Different Gene Expressions of Alpha and Beta Glucocorticoid Receptors in Asthmatics.

The response to glucocorticoids (GCs) therapy classifies severe refractory asthma (SRA) and mild asthma, so the glucocorticoid receptors (GCRs) gene expression may be involved in SRA pathogenesis. Thus, it is aimed to compare the expression levels of two GCR isoforms (GCRα and GCRß) in SRA, mild asthmatics, and healthy controls. Total RNA was isolated from the peripheral blood mononuclear lymphocytes of 13 SRA patients, 14 mild asthma patients and 30 healthy volunteers. The expression levels of GCR isoforms were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The expression level of GCR isoforms did not show any significant difference between the cases/control groups. However, the relative expression analysis between asthma/control, SRA/control and SRA/asthma groups was in the order of 0.933, 0.768 and 0.823 for GCRα and 0.697, 1.014 and 1.454 for GCRß, respectively. Also, the expression fold change of GCRα/GCRß in asthma, SRA and control groups was 786.88, 445.72 and 588.13, respectively. The GCRα and GCRß isoforms did not show any correlation in SRA; but they had significant correlation in both healthy volunteers (r = 0.490, P = 0.007) and mild asthmatics (r = 0.786, P = 0.001). Also, the GCRα expression level had significant inverse correlation with age in SRA (r = -0.709, P = 0.007). Glucocorticoid receptors are related to, but not directly responsible for GC resistance. Since the GCRα/GCRß expression ratio decreased in SRA, studies are needed to assess its value in diagnosing GC resistance.

The Study of IL-10 and IL-17A Genes Expression in Patients with Different Stages of Asthma: a Case-Control Study.

BACKGROUND: Asthma is considered as a complex disorder in which genetics and environment play crucial role in its susceptibility. In addition to the huge financial costs that significantly reduce the quality of life of the patients and their families, it causes high prevalence of lung diseases. Finding contributing new genetic factors involved in early diagnosis or progression of asthma can provide novel approaches for treatment or managing of asthma. In the present study, the potential role of two key cytokines of IL-10 and IL-17A was investigated in asthma pathogenesis. MATERIALS AND METHODS: Using real-time PCR technique, we analyzed the expression levels of target genes in two groups of mild and severe asthma patient in comparison with healthy individuals. RESULTS: In comparison with control population, obtained data showed 4 and 7-fold down-regulation of IL-17A in the group of mild and severe asthma, respectively. Down-regulation of IL-17A showed a significant correlation with progression of asthma severity. While IL-10 showed up to 10-fold down-regulation in the group of severe asthma, its expression level was not correlated with severity of asthma. CONCLUSION: Obtained data revealed that deregulation IL-10 and IL-17A have potential to play crucial role in pathogenesis and prognosis of asthma. Observed down-regulation of these cytokines in blood cells suggests their usefulness as a marker in diagnosis of asthmatic types in patients.

Cellular immune response in MDR-TB patients to different protein expression of MDR and susceptible Mycobacterium tuberculosis: Rv0147, a novel MDR-TB biomarker.

Tuberculosis (TB) is a crucial public health problem with prevalence of multidrug resistant (MDR) rising. An accurate TB biomarker is urgently needed to monitor the response to treatment in patients with MDR tuberculosis. To analyze interaction between selected MDR-TB purified protein and immune cells, dendritic cells from MDR-TB patients and healthy subjects were stimulated by 55KDa protein fractions (Rv0147). The purified proteins identified by proteomic techniques (two-dimensional gel electrophoresis, mass spectrometry) and peptide sequences are known to bind a MHC class I alleles which are extracted from the Immune Epitope Database and Analysis Resource database ( www.iedb.org ). T cells were isolated from PBMC by negative selection and cells were cultured in RPMI-1640 at 37 °C and 5% CO2. Cell culture was assayed for cytokine IL-10 and INF-γ by ELISA. We found that INF-γ production was significantly (335 ± 35.5 pg/ml, P ˂ 0.05) upregulated after protein candidate (Rv0147) stimulation by dendritic cells from MDR-TB patients, whereas IL-10 production was greatly reduced compared with production in healthy subjects (212 ± 9.94 pg/ml, P ˂ 0.05). In fact, the purified protein, Rv0147, stimulated dendritic cells from MDR-TB patients, failed to produce IL-10 and directly stimulates INF-γ production by T cells. These results suggest that the purified protein, Rv0147, may stimulate Th1 type protective cytokine response in MDR-TB patients but not in normal subjects. The production of INF-γ but not IL-10 in the presence of purified protein, Rv0147, may be shifted to Th1 responses in MDR-TB patients and supports its potential as protein vaccine candidates against TB.

The Expression of STAT3 and STAT5A Genes in Severe Refractory Asthma.

BACKGROUND: Despite being a high burden disorder, the pathogenesis of severe refractory asthma (SRA) is poorly understood. There are some evidences for the involvement of members of the signal transducer and activator of transcription (STAT) family, including STAT3 and STAT5a. Our study aimed to evaluate the gene expression of STAT3 and STAT5a in asthma and SRA to establish if there is an association. MATERIALS AND METHODS: Using quantitative real-time polymerase chain reactions (qRT-PCR), the transcript levels of STAT3 and STAT5a were evaluated in peripheral blood mononuclear lymphocytes (PBML) isolated from 13 patients with SRA, 14 with mild asthma, and 30 healthy volunteers. RESULTS: There were no significant differences in STAT3 transcript levels between study groups. There was however a significant difference in STAT5a transcript levels between cases and controls (p-value=0.03). In comparison to healthy controls, the levels of STAT5a were notably lower in patients with mild asthma and significantly least in those with SRA. CONCLUSION: Our study found no appreciable association between STAT3 gene expression and either mild asthma or SRA. However, the STAT5a down regulation in asthmatics and especially SRA is a notable finding which denotes on association between STAT5a and different level of asthma.

What Do We Know about Anthracofibrosis? A Literature Review.

Recently, the significance of anthracosis in the tracheobronchial tree, lung parenchyma, and even non-respiratory organs has been postulated and discussed in association with other diseases, especially tuberculosis. We reviewed the current literature by using the following key words in Medline/PubMed, Embase, and Google Scholar databases: anthracosis, anthracofibrosis, anthracotic bronchitis, biomass fuels, and mixed-dust pneumoconiosis. The bibliographies of eligible papers were also reviewed for further relevant articles. A total of 37 studies were assessed. The content of these studies was then divided into specific categories. Considering the pathogenesis, along with histopathological, radiological, and bronchoscopic results regarding anthracotic lesions, we suggest these findings be defined as "ANTHRACOSIS SYNDROME". For the first time, we describe a syndrome involving black pigmentation, which was previously thought to involve only the tracheobronchial tree. Until recently, it was not considered to be a single syndrome with different sites of involvement.

Performance assessment of Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score II in a referral respiratory intensive care unit in Iran.

BACKGROUND/PURPOSE: Nowadays, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems have drawn much attention for the evaluation and prediction of disease process in patients admitted to intensive care units (ICUs). To use these scoring tools, their predicting power must be initially validated for the target patients. This study was conducted to evaluate the performance of these two scoring systems in an ICU for respiratory diseases in Iran. MATERIAL AND METHODS: All records of patients admitted during a 1-year period were retrospectively reviewed, and the APACHE II and SAPS II scores were calculated accordingly. Information gathering was performed using a questionnaire. RESULTS: A total of 415 records were used. The mean age of patients was 49.28 ± 0.94 years. Using receiver operating-characteristic curve, cutoff points for 80% sensitivity and specificity of mortality prediction for APACHE and SAPS scores were 13.5 and 27.5, respectively. Calibration and discrimination studies indicated an acceptable status for both scales, but APACHE II scoring system seemed to show rewarding outcomes. CONCLUSION: Results indicate that APACHE II scoring system can be considered as a reliable method for predicting mortality in our referral respiratory ICU.

Fc-Gamma Receptor 3B Copy Number Variation Is Not a Risk Factor for Behçet's Disease.

Behçet's disease (BD) is an immune-mediated systemic vasculitis associated with HLAB51. Other gene associations are likely and may provide further insight into the pathogenesis of this disease. Fc-gamma receptors play an important role in regulating immune function. Copy number variation (CNV) of the Fc-gamma receptor 3B (FCGR3B) gene is associated with other inflammatory conditions and may also play a role in BD. The aim of this study was to determine whether CNV of the FCGR3B gene is associated with BD or its clinical features. FCGR3B copy number was determined for 187 Iranian patients and 178 ethnicity-matched controls using quantitative real-time PCR. The genotype frequencies were comparable in both BD patients and controls. The odds ratio for low copy number (<2CN) was 0.6 (P = 0.16) and the odds ratio for high copy number (>2CN) was 0.75 (P = 0.50). There was no association found between high or low CN of the FCGR3B gene and BD or its clinical features in this Iranian population. We are the first to report this finding which, when looked at in the context of other genetic studies, gives us further insight into the complex pathogenesis of BD.

Association of interleukin-2, interleukin-4 and transforming growth factor-beta gene polymorphisms with Behcet's disease.

Behçet's disease (BD) is a chronic immune-mediated disease, characterised by oral and genital lesions and ocular inflammation. As cytokines seem to have important roles in the pathogenesis of BD and production of cytokines could be affected by genetic polymorphisms, this study was performed to investigate gene polymorphisms of a number of cytokines in the patients with BD in comparison with control subjects. One hundred and fifty patients with BD were enrolled in this study. Interleukin (IL)-2 (-330, +166), IL-4 (-1098, -590, -33), IL-10 (-1082, -819, -592), IL-12 (-1188), IFN-γ (5644), transforming growth factor (TGF)-ß (codon 10, 25), and IL-4RA (+1902) typing were performed by polymerase chain reaction with sequence-specific primers. In the patients with BD, there were significantly increased frequency of IL-2 (-330) GG genotype (p<0.001), IL-4 (-33) CC genotype (p<0.001), and TGF-ß (codon 10) CC genotype (p=0.004). Meanwhile a significant decrease in the frequency of IL-4 (-33) TC genotype (p<0.001) was detected in the patient group in comparison with normal controls. The genotype CC of TGF-ß at codon 10 was also significantly overrepresented in the patient group (p=0.004). Haplotype frequencies of IL-4 (-1098, -590, -33) showed that the frequency of TTC haplotype was significantly increased in the patients (p<0.001), whereas TTT haplotype was significantly decreased in this group of patients (p<0.001). There was not any significant difference in allele and genotype frequencies of IL-10, IL-12, IFN-γ, and IL-4RA between patient and control groups. Cytokine single nucleotide polymorphisms could play a role in the pathophysiology of BD. The results of this study could suggest a tendency towards higher production of IL-2 and lower production of IL-4 in the patients with BD.

Occult hepatitis B among chronic liver disease patients.

OBJECTIVE: Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Diagnosis of occult HBV infection requires sensitive HBV-DNA polymerase chain reaction (PCR) assay. Occult hepatitis B is a new entity and the prevalence of it and its clinical importance has not been investigated yet in Iran. The aim of this study is to investigate the prevalence and clinical importance of occult hepatitis B among chronic liver disease patients in Iran. METHODS: We studied 35 consecutive paraffin-embedded liver tissues cases referred to Research Center for Gastroenterology and Liver Diseases, Tehran, Iran during the year 2001 to 2002 for liver biopsy due to its elevation of alanine aminotransferase (ALT) levels for more than 6 months. Liver biopsies were reviewed and HBV-DNA and HBsAg and Hepatitis B core antigen were assayed in liver tissue by PCR and immunohistochemistry (IHC). RESULTS: Our patients with chronic liver disease (CLD) included hepatitis C (77.1%), cryptogenic liver disease (20%), and autoimmune hepatitis (2.9%). Histologically, chronic hepatitis, cirrhosis and non-specific changes were reported. Hepatitis B virus-DNA was detectable in 8 (22%) patients; however, IHC was negative in all. CONCLUSION: Occult hepatitis B is relatively frequent among patients with CLD in Iran. It maybe associated with more advanced liver pathology (cirrhosis) and more aggressive clinical course (decompensated cirrhosis). Occult HBV infection causes strong suppression of viral gene expression.