scholarly journals Changes of Peripheral Blood Lymphocyte Subsets and Cytokines in Patients with Multiple Myeloma and Their Clinical Significance

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Li Fei

Objective: Accumulating evidence have indicated that immune response play an essential role in development of multiple myeloma (MM),To evaluate the immune function of patients with MM by detecting the levels of lymphocyte subsets and cytokines, and to analyze the correlation between the immune function and prognosis of patients. Methods: we examined 50 patients with newly diagnosed MM, 20 patients with Relapse / refractory MM and 30 healthy volunteers. the levels of T lymphocyte subsets, activated T cells subtypes, Treg and cytokines in peripheral blood were detected by flow cytometry (FCM).Results: ① compared with healthy control group, CD3 + CD4 + T cells of newly diagnosed MM patients were significantly decreased (P = 0.04), There was no significant difference in CD3+CD8+T and CD4/CD8 of newly diagnosed MM patients with normal controls (P=0.14).The percentage of CD16 + cd56dim NK cells of newly diagnosed MM was significantly lower than that of the normal control group (P = 0.01); There was no significant difference in frequencies of CD3+CD4+T cells, CD4/CD8, CD16+CD56dimNK (P=0.34, P=0.561, P=0.88) between newly treated MM patients and relapsed/refractory MM; HLA-DR-CD8+ activated TS cells of newly diagnosed MM was significantly higher than the normal control group (P = 0.04).② The proportion of CD4 + CD25 + CD127dim T cells(treg) in total CD4 + T cells in of newly diagnosed MM was higher than that in normal control group (P < 0.05). The CD4 + CD25 +CD127dim T cells of MM patients with relapse / refractory MM was higher than that of newly treated patients, but the difference was not statistically significant (P > 0.05). Further analysis showed that CD4 + CD25 + CD127dim T cells in mSMART stratified high-risk group were higher than those in low-risk group (P = 0.03). The number of CD4 + CD25 + CD127dim T cells in patients without PR after 2 courses of PAD was higher than that in patients with≥ PR, but the difference was not statistically significant (P > 0.05). ③ The levels of IL-6, IL-8, TNF - α of newly diagnosed MM were significantly higher than normal control group, and were positively correlated with ISS stage (r=0.61, r=0.67, r=0.59, P均<0.05).④ The levels of IL-6 and IL-8 of newly diagnosed MM with renal injury were significantly higher than those in patients with normal renal function (P < 0.05). Further studies showed that the level of IL-8 was negatively correlated with the proportion of CD16 + CD56dimNK cells (r=-0.65, P<0.05).Conclusion: the abnormal expression of lymphocyte subsets and cytokine levels in MM patients may be related to the tumor load, disease progression and prognosis. Disclosures No relevant conflicts of interest to declare.

2016 ◽  
Vol 40 (3-4) ◽  
pp. 743-756 ◽  
Author(s):  
Xiao-Jie He ◽  
Yan Ding ◽  
Wei Xiang ◽  
Xi-Qiang Dang

Background/Aims: The study aims to elucidate the roles of 1,25(OH)2D3 and vitamin D receptor (VDR) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by regulating the activation of CD4+ T cells and the PKCδ/ERK signaling pathway. Methods: From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH)2D3 and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR). Density gradient centrifugation was performed to separate peripheral blood mononuclear cells (PBMCs). CD4+ T cells were separated using magnetic activated cell sorting (MACS). CD4+T cells in logarithmic growth phase were collected and assigned into 9 groups: the normal control group, the normal negative control (NC) group, the VDR siRNA group, the RA control group, the RA NC group, the VDR over-expressed RA group, the SLE control group, the SLE NC group, and the VDR over-expressed SLE group. The mRNA and protein expressions of VDR, PKCδ, ERK1/2, CD11a, CD70 and CD40L were detected by RT-qPCR and Western blotting. Bisulfite genomic sequencing was conducted to monitor the methylation status of CD11a, CD70 and CD40L. Results: Compared with healthy controls, serum 1,25(OH)2D3 level and VDR mRNA expression in peripheral blood were decreased in SLE patients and RA patients. With the increase of concentrations of 1,25(OH)2D3 treatment, the VDR mRNA expression and DNA methylation levels of CD11a, CD70 and CD40L were declined, while the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L were elevated in SLE, RA and normal CD4+T cells. Compared with the SLE contro, RA control, SLE NC and RA NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L decreased but DNA methylation levels of CD11a, CD70 and CD40L increased in the VDR over-expressed SLE group and VDR over-expressed RA group. However, compared with the normal control and normal NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the VDR siRNA group. Compared with the normal control group, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the SLE control and RA control groups. Conclusion: Our study provide evidence that 1,25(OH)2D3 and VDR could inhibit the activation of CD4+ T cells and suppress the immune response of SLE and RA through inhibiting PKCδ/ERK pathway and promoting DNA methylation of CD11a, CD70 and CD40L.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3763-3763
Author(s):  
Yunfeng Hao ◽  
Renchi Yang ◽  
Zeping Zhou

Abstract Background: Immunological thrombocytopenia (ITP) is an antibody-mediated autoimmune disease characterized by accelerated platelet destruction and suboptimal platelet production. The proliferation-inducing ligand (APRIL or TNFSF13), a member of the TNF superfamily, is structurally and functionally related to the TNF family of B cell activating factors (BAFF, TNFSF13b) and has been shown to regulate lymphocyte survival by interacting with its receptors. And activation. Transmembrane activators and calcium regulate cyclophilin ligand interactors (TACI) and B cell mature antigens (BCMA). APRIL is secreted by various cells as soluble factors, including inactive B cells, T cells, monocytes, neutrophils, macrophages and dendritic cells, as well as epithelial cells, osteoclasts and megakaryocytes. Recent studies have shown that APRIL not only participates in normal immune responses, but also plays an important role in the establishment and/or maintenance of autoimmune and inflammatory diseases. Aims: Based on the relationship between APRIL, which promotes proliferation and regulates immunity, and the development of autoimmunity, we hypothesize that APRIL may play a role in the pathogenesis of ITP. Methods:1. The EDTA anticoagulated whole blood was collected, and peripheral blood mononuclear cells (PBMC) were separated by Ficoll density gradient centrifugation. The APRIL levels on the surface of T cells, B cells, DC cells and platelets were detected by flow cytometry.Detection of plasma APRIL levels in patients with ITP by ELISA.Real time quantitative PCR were used for detecting the level of APRIL and its receptors BCMA and TACI from PBMC of healthy controls and ITP patients.Use soluble APRIL or BLyS protein and APRIL inhibitors to examine the effect of APRIL inhibition on IL-10 secretion by B cells. Flow cytometry and intracellular staining were used to evaluate B10 cells. Resoult: 1. The APRIL on the platelet surface of patients with ITP was significantly lower than that of the normal control group (p<0.01). In the ITP patients of 10 patients with complete remission, the content of APRIL on the platelet surface was significantly increased after treatment (p=0.02), and there was no significant change in the treatment-ineffective group. . The levels of APRIL and its receptors BCMA and TACI on B cells and DC cells in ITP patients were higher than those in normal controls, and the difference was statistically significant. APRIL is not expressed on CD4 + T cells, CD8 + T cells.The expression of APRIL mRNA in PBMNCs was significantly higher in ITP patients than in the normal control group (p <0.01). There was no difference in BCMA and TACI expression in PBMNC of ITP patients compared to normal controls.Plasma APRIL levels were significantly higher in ITP patients than in the normal control group, p = 0.04, and negatively correlated with platelet count, p = 0.029.In 10 patients with ITP, the percentage of CD19 + B cells remained similar between patients, and the results showed that the amount of B10 cells in the medium supplemented with APRIL was greater than that of B10 cells containing BLyS and control medium (p<0.01; p= 0.01), and the use of APRIL inhibitors resulted in a decrease in B10 cells. Conclusion: Our study shows that aberrant expression of APRIL is involved in the autoimmune response of ITP, and the effect of treatment can be assessed by measuring changes in the level of APRIL on the platelet surface. We also speculate that APRIL inhibits, rather than promotes, an immune-mediated inflammatory response in the pathogenesis of ITP. Our current observations support that the immunomodulatory effects of APRIL may be due, at least in part, to stimulation of IL-10 producing B cells. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Nerdy Nerdy ◽  
Linta Meliala ◽  
Bunga Rimta Barus ◽  
Puji Lestari ◽  
Selamat Ginting ◽  
...  

Male infertility has occurred rapidly in the last few decades, primarily in developing countries. An antioxidant, hesperetin is a flavonoid that is found in abundance in orange peels. The aims of this research were to determine the effect of hesperetin on blood sugar levels, spermatozoaquality, and spermatozoa quantity. The research structure included induction of diabetes mellitus and treatment for 8 weeks, followed bydetermination of blood sugar levels, spermatozoa quality, and spermatozoa quantity. Hesperetin has the ability to restore blood sugar levels, spermatozoa quantity, seminiferous tubules diameter, and testicular weight, volume, and germinal epithelial layer thickness with significant difference from the normal control group. Hesperetin did not fully restore spermatozoa motility, viability, and morphology with significant difference from the normal control group, nor from the positive control group. However, overall, hesperetin decreased blood glucose levels, increased spermatozoa quantity, and improved the spermatozoa quality in alloxan-induced diabetes mellitus mice. Dose-dependent activity was observed with the optimum dose at 200 mg/kg body weight.


Author(s):  
Dhaval B. Patel ◽  
S. K. Raval ◽  
G. C. Mandali ◽  
A. C. Patel ◽  
A. M. Pande

The experiment was conducted on 90 adult healthy Wistar rats. Rats were randomly divided in to 15 equal groups, each of 6 rats, and were kept in separate cages. Group I served as normal healthy control without any treatment, while Group II and III served as vehicle (bicarbonate) control and lithiatic control, respectively. In rats of Group III to IX urolithiasis was induced using 0.75 % (v/v) ethylene glycol and 2% (w/v) ammonium chloride in drinking water for 28 days. The rats of Group I, II, and X to XV were given pure wholesome water till 28 days. After 28th day, the rats of urolithiatic treatment Groups IV, V, VI, VII, VIII and IX were given aqueous and alcoholic extracts of Bryophyllum calycium and Solanum xanthocarpum @ 300 mg/kg bwt orally as either single extract or combination as biherbal extracts in 0.5 % sodium bicarbonate using syringe and rat lavage needle, and so also was done for rats of Group X to XV as extract control groups. Blood samples were collected twice: i.e. on day 28 of induction of urolithiasis and then on day 56 of experiment from all rats. No significant difference was observed in any of the haematological parameters and even in serum albumin and globulin levels before and after treatment in different groups. However, increased levels of serum BUN, uric acid and creatinine were observed in the urolithiatic groups as compared to the normal control group on 28th day. While serum total protein levels were decreased in the calculi induced groups as compared to the normal control group. However, co-treatment of aqueous or alcoholic extract of Bryophyllum calycinum and Solanum xanthocarpum significantly restored these changes by 56th day. The effect of biherbal alcoholic extract of the plants was much better in restoring the values and the levels came nearer to normal by 56th day of oral treatment proving nephroprotective effect of these extracts.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Nange Zhao ◽  
Tingting Zhang ◽  
Yujuan Zhao ◽  
Jianping Zhang ◽  
Keqiang Wang

Objective. To investigate the quantity of CD4+T, CD4+T, CD8+T, and γδT cells in peripheral blood of HIV-infected/AIDS patients as well as to explore the possible role of CD4/CD8 ratio and γδT cells in the progression of HIV/AIDS, aimed at providing evidence for the diagnosis and treatment of AIDS. Methods. The quantity levels of CD3+T cells, CD4+T cells, CD8+T cells, and γδT cells in peripheral blood of 46 HIV-infected/AIDS patients and 30 healthy controls were detected by using flow cytometry. Results. The count of CD3+T, CD4+T, CD8+T, and γδT cells ( x ¯ ± s , A/μl) in the peripheral blood was 1183.64 ± 132.58 , 278.39 ± 122.38 , 863.13 ± 82.38 , and 22.53 ± 1.74 in the experimental group as well as 1456.46 ± 124.37 , 788.74 ± 189.67 , 569.61 ± 46.49 , and 10.96 ± 0.28 in the control group, respectively. The p values of the two groups were <0.005 after the t -test, revealing a statistically significant difference. The proportion of CD3+T, CD4+T, CD8+T, and γδT cells in total lymphocytes in the two groups ( x ¯ ± s , %) was 71.83 ± 5.37 , 13.39 ± 2.23 , 62.93 ± 5.81 , and 3.67 ± 0.87 in the experimental group, respectively. In the control group, the values were expressed as 66.72 ± 5.48 , 42.77 ± 3.38 , 31.41 ± 3.62 , and 1.73 ± 0.36 , respectively. After performing the t -test, p values in the two groups were <0.005 except CD3+T, with statistically significant differences. Besides, CD4/CD8 was 0.33 ± 0.11 in the experimental group and 1.48 ± 0.29 in the control group, t = 26.528 , p < 0.001 , exhibiting a significant statistical difference. Conclusion. HIV infection induces the activation and proliferation of CD8+T and γδT cells, contributing to the decrease of CD4+T cells, while CD8+T and γδT cells are involved in the immune response and tissue damage after HIV infection.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3154-3154
Author(s):  
Jinuo Wang ◽  
Jian Li ◽  
Xinxin Cao ◽  
Hao Cai ◽  
Ai-lin Zhao ◽  
...  

Abstract Introduction Almost all multiple myeloma (MM) cases were progressed from a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS). So far, the pathogenesis of myeloma is not yet clear. The immune cells in the tumor microenvironment, such as regulatory T (Treg) cells with a unique immunosuppressive function, play an important role in myelomagenesis. Although there have been reports on Treg cells in MM patients, the results were still in debate. In this study, we performed a comprehensive analysis of peripheral blood (PB) and bone marrow (BM) Treg subsets and aging Treg-like cells in untreated MM patients and individuals with MGUS, which might help further elucidate mechanisms of immune dysfunction during myelomagenesis. Methods Our study included 20 MGUS patients and 26 newly diagnosed MM patients. Flow cytometry was applied to determine the proportion of Treg cell subsets and aging Treg-like cells in PB and BM. Flow sorting technology was used to separate Treg cell subsets and effector T cells in the bone marrow of newly diagnosed MM patients. The inhibitory function was indirectly calculated by detecting proliferation rate of CFSE-labelled effective T cells which were cocultured with different Treg cell subsets. Concentration of IL-10 from the culture supernatants of proliferation assay was measured using ELISA. Results In PB, the proportion of activated Tregs (aTregs, CD4+CD45RA-FoxP3hi) in CD4+ T cells was significantly higher in MGUS and untreated MM patients than healthy controls (P=0.01, P<0.001); there was no difference in the proportion of resting Tregs (rTregs, CD4+CD45RA+FoxP3lo) between MGUS and untreated MM patients compared with healthy adults (P=0.72, P=0.07). There was also no significant difference in the frequencies of non-Tregs (CD4+CD45RA-FoxP3lo) from MGUS and MM patients with normal controls (P=0.22, P=0.67). The proportion of CD4+CD28-FoxP3+ Treg-like cells in CD4+ T cells was gradually increased in MGUS, untreated MM patients than healthy controls (P<0.01, P<0.01); Treg-like cells in newly diagnosed MM patients were significantly higher than those in MGUS patients (P=0.01). In BM, the proportion of aTregs was significantly higher in MGUS, untreated MM patients compared with healthy controls (P<0.01); the proportion of rTregs in MGUS, untreated MM patients was significantly lower than that of controls (P=0.02, P<0.01). However, there was no significant difference in the frequencies of non-Tregs in BM from MGUS and MM patients with normal controls (P=0.14, P=0.88). The proportion of Treg-like cells in CD4+ T cells was significantly higher in MGUS, untreated MM patients compared with healthy controls (P<0.01, P<0.01). Treg-like cells in untreated MM patients were significantly higher than those in MGUS patients (P<0.01). The inhibition rate of aTreg in bone marrow of newly diagnosed MM patients was significantly higher than that of rTreg (P<0.01), while the inhibition rate of non-Treg was significantly lower than that of rTreg cells (P<0.01). The inhibition rates of aTreg (P=0.21), rTreg (P=0.08) and non-Treg (P=0.09) in healthy controls were no difference from those in MM patients. The level of IL-10 secreted by non-Treg in untreated MM patients was notably higher than that of aTreg and rTreg; the ability of cytokine secretion of Treg subsets in MM patients was similar with that of healthy controls. Conclusions There were significant changes in the frequencies of Treg cell subsets and Treg-like cells in peripheral blood and bone marrow of MGUS and MM patients, suggesting that immunomodulatory abnormality has existed in patients at premalignant stage. The immunosuppressive and cytokine secretory functions of Treg subsets in bone marrow of untreated MM patients were intact compared with that in healthy adults. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 36 (7) ◽  
Author(s):  
Yang Li ◽  
Han-liang Jiao ◽  
Yu-kun Bai ◽  
Ping Wang

Objective: To explore the effect of manipulative reduction combined with air enema on intestinal mucosal immune function in children with intussusception. Methods: This is a prospective randomized controlled study in which 60 children with primary intussusception admitted to Hebei Children’s Hospital from October 2018 to October 2019 were selected for this study. They were randomly divided into two groups. The 30 patients in the experimental group underwent manipulative reduction and air enema reduction, and 30 patients in the control group underwent only air enema reduction. Pain scores and pressure during enema were recorded and analyzed. Fasting blood of children in the experimental group were drawn to test the serum T lymphocyte subsets CD3+, CD4+, CD8+ levels, B lymphocyte subsets CD19+ level, and NK cell subsets CD56+ levels before reduction. Among them, fasting blood of 28 children with successful reduction were drawn again in the morning after reduction, and the indicators of each immune cell subgroup before and after reduction were analyzed. Two children with unsuccessful reduction were no longer tested for these indicators. Results: Twenty-Eight children in the experimental group had successful reduction, and two children with unsuccessful reduction were changed to open surgery (28/30). Twenty five Children in the control group had successful reduction, and five were changed to open surgery (25/30). There was no significant difference in the success rate of reduction between two groups (p>0.05). Close observation for 12~24h after reduction found that none of the children had signs of peritonitis. The pain score and reduction pressure of the observation group were lower than those of the control group, and the difference was statistically significant (p<0.05). The levels of serum CD3+, CD4+, and CD8+ after reduction in the experimental group were significantly higher than before reduction, and the difference was statistically significant (p<0.05). CD19+ level was significantly lower than before reduction, and the difference was statistically significant (p<0.05). There was no significant difference in changes of other indicators. Conclusions: Manipulative reduction combined with air enema reduction can relieve pain and air injection pressure during enema, reduce reperfusion injury caused by intestinal ischemia, and protect intestinal mucosal immune function, which is a favored treatment. doi: https://doi.org/10.12669/pjms.36.7.3105 How to cite this:Li Y, Jiao H, Bai Y, Wang P. Effect of manipulative reduction combined with air enema on intestinal mucosal immune function in children with intussusception. Pak J Med Sci. 2020;36(7):---------. doi: https://doi.org/10.12669/pjms.36.7.3105 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Author(s):  
Haiyan Fu ◽  
Hongjuan Li ◽  
Xiaoqing Tang ◽  
Xiang Li ◽  
Jie Shen ◽  
...  

AbstractObjectiveTo analyze the clinical characteristics of patients with novel coronavirus pneumonia in Kunming City, and to study the correlation between nutritional status and immune function.MethodsClinical data of 36 patients with novel coronavirus pneumonia in isolation area of Kunming Third People’s Hospital from January 31 to February 15, 2020 were collected, and the basic situation, clinical characteristics, laboratory examination and CT imaging characteristics were analyzed. Serum albumin (ALB), prealbumin (PAB), hypersensitive c-reactive protein (hs-crp), CD3T cells, CD4T cells, CD8T cells and normal control group were analyzed. A simple linear regression analysis of the relationship between proalbumin and T cell subpopulation counts in the blood of patients.Results(1) The patients with new coronavirus pneumonia in Kunming were mainly of common type. (2) 50% of the patients’ first symptoms were fever and cough; (3) The total number of white blood cells in peripheral blood was normal or decreased in 23 cases (79%), and the lymphocyte count decreased in 5 cases (13.89%), without anemia. Hypersensitive c-reactive protein increased in 19 (52.78%) cases, and procalcitonin increased in 1 case. Albumin decreased in 5 cases (13.89%), proalbumin decreased in 15 cases (41.67%), alanine transaminase increased slightly in 4 cases (11.11%), alanine transaminase increased slightly in 4 cases (11.11%), total bilirubin increased slightly in 11 cases (30.56%), and renal function and blood coagulation were normal. Absolute value of CD3+T cells is with a decrease in 21 cases (58.3%), CD4+T in 28 cases (77.8%), CD8+T in 17 cases (47.2%), and CD4+/ CD8+ inverse in 6 cases (16.7%). (4) The prealbumin, CD3 T cells, CD4 T cells and CD8 T cells in the new coronavirus pneumonia group were significantly lower than those in the normal control group, and the hypersensitive c-reactive protein was higher than that in the normal control group. (5) The levels of PAB in the serum of the patients were linearly correlated with hs-crp, CD3 T cells, CD4 T cells and CD8 T cells, and the correlation coefficients were −0.474, 0.558, 0.467 and 0.613, respectively, showing statistical differences.ConclusionThe clinical characteristics of the novel coronavirus pneumonia in Kunming are different from those in Wuhan. The changes of serum proalbumin and T cell subsets are relatively obvious. Changes in serum proalbumin may contribute to the early warning of novel coronavirus pneumonia. The nutritional status of patients with common and mild pneumonia should be considered.


2020 ◽  
Vol 24 (8) ◽  
pp. 1335-1340
Author(s):  
M. Dikko ◽  
Y. Sarkingobir

The objective of this study was to investigate histopathology of livers and carry out body weight determination in normal rats administered with  tamsulosin. Standard methods and procedures were used in this study. The results were revealed. Pertaining weight, at the 3rd , 6th and 8th weeks of the study, no significant difference (P>0.05) in weight was found in the group of rats treated with carvedilol (positive control), tamsulosin low dose (12μg/kg) and high dose tamsulosin (40μg/kg) compared to normal control group, respectively. Other inter-groups comparisons were not significantly different, respectively. Pertaining liver morphology, liver sections of groups revealed no significant histological lesions compared to the normal control group at the 6th and 8th weeks of the study, respectively. This study revealed that the tamsulosin cause no histopathological lesion, thus the drug might be safe to the liver and its biochemical processes. Keywords: Tamsulosin, Liver, histopathology, weight, Wistar rats


1984 ◽  
Vol 15 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Carol Swift

The Carrow Elicited Language Inventory was used to compare the imitation skills of kindergarten children identified as high risk for learning disability with those of a normal control group. A significant difference was found between the two groups in the total number of errors. Differences were also found in the ability to imitate adjectives, conjunctions, pronouns, and verbs. An incidental finding, failure on the part of many high-risk subjects to imitate interrogative stimuli, is discussed in terms of a processing deficit.


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