Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases

Introduction: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL ?17A) expressing CD4⁺T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung.

Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017.

Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.     

miR-17 and miR-20a Expression in IL-2 Signaling Pathway in Jurkat T Cells

Background: the miR-17-92 cluster is known as an oncogene (oncomiR-1) overexpressed in most cancers. However, recent studies have shown that these miRNAs were downregulated in some cancers. Thus, some or all members of miR-17-92 cluster may have dual activity: apoptosis induction or inhibition. Objectives: For a better understanding of miR-17-92 cluster activities, we focused on the function of mir-17 and mir-20a as two members of miR-17-92 cluster in Jurkat cells activated by phytohemagglutinin (PHA). Materials and Methods: Jurkat cells were stimulated by PHA for 24 h. P-lenti-mico-GFP plasmids containing miR-17 or miR-20a and an empty vector (blank) were transfected into activated Jurkat cells using Lipofectamine 2000 reagent. Cell viability was measured using XTT assay after transfection. Putative targets of these miRNAs were predicted by Targetscan and miRWalk algorithms in JAK/STAT and PI3K/AKT signaling pathways. Then the expression of several putative targets was evaluated by quantitative RT-PCR. Results: Transfection of mir-17 and mir-20a decreased the proliferation in activated Jurkat cells. In silico investigations revealed that mir-17 and mir-20a potentially target JAK1, AKT1 and AKT3. Q-RT-PCR analysis illustrated that these targets were downregulated in Jurkat cells after transfection with miR-17 and miR-20a. Conclusions: According to our findings, it seems that mir-17 and mir-20a expression, two members of miR-17-92 cluster, is dependent on cell condition and cell type; as a result, their ectopic expression in activated Jurkat cells may lead to cell death.     

Human T-Lymphotropic Virus Type I (HTLV-1) Infection among Iranian Blood Donors: First Case-Control Study on the Risk Factors

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is an endemic condition in Northeast Iran and, as such, identification of risk factors associated with the infection in this region seems to be a necessity. All the possible risk factors for HTLV-1 seropositivity among first-time blood donors were evaluated in Mashhad, Iran, during the period of 2011–2012. Blood donation volunteers were interviewed for demographic data, medical history, and behavioral characteristics and the frequencies of risk factors were compared between HTLV-1 positive (case) and HTLV-1 negative (control) donors. The data was analyzed using Chi square and t-tests. Logistic regression analysis was performed to identify independent risk factors for the infection. Assessments were carried out on 246 cases aged 17–60 and 776 controls aged 17–59, who were matched based on their ages, gender, and date and center of donation. Logistic analysis showed low income (OR = 1.53, p = 0.035), low educational level (OR = 1.64, p = 0.049), being born in the cities of either Mashhad (OR = 2.47, p = 0.001) or Neyshabour (OR = 4.30, p < 0001), and a history of blood transfusion (OR = 3.17, p = 0.007) or non-IV drug abuse (OR = 3.77, p < 0.0001) were significant predictors for infection with HTLV-1. Lack of variability or small sample size could be reasons of failure to detect some well-known risk factors for HTLV-1 infection, such as prolonged breastfeeding and sexual promiscuity. Pre-donation screening of possible risk factors for transfusion-transmissible infections should also be considered as an important issue, however, a revision of the screening criteria such as a history of transfusion for more than one year prior to donation is strongly recommended.     

Impact of Hepatitis C Virus Infection on Cognitive Function in Patients With Covert Hepatic Encephalopathy

Background:

Liver cirrhosis has a significant impact on patient’s quality of life and socioeconomic status and is associated with increased susceptibility to vehicle accidents and falls.

Objectives:

This study was conducted to evaluate cognitive function in patients with cirrhosis.

Patients and Methods:

All subjects, who underwent transient elastography (TE) between March 2014 and August 2014 in Shariati outpatient clinic, Tehran, Iran, were enrolled in the study. The diagnosis of cirrhosis was made based on clinical and laboratory findings and liver stiffness measurement (LSM) values > 14. Wechsler Memory Scale (WMS) and simple visual reaction time (RT) were the neuropsychiatric tests used to assess cognitive function, in all subjects.

Results:

A total of 37 cirrhotic patients and 37 matched controls were included. Patients with cirrhosis had significantly lower mean quotient (MQ) score, compared with controls (91 ± 18.2 vs. 114.6 ± 17.5, P <0.001). All of WMS subscales, except associate learning, showed statistically significant differences between the two groups. Reaction time was more prolonged in patients with cirrhosis, compared with controls. Cognitive function of hepatitis C virus (HCV) patients was significantly impaired, with respect to logical memory, visual reproduction and MQ score, compared to other underlying causes of cirrhosis (P = 0.01, P = 0.04, and P = 0.01, respectively)

Conclusions:

Our results suggested that neuropsychiatric and cognitive problems must be considered in the management of covert hepatic encephalopathy (HE) patients, especially in patients with HCV infection. The WMS and simple visual RT tests are useful methods for the early diagnosis of covert HE.     

Detection of Hepatitis B Virus Covalently Closed Circular DNA in the Plasma of Iranian HBeAg-Negative Patients With Chronic Hepatitis B

Background:

Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a marker of HBV replication in the liver of patients infected with HBV.

Objectives:

This study aimed to investigate the association between the presence of cccDNA in the plasma samples of Iranian treatment-naive patients with chronic hepatitis B infection and HBV viral load and HBsAg levels.

Patients and Methods:

From April 2012 to May 2015, 106 treatment-naive patients with chronic hepatitis B infection were enrolled in this cross-sectional study. The HBsAg titer was measured by the Roche HBsAg II assay on the Cobas e411 system, and HBV DNA quantitation was performed using the COBAS TaqMan 48 kit. Real-time polymerase chain reaction was performed for the detection of HBV cccDNA.

Results:

The mean (SD) age of the patients was 41.1 ± 12.4 years (range, 20 - 62 years). From a total of 106 study participants, 67 (63.2%) were males. The HBV cccDNA was detected in plasma specimens in 19 (17.9%) out of the total 106 patients, and a significant relationship was found between the presence of cccDNA in plasma sample of males (23.9%) and females (7.7%) (P = 0.039). Also, a significant correlation was found between the presence of cccDNA in plasma sample of the patients and HBV viral load level (P < 0.0001) and HBsAg titer (P = 0.0043).

Conclusions:

This study showed that cccDNA can be detected in the plasma specimen of 17.9% of Iranian treatment-naive patients with chronic hepatitis B infection. Therefore, designing prospective studies focusing on the detection of cccDNA in these patients would provide more information.     

Efficacy of Prolonged Treatment With Pegylated Interferon (Peg-IFN) and Ribavirin in Thalassemic Patients With Hepatitis C Who Relapsed After Previous Peg-IFN-Based Therapy

Background:

Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.

Objectives:

In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.

Patients and Methods:

In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.

Results:

For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P = 0.03) and undetectable HCV RNA level at week 12 (P < 0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.

Conclusions:

The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen.     

Subclinical entheseal involvement in patients with rheumatoid arthritis

BackgroundEnthesopathy is a common feature of Spondyloarthritis (SpA) but can also be found in rheumatoid Arthritis (RA). Recognizing enthesopathy could be challenging because of low sensitivity and specific clinical testing. To detect enthesopathy, The European League Against Rheumatism (EULAR) recommends magnetic resonance imaging (MRI) or ultrasonography (US).Aim of the workTo investigate the frequency and distribution of entheseal involvement in RA patients and its relation to disease activity.Patients and methods100 RA patients with any symptom in foot and ankle were enrolled. Disease activity score (DAS28), Visual analogue scale (VAS), Health assessment questionnaire-Disability index (HAQ-DI) and Glasgow Ultrasound Enthesitis Scoring System (GUESS) were assessed.ResultsThe mean age of patients was 44.1 ± 12.2 years, disease duration was 7 ± 5.8 years and 86% were females. The mean DAS28 score was 4.3 ± 1.2 and GUESS score was 7.2 ± 4.2; all patients had variable degrees of enthesitis: 30% of patients had mild enthesitis, 42% had moderate enthesitis and 28% had marked enthesitis. GUESS was significantly higher in patients with moderate (7.8 ± 4.9) and high (7.2 ± 3.2) disease activity than in patients with low disease activity (5.2 ± 3.9) and those in remission (6.5 ± 1.9) (p = 0.015). HAQ, Age and ESR significantly correlated with GUESS score (r = 0.19, p = 0.049; r = 0.23, p = 0.023; r = 0.33, p = 0.001 respectively).ConclusionSubclinical enthesitis is remarkable in RA patients. Quadriceps tendon enthesis was mostly affected. Enthesitis is significantly related to age, ESR and HAQ. The presence of enthesitis in RA may represent a potential marker for disease activity.