The study of relationship between serum levels of soluble fms-like tyrosine kinase-1 and soluble fibrinogen-like protein 2 with delayed graft function after kidney transplantation

Delayed graft function (DGF) is a transplant complication which means a need to dialysis throughout the first week after transplantation. This study aimed to ascertain the relationship between the two immunomodulatory factors of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble fibrinogen-like protein 2 (sFGL-2) with DGF after transplantation. This case-control study was done in 2 groups of 58 kidney transplant patients with and without DGF. The control group included the patients who didn't show DGF symptoms. Then, serum levels of sFlt-1and sFGL-2 in all blood samples were measured by ELISA. Serum sFlt-1 and sFGL-2 levels were significantly higher in the DGF group compared to those in the control group (p�0.001). sFlt-1 and sFGL-2 serum levels significantly affect DGF (p<0.001) in such a way that they may be diagnostic factors of DGF. This study showed a significant relationship between sFlt-1 as well as sFGL-2 and DGF. Therefore, plasma levels of sFlt-1 and sFGL-2 may be used as diagnostic tools to determine the risk of DGF. © August 2019, Iran J Allergy Asthma Immunol

Effects of submaximal aerobic exercise on regulatory T cell markers of male patients suffering from ischemic heart disease

There are confirmed beneficiary effects of exercise on atherosclerotic inflammation of ischemia-Associated heart diseases. The purpose of this study was to evaluate the effect of aerobic exercise on T-regulatory cell markers of IL-35 as well as FoxP3 and T-helper2 marker of IL-33 in patients with ischemic heart disease (IHD). This research was performed on 44 asymptomatic male patients with ischemic heart disease. The participants were randomly assigned into two groups of submaximal aerobic exercise and control group. Blood samples were collected before and after the termination of the exercise protocol. Serum levels of IL-35 and IL-33 as well as the amount of FoxP3 gene expression in peripheral blood mononuclear cells were measured by Elisa and Real time PCR, respectively. Serum levels of IL-35 (p=0.001) as well as the amount of FoxP3 gene expression increased significantly (p=0.012) in exercise group even after controlling the likely confounding effects of age, length of ischemia, duration of the disease, and the amount of such factors before exercise (p≤0.042). It seems that exercise may yield a better control of atherosclerotic inflammation in patients with ischemic heart disease through the induction of regulatory T cells

The investigation of relevancy between PIAS1 and PIAS2 gene expression and disease severity of multiple sclerosis

Introduction: PIAS1 and PIAS2 (protein inhibitor of activated STAT 1,2) play key roles in the pathogenesis of autoimmune and inflammatory diseases. This study aims to evaluate the gene expression of these factors in multiple sclerosis (MS) patients compared to healthy individuals and correlate them with the severity of MS. Materials and methods: Sixty participants, including 30 patients with MS and 30 healthy controls were studied. The expression of PIAS1 and PIAS2 genes in peripheral blood samples of all participants was measured by real-time PCR. The severity of MS was evaluated using the Expanded Disability Status Scale (EDSS). Finally, we evaluated the correlation between the expression of PIAS1 and PIAS2 genes with disease severity. Results: The expression of PIAS1 gene was increased in patients with MS compared to healthy subjects (P value<.001). Also, there was a significant correlation between the expression of PIAS1 and PIAS2 genes with disease severity according to EDSS. Conclusion: Our study suggests the expression of PIAS1 and PIAS2 genes as a prognostic and diagnostic marker in MS disease. © 2019, © 2019 Taylor & Francis

Association of Regulatory T Cells with Diabetes Type-1 and Its Renal and Vascular Complications Based on the Expression of Forkhead Box Protein P3 (FoxP3), Helios and Neurophilin-1

In recent years, it has been recognized that regulatory T cells (Tregs) play a critical role in maintaining immune tolerance. Moreover, the expression of two markers named Helios and neurophilin-1 (NRP-1) has been highlighted in such cells. Helios, an intracellular transcription marker, largely differentiates twomost operative sub group of Tregs, namely naturally occurring (nTreg) and induced (iTreg) Tregs, and NRP-1 is reckoned as a membranous activity marker of Tregs. We aimed to count peripheral mononuclear cells expressing such markers in a group of type 1 diabetes patients to elucidate the possible role of Tregs in the pathogenesis of such disease and its complications. Blood samples from 61 adult patients with type 1 diabetes and 61 sex and age-matched healthy controls were tested to count two types of Tregs, namely naturally occurring and inducible types, according to the expression of cell surface markers of CD4/CD25/CD47�FITC/PE/APC and intracellular markers of FoxP3/Helios�PE-CY5/eFlour450 by flow cytometry, respectively.We also investigated the relation between expression of such markers with HbA1c, urine albumin/creatinine ratio (UACR), and common carotid intima thickness (CIMT). The circulatory frequency of both Helios+ and Helios- T-cells were significantly decreased in patients compared to those in healthy controls (p<0.001). There was also a significant decrease in circulatory frequency of Helios+ NRP-1+ and Helios- NRP-1+ cells in the patients compared to controls (p=0.029). According to expression of Helios and NRP-1 markers, the number and function of both Tregs were decreased in diabetic patients. Moreover, the neurophilin expression was inversely associated with complications of type 1 diabetes. Copyright© April 2018, Iran J Allergy Asthma Immunol. All rights reserved

The correlation between the numerical status of Th22 cells and serum level of IL-22 with severity of ulcerative colitis

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, yet its etiology as well as pathogenesis remains poorly understood. There is increasing evidence that aberrant expression of CD4+T lymphocytes plays an essential role in the progression of different pathologies such as UC. This study aimed to evaluate the circulatory frequency of T-helper 22 (Th22), a subset of CD4+ T cells, and serum level of its signature cytokine, IL-22, in patients with UC. Blood samples from 30 patients with UC and 30 controls (n=30) were tested for IL-22 level and circulatory Th22-cell count by ELISA and Flow cytometric analysis, respectively. Our results revealed higher serum level of IL-22 as well as circulatory frequency of Th22 cells in patients with UC compared to those in healthy controls. Notably, effective factors on severity of the disease were age, Th22, IL-22, ESR and CRP. We conclude that elevated circulating Th22 cells and their signature cytokine, IL-22, may be implicated in the pathogenesis of UC. These findings may provide preliminary experimental clues for the development of new therapies for UC and its severity judgment. © February 2018, Iran J Allergy Asthma Immunol. All rights reserved

T helper 22 pathway evaluation in type 1 diabetes and its complications

Abstract A subset of CD4+ T cells named T helper (Th)22 cells play some pathogenic roles in some autoimmune disorders such as type 1 diabetes (T1D). We aimed to study the correlation between the circulatory number of these cells and serum levels of its related cytokines with T1D as well as diabetic complications including metabolic control, atherosclerosis, and nephropathy. Fortynine patients with T1D and 43 healthy controls underwent the assessment of circulatory number of Th22 cells (by flow cytometry), serum level of Th22 related cytokines including Interleukin-22 (IL-22), Interleukin-10 (IL-10), Transforming growth factor-β (TGF-β), Tumor necrosis factor-α (TNF-α) (by ELISA) and carotid intima-media thickness (cIMT) measurement (by doppler ultrasonography). In addition, fasting blood and urine samples were taken to measure levels of hemoglobin A1C, lipid profile, cell blood count (CBC), serum and urine creatinine and urine protein in all participants. Th22 frequency and serum levels of IL-22 and TNF-α in patients were significantly higher than those in controls (p<0.001). Serum levels of IL-10 and TGF-β in healthy individuals were higher than those in patients (p<0.001). None of the Th22 related markers had a significant correlation with diabetic complications. There was only a significant effect of IL-22 on HbA1C variations. Th22 pathway has a significant correlation with T1D but not with its complications of cIMT and Urine Albumin/Creatinine Ratio (UACR). We report that Th22 pathway is not a good prognostic as well as diagnostic marker of early macrovascular complications in T1D. Keywords: Diabetic nephropathy, Diabetes type 1, Intima media thickness

The correlation between the numerical status of Th22 cells and serum level of IL-22 with severity of ulcerative colitis

Abstract Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, yet its etiology as well as pathogenesis remain poorly understood. There is increasing evidence that aberrant expression of CD4+T lymphocytes plays an essential role in the progression of different pathologies such as UC. This study aimed to evaluate the circulatory frequency of T-helper 22 (Th22), a subset of CD4+ T cells, and serum level of its signature cytokine, IL-22, in patients with UC. Blood samples from 30 patients with UC and 30 controls (n=30) were tested for IL-22 level and circulatory Th22-cell count by ELISA and Flow cytometric analysis, respectively. Our results revealed higher serum level of IL-22 as well as circulatory frequency of Th22 cells in patients with UC compared to those in healthy controls. Notably, effective factors on severity of the disease were age, Th22, IL-22, ESR and CRP. We conclude that elevated circulating Th22 cells and their signature cytokine, IL-22, may be implicated in the pathogenesis of UC. These findings may provide preliminary experimental clues for the development of new therapies for UC and its severity judgment. Keywords: Interleukin-22, Th22 cells, Ulcerative coliti

Evaluating Serum Levels of IL-33, IL-36, IL-37 and Gene Expression of IL-37 in Patients with Psoriasis Vulgaris

Serum levels of interleukin (IL)-33, IL-36 and IL-37 have been reported to be up-regulated in various T helper (Th)1/Th17 mediated autoimmune/inflammatory diseases. Although IL-33 and IL-36 expression are increased in skin lesions of patients with psoriasis, their serum levels in such patients have not yet been adequately studied. We aimed to evaluate serum level of IL-33, IL-36 and IL-37 cytokines and IL-37 gene expression in patients with autoimmune/inflammatory disease of psoriasis and to explore their correlation with disease severity. Such evaluation further clarifies disease pathogenesis and may be utilized in clinical practice. 47 patients with psoriasis vulgaris and 47 healthy individuals were included. Serum IL-33, IL-36 and IL-37 levels were measured by Elisa and gene expression of IL-37 measured by real time PCR in all participants. The disease activity was assessed by the psoriasis area and severity index (PASI). Linear Correlation between interleukin measures and PASI score was calculated. Also sensitivity and specificity of such measurements were determined. Serum IL-36 and 37 levels in patients with psoriasis vulgaris were significantly higher than those in healthy controls and positively correlated with disease activity (PASI score). Serum IL-33 levels in patients were equal to those in healthy controls but positively correlated with disease activity. Serum IL-36 levels were significantly higher than serum IL-33 levels. Gene expression of IL-37 levels in patients were higher than healthy controls but was not correlated with disease activity. Serum IL-36 and IL-37 levels are generally increased in psoriasis vulgaris and correlated with disease severity. Therefore, serum IL-36 and IL-37 levels may be markers of treatment and diagnosis of psoriasis. Copyright© April 2018, Iran J Allergy Asthma Immunol. All rights reserved

Evaluating Serum Levels of Pentraxin-3, von Willebrand Factor and C-X-C Motif Chemokine Ligand 13 as Inflammatory Markers of Unstable Angina Pectoris

Unstable angina pectoris (USAP) is a complex condition in which widespread coronary inflammatory processes have important implications for clearer understanding of its pathogenesis and also its treatment. This study aimed at evaluating the diagnostic as well as prognostic value of serum inflammatory markers of pentraxin-3 (PTX-3), Von Willebrand Factor (vWf) and C-X-C Motif Chemokine Ligand 13 (CXCL13) in such patients. Out of sixty-nine patients, thirty-nine had USAP, thirty had stable angina pectoris (SAP), and thirty-nine were healthy controls. For all participants, serum PTX-3, vWf and CXCL13 levels were measured using ELISA. For each patient with USAP, the Thrombolysis in Myocardial Infarction (TIMI) and the scores of Global Registry of Acute Coronary Events (GRACE) were calculated to determine the severity of the disease. We, then, analyzed the relation of PTX-3, vWf and CXCL13 levels with TIMI and GRACE scores in patients with USAP. Serum PTX-3, vWf and CXCL13 levels were significantly higher in USAP group than those in either SAP or control groups (p�0.001). Strong correlation was observed between CXCL13 level and TIMI risk score (p=0.019). In receiver operating characteristic (ROC) curves, area under the curve (AUC) values of PTX3, vWf and CXCL13 for detection of USAP were 0.755, 0.751, and 0.906, respectively. The levels of serum PTX3, vWf and CXCL13 increased in patients with USAP. The notable correlation implied that CXCL13 might be a sensitive and specific biomarker for the diagnosis of USAP as well as its severity. It might also show additional diagnostic values when measured in combination with vWf