedman-Test. The single hypothesis was calculated with a paired Wilcoxon Test. Results: There was a highly significant difference between the different ADM and TL in the immunologic response. The statistical difference for IL 6 was p= 0.0006131 for B cells and p= 0.00418 for T cells between TL and ADM. ST also caused significantly more IL6 than CM and BD. We found similar differences in IL 12 with p= 0.00194 for B cells and p= 0.003636 in T cells in regard to the difference between TL and ADM. For IL 12 there was no statistical difference between the ADM. We didn´t see any significant differences in the cytokine profile between the various ADM/TL in the MDC and PDC subpopulations. Conclusions: Despite the assumed lack of immune answer to ADM, immune cells reacted in our study with significantly different cytokine profiles. These findings can have implications regarding the activation or suppression of effector cells in a cancer patient.

B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy

2010 ◽  
Vol 69 (12) ◽  
pp. 2181-2188 ◽  
Author(s):  
Inmaculada de la Torre ◽  
Rita A Moura ◽  
Maria J Leandro ◽  
Jonathan Edwards ◽  
Geraldine Cambridge
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Receptor Expression ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
B Cell Activating Factor ◽  
Significant Difference ◽  
Cell Repopulation

ObjectivesTo examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab.Patients and MethodsBAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse more than 3 months after repopulation (D-R, n=11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n=5). Serum BAFF was measured by ELISA and analysed using Mann–Whitney.ResultsThere was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p<0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p<0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p<0.05).ConclusionBAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.

scholarly journals Study on Serum miR-204 Expression Levels in Patients with Severe Pneumonia and Patients with Primary Bronchial Lung Cancer and Its Diagnostic Value

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wenhong Zheng ◽  
Wei Huang ◽  
Xuchao Yu
Keyword(s):  
Lung Cancer ◽  
Severe Pneumonia ◽  
Diagnostic Value ◽  
Control Group ◽  
Qrt Pcr ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Difference ◽  
The Relationship ◽  
Low Expression

Objective. To analyze the expression and clinical significance of miR-204 in the serum of patients with severe pneumonia (SP) and primary bronchial lung cancer (LC). Methods. 65 SP patients and 43 primary bronchial LC patients who were treated in the hospital from January 2017 to December 2018 were randomly selected as the SP group and LC group. At the same time, healthy patients from the physical examination department of the hospital were selected. 65 cases were the control group. QRT-PCR detected serum miR-204 expression and compared the differences between groups. The pathological data of patients were collected, and the relationship between serum miR-204 and the patient’s pathological data was compared; the area under the ROC curve and Kaplan–Meier curve were used to evaluate the diagnostic value of serum miR-204 for the two conditions and to explore the relationship between serum miR-204 and prognosis. Results. The serum miR-204 of the SP group was (0.43 ± 0.09), the serum miR-204 of the LC group was (0.40 ± 0.10), the serum miR-204 of the control group was (1.00 ± 0.09), and the miR-204 level of was significantly higher than that of the control group, and the difference between the groups was statistically significant ( P  < 0.05). There was no significant difference in serum miR-204 levels between the SP group and the LC group ( P  > 0.05). Serum miR-204 levels in SP patients with cumulative organs ≥3 were higher than those with cumulative organs <3, and the difference was statistically significant ( P  < 0.001). In the LC group, in patients with stage III to IV and low and undifferentiated patients, the level of miR-204 was higher than that of stage I∼II and high and moderately differentiated patients, and the difference was statistically significant ( P  < 0.001). The level of miR-204 in the two groups of patients (0.89 ± 0.10, 0.83 ± 0.13) who died of illness was significantly higher than that of the surviving patients (1.00 ± 0.11, 1.00 ± 0.10), and the difference was statistically significant ( P  < 0.05); the survival rate of patients with high expression of miR-204 was higher than that of patients with low expression. The AUC of serum miR-204 level to SP and LC was 0.766 and 0.818, respectively. Conclusion. The level of miR-204 in the serum of SP patients and patients with primary bronchial LC was significantly lower than that of healthy people, and patients who died were lower than those who survived; the miR-204 in serum has a good diagnostic value for SP and LC and is related to the survival and prognosis of patients.

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