Inflammatory and T Helper 17/ Regulatory T Cells Related Cytokines Balance in Cutaneous Lupus Erythematosus (CLE).

The cutaneous lupus erythematosus (CLE) is a common manifestation among systemic lupus erythematosus (SLE) patients. Malar rash and discoid lupus (DLE) are in the category of acute and chronic CLE, respectively. The pathogenesis of CLE is multifactorial, and cytokine imbalances contribute to immune dysfunction and the induction of organ damage. Many aspects of cytokine dysregulation are still unclear in SLE and in particular CLE. Therefore, we concurrently measured the inflammatory [Tumor necrosis factor-alpha (TNF-α) and Interleukin (IL)-6)], T helper (Th)-17 (IL-17 and IL-23) and regulatory T cells [Transforming growth factor-beta (TGFß) and IL-10)]-related cytokines in patients with CLE (patients with malar rash and/or DLE) and compared them with SLE patients and healthy individuals (n=25 in each group, a total of 75 patients). The serum levels of cytokines were assessed by Enzyme-Linked Immunosorbent Assay (ELISA) method. IL-6 cytokine was significantly higher in SLE, DLE, and malar rash patients compared to those in healthy controls (p=0.025) and in patients with arthralgia (p=0.038), and gastrointestinal involvement (p=0.048). IL-17 was significantly higher in malar rash patients compared to normal individuals (p=0.023), SLE (p=0.008) and DLE patients (p=0.019) and in patients with oropharyngeal ulcer (p=0.05) but, IL-23 was significantly higher only in DLE patients than healthy controls (p=0.019). In conclusion, inflammatory cytokines such as IL-6 involved in inflammation and differentiation of Th17 cells are probably responsible in part for Th17 activity in CLE. IL-17, IL-23, and IL-6/IL-6R (IL-6 receptor) inhibitors may be good treatments for CLE patients. So targeting these cytokines activity pathways can improve the CLE treatment strategy and may open a novel guideline for SLE and CLE treatment.

Interleukin-27 gene variant rs153109 is associated with enhanced cytokine serum levels and susceptibility to Behçet's disease in the Iranian population.

Behcet's disease (BD) is a systemic vasculitis, characterized by recurrent oral aphthous, genital ulcers, ocular lesions, and other organ involvement. Interleukin (IL)-27 with its pro- and anti-inflammatory effects might be an important effective cytokine in this disease. The aim of this study was to investigate the association of IL-27 serum concentration and a single-nucleotide polymorphism (SNP) rs153109 (-964 A > G) with the risk and clinical features of the patients with BD. IL-27 Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the IL-27 serum levels were measured using enzyme-linked immunosorbent assay (ELISA). It is shown that AG, GG, and AG + GG genotypes, as well as G allele of rs153109, can significantly increase the risk of BD in total and in male individuals. Significantly higher frequencies of AG and GG genotypes and G allele were observed in total and male patients with an active form of BD. AG and GG genotypes were associated with joint (p = 0.046) and vascular (p = 0.02) involvement. The frequency of the G allele was higher in all patients, as well as in female patients with vascular involvement (p = 0.02). Serum cytokine analysis indicated an increased level of IL-27 in BD patients compared to healthy subjects (p = 0.038). Additionally, a higher level of IL-27 was detected in patients carrying the rs153109 GG genotype (p = 0.04) and those with renal (p = 0.009) and skin (p = 0.05) involvement. In conclusion, this study underscores the involvement of IL-27 rs153109 variants and increased serum level in BD susceptibility and pathogenesis.

Predominant role of innate pro-inflammatory cytokines in vitiligo disease.

Vitiligo is a skin disorder with melanocyte destruction and an autoimmune basis. Given the importance of cytokines in autoimmunity, we aimed to find the cytokine profile of innate and adaptive immunity in vitiligo patients, and correlate them with clinical parameters. The serum levels of innate immunity [interleukin(IL)-1α, IL-1ß, IL-6, IL-8, IL-12, IL-15 and tumor necrosis factor (TNF)-α] and T helper(Th)1 [IL-2, interferon (IFN)-γ, TNF-ß], Th2 (IL-4, IL-5, IL-10, IL-13) and Th17 (IL-17, IL-23) cytokines in 44 vitiligo patients were measured by multiplex cytokine assay and compared with 44 healthy subjects. All innate immunity (p < 0.04), Th1 (p < 0.01), Th2 (p < 0.05) and Th17 (p < 0.001) cytokines were higher in patients than controls. Total summation levels of innate immunity and adaptive immunity cytokines showed a remarkable up-regulation in the patients (p < 0.0001). The ratio of innate immunity to Th1 (p = 0.03), Th2 (p = 0.01) and Th17 (p = 0.03) cytokines was significantly higher in patients vs. controls. We found significant higher ratio of Th1 to Th2 cytokines and TNF-ß elevated levels in patients with a family history of autoimmunity (p < 0.05). IL-4 and IL-13 (p < 0.04) levels were lower in patients with amelanotic hair. Increased IL-10 level was observed in patients with stable disease (p = 0.02).In conclusion, the profile of cytokines in patients showed a dominant role of innate immunity pro-inflammatory cytokines in vitiligo, which suggests the potential of targeting these cytokines for vitiligo treatment. While a higher ratio of Th1/Th2 cytokines was observed in the patients, association of decreased Th2 cytokines with disease complications suggests a protective role for Th2 pathway.

Interleukin-17 production by CD4+CD45RO+Foxp3+ T cells in peripheral blood of patients with atherosclerosis.

INTRODUCTION: T regulatory cells (Tregs) are known as immunoregulatory cells that are reduced in atherosclerosis. Tregs are a part of crosstalk between the immune system and lipoprotein metabolism, both of which are involved in atherosclerotic processes. Depletion of Tregs leads to impaired clearance of low density lipoprotein (LDL), and intracellular cholesterol homeostasis affects Treg cell development. Furthermore, the atherosclerotic environment affects the Treg cells' phenotype and plasticity. Plasticity between Tregs and Th17 cells has been a matter of investigation lately. We investigated the frequency of interleukin-17 (IL-17)-producing Tregs in the peripheral blood of patients with atherosclerosis. MATERIAL AND METHODS: We studied 10 non-diabetic patients with significant coronary artery disease (CAD) as the patient group, and seven non-diabetic individuals with normal coronary angiography/insignificant CAD as the control group. Peripheral blood mononuclear cells were stained with fluorescent antibodies to detect CD4, CD45RO, IL-17, and Foxp3 expression both before and after stimulation with PMA/Ionomycin. Cell enumeration was performed using flowcytometry and analysed using Mann-Whitney test. RESULTS: CD4+IL-17+Foxp3+ and CD4+IL-17+Foxp3- subsets showed higher frequencies in patients than in controls both before (p = 0.0031, p = 0.033, respectively) and after stimulation (p = 0.0027 and p = 0.0013, respectively). Interestingly, CD4+IL-17+Foxp3+ cells were almost exclusively CD45RO+ with a much higher frequency in patients than in controls (p = 0.0027, p = 0.0007). After stimulation, the frequency of CD4+CD45RO+IL-17+Foxp3+ lymphocytes increased to a greater extent in patients (p < 0.0001) than in controls. CONCLUSIONS: Interleukin-17 production by an intermediate population with an activated Treg phenotype in our patients may point to the population heterogeneity or plasticity in Tregs during atherosclerotic inflammation.

Prevalence of transfusion transmitted virus infection in hemodialysis patients and injection drug users compared to healthy blood donors in isfahan, iran.

Introduction. The pathogenicity and transmission routes of Transfusion Transmitted Virus (TTV) remain unclear. The aim of this study was to determine the prevalence of TTV in hemodialysis patients, injecting drug users (IDUs), and healthy blood donors, in Isfahan, Iran. Method. In a case-control study, a total of 108 subjects were put into three groups namely Group I, 36 hemodialysis patients; Group II, 36 IDUs; and Group III, 36 healthy blood donors as the control group. A 5 ml blood sample was collected from each subject in an EDTA-containing tube. Samples were tested for TTV DNA by means of real-time polymerase chain reaction (PCR). Results. The mean age was 38.7 ± 14.7 years. Seventy-one subjects (66%) were male. Of the108 cases, 30 (27.8%) were TTV positive and 78 (72.2%) were TTV negative. The prevalence of TTV in IDUs [21 (58%)] was significantly higher than in the other groups [group I: 6 (17 %) and group III: 3 (8%)] (P < 0.0001). Conclusion. The prevalence of TTV in IDUs is significantly higher than in both hemodialysis patients and general population in Isfahan, Iran. It seems necessary to take serious measures to reduce the risk of TTV transmission to IDUs' close contacts and health care providers.

Prevalence and Risk Factors of HIV, Syphilis, Hepatitis B and C Among Female Prisoners in Isfahan, Iran.

BACKGROUND: Female prisoners are at risk of acquiring sexually transmitted infections (STIs). There has been no previous study regarding the epidemiological status of STIs among female prisoners in Isfahan, central Iran. OBJECTIVES: The aim of this study was to investigate the prevalence and risk factors of the aforementioned infections among women incarcerated in the central prison, Isfahan, to determine appropriate prevention measures. PATIENTS AND METHODS: In a cross-sectional study, all of the 163 women incarcerated in the central prison, Isfahan in 2009, were voluntarily enrolled by the census method. After completing a checklist consisting of demographic, social, and risk factors, a 5ml blood sample was taken from each individual. The sera were analyzed for markers of the hepatitis B virus (HBV; HBsAg, HBsAb, HBcAb), hepatitis C virus (HCV; HCV antibodies), human immunodeficiency virus (HIV; HIV antibodies), and syphilis (RPR). Confirmatory tests were performed on HCV antibody-positive cases. RESULTS: The mean age of the participants in the study was 34.54 ± 11.2 years old, 94.3% of these women were Iranian, and many of them had only a primary level of education. The prevalence of HBsAg, HBcAb, HBsAb, and HCV antibodies were; 1.2%, 7.4%, 12.9% and 7.4% respectively. No positive RPR or HIV antibodies were detected. CONCLUSIONS: A significant relationship was seen between the HCV antibody, drug injection and illegal sex in the women, and also between HBc-Ab and drug injection. Regular screening, educational programs, and facilitation of access to suitable treatment care should be widely implemented in the prison population. Testing for immunity against HBV should be considered on admission, and afterwards vaccination of all prisoners and an appropriate preventative approach should be applied.

Identification of Patients with Hepatitis C Virus Infection in Persons with Background of Intravenous Drug Use: The First Community Announcement-based Study From Iran.

OBJECTIVES: Injection drug use plays the most important role in transmission of hepatitis C. In Iran, surveys have been conducted on various high risk groups but this is the first announcement based study for hepatitis C virus HCV prevalence among cases with history of intravenous drug using (IVDU) in the country. METHODS: The announcement-based detection and follow-up of patients with anti-HCV positive project in volunteers with history of intravenous drug using was conducted in Isfahan province. At the first step, six focus groups were conducted and 2 pilot studies were carried out in two cities to design the main study. Comprehensive community announcement was done in all of public places and for physicians. The volunteers were invited to Isfahan reference laboratories and the serum samples were sent to Infectious Diseases Research Center Laboratory in standard conditions and HCV-Ab was tested by ELISA method. RESULTS: In this study, 1,747 individuals that are estimated 50% of all expected intravenous drug users in the community were presented themselves. The most important reasons of success in recruiting volunteers in this study were the perfect propaganda, appropriate cooperation of lab staffs, continuous evaluation and good cooperation in Isfahan province administrations. HCV-Ab was detected in 34% of them and the HCV-Ab positives were sent for further follow-up procedures including confirmatory test, education, and treatment. CONCLUSIONS: In spite of some limitations to select real cases, this study was considered as a successful experience. Compared to the surveys in Iran on HCV prevalence in intravenous drug users, the results of this study, which was based on volunteers by announcement seems to be noteworthy.

Hepatitis C virus infection in patients with hemophilia in Isfahan, Iran.

OBJECTIVES: Patients with hereditary bleeding disorders are at risk of viral infection such as hepatitis C due to frequent transfusion of blood and blood products. This study aimed to determine the prevalence of hepatitis C and associated risk factors in hemophilic patients in Isfahan, the second big province in Iran. METHODS: In a descriptive study, patients with hemophilia in Isfahan province were enrolled. A questionnaire, including demographic and risk factors of hepatitis C was completed through a structured interview with closed questions by a trained interviewer for each patient and HCV-Ab test results were extracted from patient records. RESULTS: In this study, 232 of 350 patients with hemophilia A and B (66%) were positive for hepatitis C. Based on Multivariate Logistic Regression model, no independent risk factor was found. CONCLUSIONS: Prevalence of hepatitis C in patients with haemophilia A and B in Isfahan is high. Since no independent risk factor for hepatitis C disease was found in this high risk group, it can be concluded that multitransfusion is the only predictor for hepatitis C.

Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran.

BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23(rd) 2009 to February 20(th) 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific.

Clinical features of novel 2009 influenza A (H1N1) infection in Isfahan, Iran.

BACKGROUND: During August 2009, novel H1N1 influenza virus began causing illness in Isfahan. Since rates of hospitalization and mortality due to the disease have varied widely in different countries, we described the clinical, radiologic, and demographic features of H1N1 hospitalized patients in a hospital in Isfahan. METHODS: This cross-sectional study was conducted in Alzahra Hospital during September 2009 to February 2010. Totally, 216 patients with confirmed, probable, or suspected cases of 2009 influenza A (H1N1) were admitted. RESULTS: Most patients were women (50.5%). Mean age of patients was 26.6 ± 19.5 years. The most common complains on admission were respiratory symptoms (91.6%, n= 198), fever (88.4%, n = 191), myalgia (65.7%, n = 142). In addition, 120 patients (56%) had at least one underlying medical disorder. Thirty-six patients (16.7%) died. Mortality was higher in children under 5 years old (10/36, 10%) and female cases (63.9% of died patients). Predicting variables affecting mortality were intensive care unit (ICU) admission and procalcitonin (PCT) > 0.5. Antiviral treatment was prescribed for 200 (92.5%) of the 216 patients. CONCLUSIONS: Based on the findings of the present study, novel H1N1 influenza is highly prevalent among the youth. Moreover, it causes a relatively high morbidity rate. Therefore, people need to be encouraged to have vaccination against 2009 H1N1. Early diagnosis and treatment is related to less admission and shorter duration of hospitalization.

Hepatitis D virus infection in Isfahan, central Iran: Prevalence and risk factors among chronic HBV infection cases.

BACKGROUND: Hepatitis D virus (HDV) is dependent on hepatitis B virus (HBV) infection. Acute infection with HDV can occur simultaneously with acute HBV infection or be superimposed onto a chronic HBV infection. OBJECTIVES: This study aimed to identify cases of HDV and determine its prevalence in patients with chronic HBV infection for the first time study in Isfahan, central Iran. PATIENTS AND METHODS: In a cross-sectional study in 2009, 346 who had been diagnosed for at least 6 months with chronic HBV were enrolled consecutively. Anti-HDV was measured by ELISA in the serum of these patients. RESULTS: The study included 245 males (70.8%) and 101 (29.2%) females with a mean age of 39 ± 12.4 years. Anti-HDV was present in 8 (3.5%) HBe antibody-positive patients (p = 0.36) and in 2 (2.3%) HBe antigen-positive cases (p = 0.68). No association was found between hepatitis D and probable risk factors. CONCLUSIONS: This study demonstrates that the prevalence of HDV infection is higher in patients who are positive for HBeAb compared those who are HBeAg-positive. Therefore, most HDV antibody-positive cases in Isfahan are HBV/HDV superinfections but not coinfections.