Imbalance Of Cellular Immunity Research Articles

Homeostatic Modulation of CD4+ T Cell Subsets Using the Chinese Medicine Jianpi Qushi Heluo Formula During the Alleviation of Primary Membranous Nephropathy

ABSTRACT Background: Compelling evidence suggests that the immune system plays a key role in the development and progression of primary membranous nephropathy (pMN). The Jianpi Qushi Heluo Formula (JQHF) is an empirical and effective traditional Chinese medicine prescription used for the clinical treatment of pMN in China. However, it remains unclear whether JQHF treatment affects the peripheral immune system of patients with pMN. Methods: Twenty-five patients with pMN and 10 healthy controls (HC) were enrolled. Patients with pMN were treated with JQHF for 6 months. Circulating CD4+ T cell subsets and associated chemokines were analyzed using flow cytometry among both HC and pMN before and after 6 months of JQHF treatment. Results: Patients with pMN treated with JQHF achieved 60% clinical remission and a significant reduction in 24-hour urinary protein excretion (24hUTP). Compared to HC, Th1 cells increased, Treg cells decreased, and Th1/Th2, Th1/Treg, and Th17/Treg cells increased in the pMN (P = 0.011, P = 0.035, P = 0.001, P = 0.026, P = 0.038, respectively). JQHF treatment significantly improved cellular immune imbalance in patients with pMN. Patients with pMN showed increased levels of peripheral blood C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, and C-C motif ligand 20 (CCL20), but no significant difference was observed compared with HC. JQHF treatment significantly reduced CXCL10 levels (P = 0.0071). Moreover, 24hUTP was strongly and positively correlated with Th1 cell and CXCL10 levels (P = 0.0438 and P = 0.0211, respectively). Total serum protein levels were strongly and positively correlated with Tregs (P = 0.0816). Th1 cells also strongly and positively correlated with CXCL10 levels (P = 0.0012). Conclusion: Our findings suggest an imbalance in the immune differentiation of peripheral blood CD4+ T cells in patients with pMN. JQHF treatment had a pronounced effect on pMN, which may be mediated by the improvement of homeostatic modulation of CD4+ T cell subsets.

PD05-06 INFECTION PHENOTYPE IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME: DOES BACTERIAL-INDUCED MUCOSAL CELLULAR IMMUNE IMBALANCE HYPERSENSITIVITY EXPLAIN RESPONSE TO MV140 RECURRENT UTI VACCINE?

You have accessJournal of UrologyCME1 Apr 2023PD05-06 INFECTION PHENOTYPE IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME: DOES BACTERIAL-INDUCED MUCOSAL CELLULAR IMMUNE IMBALANCE HYPERSENSITIVITY EXPLAIN RESPONSE TO MV140 RECURRENT UTI VACCINE? J. Curtis Nickel, Kerri-Lynn Kelly, Ashley Griffin, and R. Christopher Doiron J. Curtis NickelJ. Curtis Nickel More articles by this author , Kerri-Lynn KellyKerri-Lynn Kelly More articles by this author , Ashley GriffinAshley Griffin More articles by this author , and R. Christopher DoironR. Christopher Doiron More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003229.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent UTI (rUTI) associated with symptom flares. rUTI subjects with associated IC/BPS were enrolled in the First North American Early Clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. Recent research shows that women with rUTI develop an imbalance in the T Helper 1 and 2 (Th2 over expression) in the bladder mucosa. Our study will suggest that this infection subcategory of IC/BPS patients develop a T Helper 2 (Th2)-type hypersensitivity (or allergy) to bacteria present in their urinary microbiome that responds to mucosal immune modulation. METHODS: Female participants with ≥3 documented UTI/year underwent a 3 month vaccination treatment period with a 9 month efficacy period after completion of vaccine treatment (total 12 months). There was no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient reported subjective global assessment (responder defined as moderately or markedly improved on 7-point SGA scale) and safety. RESULTS: Sixteen subjects with IC/BPS related symptoms and rUTI (mean age 46.6; range 23-74 years; mean number of UTI in previous year 6.1+/-4.2) were eligible to be included in the Health Canada approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3 month vaccination period. One subject lost to followup after 6 month visit. Six subjects were UTI-free while all 16 subjects had a reduction in UTI compared to the year pre-vaccination. The total post-vaccination reduction in UTI compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month respectively) At 12 months, 13 subjects (81.3%) were SGA responders (moderately or markedly improved) and the responders reported a reduction in IC/BPS symptoms with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self limited adverse events during vaccination period but none were related to MV140 vaccine. CONCLUSIONS: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only report UTI-free or reduced UTI incidence status but also after approximately 9 months post vaccination, many have resolution of their-long term treatment refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on a Th2 cell type hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system. Source of Funding: Inmunotek provided MV140 vaccine © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e150 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information J. Curtis Nickel More articles by this author Kerri-Lynn Kelly More articles by this author Ashley Griffin More articles by this author R. Christopher Doiron More articles by this author Expand All Advertisement PDF downloadLoading ...

Prediction of the course and consequences of infectious mononucleosis caused by the Epstein-Barr virus

Abstract. The study of the role of Epstein-Barr viral infection in the occurrence of various pathological conditions in humans is of great importance. This is due to the significant epidemiological role, since upon reaching the age of majority, more than 90% of people are infected of Epstein-Barr virus. The steady increase in the number of diseases caused by Epstein-Barr virus both among adults and children, which is associated with its specific tropism for immunocompetent cells, lifelong persistence and latent course necessitates a comprehensive study and development of effective treatment methods. Purpose of the work: to assess clinical and immunological parameters in order to identify a protracted course and predict unfavorable outcomes in patients with infectious mononucleosis caused by the Epstein-Barr virus. Materials and methods: To achieve this purpose, 60 patients with infectious mononucleosis were examined, among them 38 women (63.3%), 22 men (36.7%). The average age of the patients was 24.3±4.3 years. The material for the study was the patient's serum obtained in the dynamics of the disease. The complex of examination of patients with Infectious mononucleosis included clinical and biochemical methods, enzyme-linked immunosorbent assay, polymerase chain reaction method, immunogram. The research results were processed by the method of variation and correlation statistics using the Statistica 10.0 for Windows program. Results. The analysis of the obtained results made it possible to establish that in patients with infectious mononucleosis, changes were revealed in the system of cellular and humoral immunity and its multidirectionality. The progressive nature of changes in immune parameters indicates the formation of a secondary cellular immune imbalance, activation of the humoral link, a change in the balance of immunoregulatory mediators towards Th2 cells. In the acute period, statistically significant violations of the cellular link of immunity were established, which were characterized by an increase in the number of cells with killer activity: mature T-lymphocytes (CD3+), cytotoxic T-suppressor cells (CD8+), cells expressing the activation marker CD25+ (IL-2 receptor ) and increased Th1/Th2. Conclusions. Thus, changes in the cellular and humoral links of immunity in a favorable course of myocardial infarction are characterized by activation of the cellular and humoral links of immunity, which is manifested by an increase in the content of lymphocytes in the peripheral blood with the [CD3+; CD4+; CD8+; CD16+; CD20+], Th1 cells, IgA and IgM; (p<0.05) with a tendency to normalization during the period of convalescence. With the formation of chronic forms of Epstein-Barr viral infection, a progressive nature of changes in immune parameters is noted, which indicates the formation of a secondary lymphocytic cellular imbalance, activation of the humoral link, a change in the balance of immunoregulatory mediators towards Th2 (a decrease in the content of [CD3+; CD4+; CD8+; CD16+]; an increase in the content of CD20+; IgG levels; Th2 (IL-4+) Th1/Th2 (p<0.05) due to an increase in the relative content of Th2 cells.

Clinical and immunological efficiency of different therapy schemes in patients with infectious mononucleosis caused by Epstein-Barr virus

Abstract. The study of the role of Epstein-Barr virus infection in the development of various human pathological conditions is of great importance. This is due to the significant epidemiological role and social significance, because according to epidemiological data, more than 90 % of people are infected with VEB when they reach adulthood. The steady increase in the number of diseases caused by VEB in both adults and children is associated with its specific susceptibility to immunocompetent cells, lifelong persistence and latent course, which necessitates a comprehensive study and development of effective treatments. The aim of this study was to evaluate the effectiveness of ribonucleic acid in the correction of immune disorders in patients with infectious mononucleosis caused by Epstein-Barr virus. Materials and methods: To achieve this goal, 110 patients with IM were examined, including 58 women (52.7 %), men – 52 (47.3 %). The mean age of patients was 23.3 ± 4.2 years. The material for the study was the serum of patients obtained in the dynamics of the disease. The complex of examination of patients with IM included clinical and biochemical methods, enzyme-linked immunosorbent assay, polymerase chain reaction method, immunogram. The results of the research were processed by the method of variation and correlation statistics using the program «Statistica 10.0 for Windows». The analysis of the obtained results allowed to establish that in patients with IM changes in the system of cellular and humoral parts of the immune system and the diversity of the immune response were detected. The progressive nature of changes in immune parameters indicates the formation of secondary cellular immune imbalance, activation of the humoral link, a change in the balance of immunoregulatory mediators towards Th2 cells. In the acute period, probable disorders of the cellular immune system, characterized by an increase in the number of cells with killer activity: mature T-lymphocytes (CD3+), cytotoxic T-suppressor cells (CD8+), cells expressing the activation marker CD25+ (receptor IL2) and increase Th1/Th2. Under the influence of complex immunomodulatory and antiviral action with the appointment of ribonucleic acid, there is a more positive dynamics of immunological parameters compared with patients who received only basic therapy, which is manifested by an increase in the proliferative response. Conclusions. For the correction of immune disorders in patients with IM, associated with VEB the use of complex therapy with the drug nuclex (ribonucleic acid) (250 mg) 2 capsules 3 times a day for 14 days and valaciclovir (500 mg) at a dose of 1000 mg (2 table) 3 times a day for 14 days.

Clinical and immunological efficiency of different therapy regimens in patients with infectious mononucleosis caused by Epstein-Barr virus

The aim of the study was to evaluate the effectiveness of ribonucleic acid in the correction of immune disorders in patients with infectious mononucleosis (IM) caused by EBV.
 Materials and methods. We examined 110 patients with a mean age of 23.3±4.2 years with IM, among whom women accounted for 52.7 % (n=58). The material for the study was the serum of patients obtained during the disease course. The set of tests of patients with IM included clinical and biochemical methods, enzyme-linked immunosorbent assay, polymerase chain reaction method, immunogram. Statistical processing of the obtained data was performed with “Statsoft Statistica v. 10.0 for Windows” using the methods of variation and correlation statistics.
 Results. The obtained results analysis revealed changes in the system of cellular and humoral parts of the immune system and the diversity of the immune response in patients with IM. The progressive nature of changes in immune parameters indicated the formation of secondary cellular immune imbalance, activation of the humoral link, a change in the balance of immunoregulatory mediators towards Th2 cells. Significant changes in the cellular immune system were observed in the acute period and were characterized by the increase in the number of cells with killer activity, namely mature T-lymphocytes (CD3+), cytotoxic T-suppressor cells (CD8+), cells expressing the activation marker CD25+ (IL-2 receptor), and by the Th1/Th2 ratio increase. The appointment of combination therapy including ribonucleic acid was accompanied by immunomodulatory and antiviral effects, that was reflected in a more pronounced positive dynamics of immunological parameters, namely in strengthening the proliferative response, compared with the group of patients receiving only basic therapy.
 Conclusion. The expediency of the combination therapy application: the drug Nuclex (ribonucleic acid) (250 mg) 2 capsules 3 times a day for 14 days and valacyclovir (500 mg) at a dose of 1000 mg (2 tablets) 3 times a day for 14 days, is justified for the correction of immune disorders in patients with IM caused by EBV.

Differential Expression of IL-17 Correlates with Clinical and Pathological Features of ITP

Introduction:Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder, which is characterized by megakaryocyte (MgK) inhibition/destruction in the bone marrow (BM) and/or platelet in the spleen and liver. Abnormal MgKs, which is recognized by autoantibodies, are phagocytosed by macrophages. Recently, it has been demonstrated that interleukin-(IL-)17-mediated cells contribute to the imbalance of cellular immunity in the pathogenesis of ITP. Studies of pathological findings in BM of patients with ITP using immunohistochemistry (IHC) are limited. Therefore, we examined samples of BM clots to test the hypothesis that IL-17-mediated immunological changes are involved in the BM of patients with ITP.Methods:We enrolled 35 patients with a median age of 61 years (range, 19-91 years), who were retrospectively selected at random and were referred to our hospital between 2005 and 2016. All patients were diagnosed with chronic ITP. Twenty-five patients underwent first- or second-line therapies such as glucocorticosteroids, cyclosporine A, azathioprine, danazol and intravenous immunoglobulin and/or splenectomy as conventional therapies. Twenty-three patients who could not undergo those therapies were administered with eltrombopag. BM clots were obtained before treatment and stained with hematoxylin and eosin for morphological examination. Formalin-fixed and paraffin-embedded specimens were used for IHC using antibodies for the following markers: CD3, CD4, CD8, CD20 (L26), CD25, CD68, CD163, and IL-17. Pathological findings and clinical information including laboratory data were compared between the patients with ITP and control subjects, which were obtained from 11 untreated malignant lymphoma patients without the infiltration of lymphoma cells in BM. We also compared those between 2 groups: an IL-17-high-expression group and IL-17-low-expression group.Results:A univariate analysis revealed increased cells expressing the following markers in patients with ITP than in the control subjects: CD20 (5.80 ± 3.46% vs. 3.06 ± 1.90%; p= 0.02), CD68 (11.3 ± 11.1% vs. 3.14 ± 3.23%; p= 0.02), CD163 (5.10 ± 2.74% vs. 2.13 ± 1.10%; p= 0.001), and IL-17 (3.13 ± 1.48% vs. 1.49 ± 1.00%; p= 0.002) and decreased cells expressing following markers: CD4 (0.33 ± 0.71% vs. 1.96 ± 1.13%; p < 0.0001) and CD25 (0.09 ± 0.18% vs. 0.23 ± 0.10%; p= 0.01). The difference of cells expressing CD3 (p= 0.96) and CD8 (p= 0.41) were not statistically significant. There were significant correlations between CD68 and CD163 expressions (r= 0.61). The expressions of both CD68 and CD163 showed correlations with IL-17 expressions (r= 0.61, 0.51). We found significant increased expressions of CD3 (3.98 ± 2.96% vs. 6.37 ± 3.33%; p= 0.03), CD25 (0.05 ± 0.08% vs. 0.17 ± 0.22%; p= 0.03), CD68 (7.84 ± 5.09% vs. 17.3 ± 15.6%; p= 0.01), and CD163 (4.23 ± 2.37% vs. 6.57 ± 2.77%; p= 0.01) in the IL-17-high-expression group (N = 13) compared with IL-17-low-expression group (N = 22). The expressions of CD4 (p= 0.98), CD8 (p= 0.54), and CD20 (p= 0.85) were not statistically significant. Responses to eltrombopag were significantly better in the IL-17-low-expression group than in the IL-17-high-expression group (p= 0.03).Conclusions:By IHC analysis, we report for the first time increased CD68- and/or CD163-expressing cells in the BM of patients with ITP. Those are possibly associated with the pathogenesis of ITP. Our results indicate that CD68- and/or CD163-expressing macrophages and monocytes, but not lymphocytes are involved in deregulated expression of IL-17 in ITP. We demonstrate that the response of eltrombopag is significantly better in the IL-17-low-expression group. These results indicate that patients with ITP, achieving remission early, might belong to the category of the low-IL-17, CD68, and CD163 expressions. We suggest that IHC staining in patients with ITP may be a potential indicator to understand the mechanism of ITP and to predict the prognosis for treatment. DisclosuresNo relevant conflicts of interest to declare.

Assessment of cellular immunity in oil production operators with an imbalance of lipid metabolism

Introduction. Studies indicate the high pathogenetic significance of the immune component in the development of atherosclerosis. The aim of the study is a comparative assessment of immunological parameters in workers of petrochemical production with varying degrees of imbalance in lipid metabolism and the development of the atherosclerotic process. Materials and methods. Men working at an oil production enterprise in the Perm Region were examined. The observation group consisted of oil production operators with a diagnosis of atherosclerosis, the comparison group - with dyslipidemia syndrome. To determine the parameters of lipid metabolism, the results of a biochemical blood test were used. CD-immunogram parameters were identified by flow cytometry. Specific antibodies to benzene were determined by the allergosorbent method. Results. The results of a comparative study of fat metabolism confirmed violations of the physiological ratio of lipids in the blood of oil production workers, which were expressed in a significant imbalance in the levels of lipidogram. There was an increased level of specific IgG antibodies to benzene in the observation group in relation to the comparison group. An imbalance of cellular immunity was found, which was characterized by signs of indicators activation of cellular differentiation clusters. Conclusions. Studies of immune system compartments demonstrate excessive activation of cellular and humoral immunity in oil production workers under the influence of a combination of harmful production factors. The simultaneously formed imbalance of lipid metabolism is associated with various degrees of clinical manifestation of atherosclerotic disorders, with the influence of harmful production factors, aggressiveness of cellular and humoral immunity, and smoking.

Status of cellular immunity in rats under conditions of acute widespread petitonitis in the setting of diabetes mellitus

Acute generalized peritonitis (AGP) occurs in patients with concomitant pathology, in particular at diabetes mellitus. The severity of peritonitis depends on the adequacy of the immune response. Purpose of research was to study the features of cellular arm of immune response in the organism of experimental animals with simulated AGP in the setting of diabetes mellitus (DM). 56 white rats were used in the experiment, which was divided into three groups: main group – 24 animals with simulated AWP in the setting of DM; comparison group – 24 animals with simulated peritonitis. Animals of the main group AGP were modelled by injecting 10 % of filtered fecal suspension into the abdominal cavity of tested rats at a dose of 0,5 ml per 100 g of body weight. Removal of material for histological examination was performed on 1, 3 and 7 days. Cellular immunity was determined by a method based on the interaction of fluorescently labeed monoclonal antibodies with lymphocyte surface antigens. In both animals, all indicators of cellular immunity gradually decreased from day 1 to day 7 of the experiment, but these changes were more significant in animals with DM. With AGP, the cellular immune response imbalance is more significant in animals with DM than in animals with isolated AGP, which is characterized by a marked statistically significant decrease in the level of CD3+ cells, CD4+ cells, CD16+ cells, and a moderate increase in CD8+ cells. The imbalance of cellular immunity deepens depending on the duration of the lesion. The level of CD3+ cells at 1, 3, and 7 day in animals with AGP in the setting of DM was 53,77%, 60,48%, and 62,1 %, respectively, lower than the level in the group with animals with AGP. The prolonged imbalance of cellular immunity indices in experimental animals with simulated AGP in the setting of DM indicates not only the occurrence of secondary immunodeficiency, but also significant depletion of the body’s immune forces compared to animals with AGP.

Immune profile of oil production enterprise employees

Introduction. The assessment of the immune profile of employees of the oil-producing enterprise, the formation of the immunological status of which is determined by the conditions of harmful production factors affecting their health.The aim of the study was to assess the state of cellular immunity in oil-producing enterprise employees (on the example of the Perm region).Materials and methods. 60 men working at the oil-producing enterprise of the Perm region were examined. In the observation group (n=30) were included surveyed male workers-operators of oil production, in the comparison group — surveyed male workers — representatives of the administrative apparatus. The state of cellular immunity was assessed by indicators of cellular regulation and apoptosis. Cell differentiation marker T-reg-CD4+CD127 -, expression level of Bcl–2, Bax, p53 proteins, TNFR receptors and AnnexinV-FITC+7AAD negative cells were determined by flow cytometry.Results. The comparative analysis with physiological norm indicators allowed to reveal reliable hyperproduction of membrane and intracellular factors of cellular immunity in oil production operators. Expression of regulatory marker CD127-, proteins Bax, Bcl–2 and p53, TNFR receptor content and AnnexinV-FITC+7AAD negative cells responsible for natural cell death (p&lt;0.05) was established. The indicators of the observation group differed significantly from those of the comparison group. There was a significant inhibition of expression of CD-marker CD127-and apoptic protein Bcl–2 by more than 10%, an increase in TNFR, AnnexinV-FITC+7AAD negative cells, protein Bax and p53 by 1.3, 1.6 and 1.2 times, respectively.Conclusions. The results of immunological screening allowed to establish an imbalance of cellular immunity in oil-producing enterprise workers — a deficiency of regulatory cells and a protein-controller of cell death with simultaneous excessive activation of cell reception, which later forms the phenomenon of cellular immunodeficiency. The high sensitivity of the membrane and cytoplasmic components of the immune profile allows them to be used as indicators of the health status of oil production operators, timely identify the development of regulatory imbalance of the immune system, early violations of cell-associated pathological processes (cellular immunodeficiency, autoimmune and proliferative processes), as well as timely and effective implementation of measures to prevent the development of production-related diseases working at oil production facilities.

Research of dynamics of immune response indicators in patients with infectious mononucleosis caused by Epstein-Barr virus

Objective. The article is devoted to the study of the content of the main immune parameters in patients with infectious mononucleosis (IM) in the dynamics of the disease. Materials and methods. A clinical examination of IM patients (n = 60) and patients of the control group (n = 20) included the study of complaints, epidemiological history, history of disease and life, objective examination, standard instrumental and laboratory studies in dynamics, detection of EBV DNA in saliva and blood serum, and a comprehensive analysis of immune parameters. The main subpopulations of peripheral blood lymphocytes (CD3 +; CD4 +; CD8 +; CD16 +; CD8 + CD28 +; CD8 + CD28-; CD20 +; CD25 +) were determined by flow laser cytometry on a FACS-Calibur apparatus (USA) using monoclonal antibodies. For identification of INF-γ (Th1-cells), IL-4 (Th2-cells) in the cytoplasm of T-lymphocytes, monoclonal antibodies INF-γ-PC-5, IL-4-PE (eBioscience, Beckman Caulter, R &amp; D System) were used. Results. A comprehensive study of the state of the subpopulations of reacting immune cells revealed significant violations of cellular parts of the immune response compared to the control group. It was established that the immune response in patients with IM during the height of the disease is characterized by an imbalance in the cell link (as evidenced by an increase in the content of CD3+, CD4+, and a simultaneous increase in the content of CD16+, CD25+). In the period of convalescence, violations have been identified that will persist without reaching the levels of the control group in a larger number of IM patients. Conclusion. The results obtained indicate significant changes in the structural characteristics of the cellular immunity system and the multidirectional immune response in IM. The progressive character of changes in immune parameters in IM indicates the formation of a secondary cellular immune imbalance, a change in the balance of immunoregulatory mediators towards the Th2 link during the formation of protracted and chronic forms of EBV-infection.

Diagnosis value and correlation of macrophage stimulating protein with immune regulatory factors in acute-on-chronic liver failure patients

Objective To observe the expression level of macrophage stimulating protein (MSP) in acute-on-chronic liver failure (ACLF) patients, and to explore the clinical significance and correlation with different immune regulatory factors. Methods The double antigen sandwich enzyme-linked immunosorbent assay method was used to detect MSP in the peripheral blood of 45 patients who were diagnosed with ACLF and 32 cases of chronic hepatitis B (CHB). The MSP levels were compared among ACLF patients with different outcomes, and the MSP level of healthy person was used as control. Meanwhile, liver function and hepatitis B virus (HBV) load were detected, and the expressions of peripheral blood CD4+ interferon (IFN)γ+ (helper T cell 1 Th1), CD4+ interleukin (IL)-4+ (helper T cell 2, Th2), CD4+ IL-17+ (helper T cell 17, Th17) and CD4+ CD25+ Foxp3+ (regular T cell, Treg) were measured by flow cytometry. The comparison of means between two samples was done by t test, and one-way ANOVA and linear correlation analysis were also used. Results The serum MSP levels in ACLF patients , CHB group and healthy control were (1.65±0.46) ng/mL, (1.43±0.32) ng/mL and (1.23±0.21) ng/mL, respectively. The serum MSP level in ACLF patients was significantly higher than both CHB patients (t=2.163, P=0.035) and healthy control (t=4.032, P=0.01). The MSP level in ACLF survival group was statistically higher compared with ACLF death group ( ng/mL vs ng/mL, t=1.973, P=0.042). Th2, Th17 cells in ACLF group, CHB group and healthy control group were (1.51±0.27)% and (1.94±1.02)%, (0.42±0.08)% and (0.55±0.36)%, (0.23±0.19) % and (0.26±0.19)%, respectively, which were all significantly different (F=7.759 and 37.229, respectively; both P 0.05). Conclusion MSP is involved in the progress of ACLF, and it may be associated with clinical outcomes and cellular immune imbalance of ACLF patients. Key words: Acute-on-chronic liver failure; Macrophage stimulating protein; Immunity, cellular

Alterations and clinical significance of peripheral blood T lymphocyte subsets in patients with septic acute kidney injury

Objective To investigate the alterations of peripheral blood T lymphocyte subsets in patients with sepsis and septic acute kidney injury, and explore the clinical significance. Methods Fifty-five patients with sepsis and forty-three patients with septic acute kidney injury were enrolled in this study. At the same period, thirty healthy subjects were enrolled as the control group. T lymphocyte subsets including CD3+ T, CD4+ T, CD8+ T cells, and CD4+ T/CD8+ T in peripheral blood were detected by flow cytometry, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) were graded within twenty-four hours after admission. Then, correlation of the APACHE Ⅱ scores and T lymphocyte subsets was analyzed. Results In the septic acute kidney injury group, peripheral blood CD3+ T, CD4+ T cell percentages, and CD4+ T/CD8+ T ratio were significantly lower than those in the control group and the sepsis group (all P<0.05). In the septic acute kidney injury group with stage 3, CD3+ T, CD4+ T cell percentages, and CD4+ T/CD8+ T ratio in the patients were significantly lower than those in stage 1 and stage 2 (all P<0.05). In the septic acute kidney injury group, CD3+ T, CD4+ T cell percentages, and CD4+ T/CD8+ T ratio were significantly lower in dead group than those in survival group (all P<0.05). APACHE Ⅱ scores in patients with sepsis were significantly negatively correlated with peripheral blood CD4+ T cell percentages and CD4+ T/CD8+ T ratio (r=-0.645, -0.492, allP<0.05). Conclusions There are varying degrees of cellular immune imbalance in patients with sepsis and septic acute kidney injury, characterized by decline of circulating CD3+ T, CD4+ T cell percentages, and CD4+ T/CD8+ T ratio. CD4+ T cell percentages and CD4+ T/CD8+ T ratio are closely related to the severity and prognosis of septic acute kidney injury. Key words: Sepsis/CO/IM; Kidney diseases/CO/IM; T-lymphocyte subsets

Advances in pathogenesis of children with chronic refractory immune thrombocytopenia

Chronic refractory autoimmune thrombocytopenia (C/RITP) comprises complex and heterogeneous pathogenesis.Beyond the classic immune disorders such as platelet autoantibodies and cellular immune imbalance, other important considerations that can cause acquired C/RITP include infection, drug, vaccines, autoimmune diseases, tumor, or platelet function disorder.In addition, advances in the molecular mechanism and genetic correlations of C/RITP for children are also discussed. Key words: Chronic refractory autoimmune thrombocytopenia; Pathogenesis; Acquired; Genetic

The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection.

Chronic hepatitis B (CHB) affects 400 million people and is the most common cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) worldwide. Cellular immune regulation plays an important role in determining the infection outcome. Co-signal molecules and Th17/Treg were studied to explore their association with the progression of HBV infection. Ninety-four HBV-infected patients were categorized into three groups: 31 patients with LC caused by CHB, 30 with HCC caused by CHB and 33 with HCC caused by CHB. Co-signal molecules, Th17/Treg, and Stat3 and Stat5 were analyzed by flow cytometry. CHB patients who progressed to LC or HCC showed a significantly higher level of co-inhibitory molecules such as BTLA and PD-1, while there was no significant difference in co-stimulatory molecules among LC, HCC and CHB. Stat3 and Stat5 were significantly increased in LC and HCC compared to CHB patients. Co-inhibitory molecules play more important roles than co-stimulatory molecules. Increased PD-1 and BTLA/HVEM inhibited immune cells and the immune process. At the same time activated Stat3 and Stat5 stimulate the key factors in differentiation of Th17 and Treg, thus leading to imbalanced expansion of Th17 and Treg; immune tolerance was induced and HBV persistent. This resulted in hepatic inflammation that progressed to cirrhosis and carcinoma.