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The pathogenesis of idiopathic pulmonary fibrosis (IPF) is quite similar to that of cancer pathogenesis, and several pathways appear to be involved in both disorders. The mammalian target of the rapamycin (mTOR) pathway harbors several established oncogenes and tumor suppressors. The same signaling molecules and growth factors, such as vascular endothelial growth factor (VEGF), contributing to cancer development and progression play a part in fibroblast proliferation, myofibroblast differentiation, and the production of extracellular matrix in IPF development as well. The expression of candidate genes acting upstream and downstream of mTORC1, as well as Vegf and low-density lipoprotein receptor related protein 1(Lrp1), was assessed using specific primers and quantitative polymerase chain reaction (qPCR) within the lung tissues of bleomycin (BLM)-induced IPF mouse models. Lung fibrosis was evaluated by histological examinations and hydroxyproline colorimetric assay. BLM-exposed mice developed lung injuries characterized by inflammatory manifestations and fibrotic features, along with higher levels of collagen and hydroxyproline. Gene expression analyses indicated a significant elevation of regulatory associated protein of mTOR (Raptor), Ras homolog enriched in brain (Rheb), S6 kinase 1, and Eukaryotic translation initiation factor 4E-binding protein 1 (4Ebp1), as well as a significant reduction of Vegfa, Tuberous sclerosis complex (Tsc2), and Lrp1; no changes were observed in the Tsc1 mRNA level. Our findings support the elevation of S6K1 and 4EBP1 in response to the TSC/RHEB/mTORC1 axis, which profoundly encourages the development and establishment of IPF and cancer. In addition, this study suggests a possible preventive role for VEGF-A and LRP1 in the development of IPF. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is the main manifestation of systemic Lupus Erythematosus (SLE). MicroRNAs (miRNAs) and autoantibodies could be suitable candidate biomarkers of LN. This study evaluates the expression of circulating miR-148a and miR-126 along with anti-dsDNA, anti-C1q, and anti-C3b autoantibodies in SLE patients with LN (SLE + LN). 30 women with SLE, 30 women with SLE + LN, and 25 women as healthy controls (HCs) were enrolled in this study. The plasma expression of selected miRNAs was evaluated by real-time PCR. The serum level of anti-dsDNA, C1q, and C3b antibodies was measured by the ELISA. The expression of miR-148a was significantly increased in SLE and SLE+LN groups compared with the control group. No significant difference was found in the expression of miR-126 among the groups. The frequency of autoantibodies was significantly higher in the SLE + LN group than SLE. The Higher levels of circulating miR-148a in the SLE samples compared with the HCs suggest that this miRNA could be a reliable biomarker for SLE patients (with or without LN). Also, autoantibodies against dsDNA, C1q, and, C3 could be used for the prediction of SLE nephritis, independently. However, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis)RA(pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-ß, IL-6, TNF-a, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikßa and pIkßa) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-ß, IL-6, TNF-a, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikßa and pIkßa by western blot. The baseline expression of IL1-ß, IL-6, TNF-a, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1ß, IL-6, TNF-a, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkßa in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients. [ABSTRACT FROM AUTHOR]

Lupus Nephritis (LN) in patients with Systemic Lupus Erythematosus (SLE) is one of the most serious and prevalent manifestations. The procedure of renal biopsy is harmful and accompanied by potential hazards. Therefore, introducing reliable biomarkers to predict LN is exceedingly worthwhile. In the present study, we compared the diagnostic values of circulating autoantibodies against dsDNA, C1q, C3b, SSA, SSB, and Sm alone or in combination to predict LN. This study evaluated the abovementioned autoantibodies in 40 healthy controls (HCs) and 95 SLE patients with different kidney involvements, including absent (n = 40), inactive (n = 20), and active (n = 35) LN using EIA method. The frequency and odds ratio of anti-dsDNA (71.4%, OR = 4.2), anti-C1q (62.9%, OR = 5.1), and the simultaneous existence of anti-C1q and anti-dsDNA (51.4%, OR = 6) antibodies were significantly higher in the active LN group compared with both inactive and absent LN groups. Moreover, the levels of anti-C1q and anti-dsDNA antibodies positively correlated with disease activity in patients with SLE. The prevalence of these autoantibodies was associated with the severity of LN biopsies. These data suggest that anti-C1q and anti-dsDNA antibodies and also their simultaneous presence may be valuable diagnostic biomarkers for LN prediction in patients with SLE. [ABSTRACT FROM AUTHOR]

Melanoma antigen gene A3 (MAGE‐A3) is one of the most immunogenic cancer testis antigens and is common in various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE‐A3 in 153 prostate tissue samples including prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high‐grade prostatic intraepithelial neoplasia (HPIN). Increased both nuclear and cytoplasmic expression of MAGE‐A3 was significantly found in PCa tissues compared with both HPIN and BPH tissues (nuclear expression at p = 0.011, and cytoplasmic expression at p = 0.034; for both comparisons p < 0.0001, respectively). A significant correlation was observed between higher nuclear and cytoplasmic expressions of MAGE‐A3 with Gleason score (p < 0.0001 and 0.006, respectively). Increased expression of MAGE‐A3 was associated with shorter biochemical recurrence‐free survival (BCR‐FS) and disease‐free survival (DFS) of patients (p = 0.042 and = 0.0001, respectively). In multivariate analysis, nuclear expression of MAGE‐A3 and Gleason score (≤7 vs >7) was independent predictors of the DFS (both; p = 0.019). Nuclear expression of MAGE‐A3 was also significantly related to BCR‐FS (p = 0.015). MAGE‐A3 can be considered as a predictor for poor prognosis and an option for vaccine immunotherapy in patients with PCa. [ABSTRACT FROM AUTHOR]

Melanoma has increased in incidence worldwide prompting investigators to search for new biomarkers for targeted immunotherapy of this disease. Placenta specific 1 (PLAC1) is a new member of cancer-testis antigens with widespread expression in many types of cancer. Here, we aimed to study for the first time the expression pattern of PLAC1 in skin cancer samples including cutaneous melanoma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) in comparison to normal skin and nevus tissues and potential therapeutic effect of anti-PLAC1 antibody in melanoma cancer cell lines in vitro. Polyclonal and monoclonal antibodies were applied for immunohistochemical profiling of PLAC1 expression using tissue microarray. The cytotoxic action of anti-PLAC1 antibody alone or as an antibody drug conjugate (with anti-neoplastic agent SN38) was investigated in melanoma cell lines. We observed that 100% (39 of 39) of melanoma tissues highly expressed PLAC1 with both cytoplasmic and surface expression pattern. Investigation of PLAC1 expression in BCC (n = 110) samples showed negative results. Cancer cells in SCC samples (n = 66) showed very weak staining. Normal skin tissues and nevus samples including congenital melanocytic nevus failed to express PLAC1. Anti-PLAC1-SN38 exerted a specific pattern of cytotoxicity in a dose- and time-dependent manner in melanoma cells expressing surface PLAC1. Our findings re-inforce the concept of re-expression of embryonic/placental tissue antigens in cancer and highlight the possibility of melanoma targeted therapy by employing anti-PLAC1 antibodies. The data presented here should lead to the future research on targeted immunotherapy of patients with melanoma. [ABSTRACT FROM AUTHOR]

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Tuberculosis has been declared as a global emergency. Latent tuberculosis infection (LTBI) is a state in which host immunity cannot completely eradicate Mycobacterium tuberculosis. Cigarette smoke increases the risk of respiratory infections, such a TB, as it has adverse effects on respiratory immune function. In this cross-sectional study, which was performed from 2016 to 2017, 31 patients with newly diagnosed lung cancer, 63 Chronic obstructive pulmonary disease (COPD), 46 with problems in respiratory system, and 40 healthy subjects were studied. Demographic data of all subjects were recorded via a questionnaire. IGRAs (Interferon-γ release assays) were used to determine LTBI. We showed that smoking has significant odds ratio for COPD patients (OR: 4.58, 95% CI: 1.93–10.87). Also, the concordance of smoking with COPD (OR: 22, 95% CI: 2.7–179.2), lung cancer (OR: 10, 95% CI: 1.03–97), and other respiratory diseases (OR: 4.54, 95% CI: 1.93–10.87) is a significant risk factor for the presence of LTBI whereas the existence of LTBI in the study groups did not show any significant odds ratio. This study is the first to analyze the relationship between smoking in patients with respiratory diseases and LTBI susceptibility in Iran by IGRAs, which proposes cigarette smoking as a powerful risk factor for LTBI. [ABSTRACT FROM AUTHOR]

Autism is a neurodevelopmental disorder that is recognized by stereotypic and repetitive behaviors after 2 years of old. Dysregulation of the immune system, especially inflammation which is mostly regulated by IL-6, imposes a deficit in CNS development. Along with this crucial biomarker, researchers have proposed BCL-2, micro RNA-23a-3p (miR-23a-3p), miR-181b-5p as other probable biomarkers involved in inflammation and apoptosis. The aim of the study was to evaluate the alteration in the expression of these biomarkers in a group of autism spectrum disorder (ASD) children. Peripheral blood mononuclear cells (PBMCs) were obtained from 37 autistic patients. After RNA extraction with precipitation method, the Syber green qReal-time Polymerase Chain Reaction (PCR) was performed in order to evaluate the possible alteration in the expression of IL-6, BCL-2, miR-181b-5p, and miR-23a-3p. The results were compared with healthy controls. IL-6 was significantly upregulated in ASD patients (p=0.003). On the other hand, miR-23a was upregulated and BCL-2 downregulated in ASD patients but the changes were not significant. In initial evaluations, expression changes of miR-181b-5p were not statistically significant. However, when Patients were divided into two groups of upregulated and downregulated, re-evaluation showed that both up- (p=0.005) and down-regulation (p=0.004) (i.e. changes regardless of the direction) of miR-181b were significant in autistic children. IL-6 and miR-181b-5p can have proper diagnostic values and are reliable biomarkers with high sensitivity and specificity. On the other hand, PBMC can be utilized for such studies and also evaluation of patients' condition instead of brain tissue as it is less accessible. [ABSTRACT FROM AUTHOR]

Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients. [ABSTRACT FROM AUTHOR]

Aim: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). There is a great interest in using microRNAs (miRNAs) as diagnostic and prognostic biomarkers in autoimmune diseases. Materials and methods: This study evaluated miR‐16, miR‐21, miR‐141, miR‐146a, and miR‐155 expression levels in peripheral blood mononuclear cells (PBMCs) of 55 female SLE patients with absent, inactive, or active nephritis, and 30 healthy controls (HCs) using quantitative polymerase chain reaction. Results: MiR‐21 and miR‐155 levels were significantly greater in the active nephritis group than in the absent, inactive or HC groups. Moreover, receiver operating characteristic and logistic regression analyses revealed miR‐21 and miR‐155 were significant risk factors for LN. Conclusion: Overexpression of miR‐21 and miR‐155 in PBMCs may participate in LN pathophysiology and these miRNAs could be used as biomarkers for the condition. [ABSTRACT FROM AUTHOR]

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon-gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months'(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood. [ABSTRACT FROM AUTHOR]

Background: It was proposed that probiotics may influence immune system through direct or indirect exposure. Direct exposure is mostly mediated by surface receptors. Toll-like receptors (TLRs) are conserved molecular sensors which could be triggered via some pathogen associated structures, hence, modulate the immune responses. This study was conducted to elucidate the impact of lactobacillus acidophilus as a common probiotic on the expression level of TLRs in the chicken's cecal tonsil. Methods: Thirty one-day-old chicken were selected and separated into three groups as probiotic-fed, dairy-fed and control. In addition to commercial powder supply, each chicken in the probiotic-fed group received 109 CFU/Kg of L. acidophilus daily. While, chickens in the dairy-fed group were provided with commercial powder feed and sterile dairy milk. After 14 and 21 days of oral feeding the cecal tonsil was removed and the expression of TLR2, TLR4 and TLR5 were examined by real-time PCR. Results: At the age of 14-day, there was a slight upregulation in the expression levels of TLR2 (118.9%), TLR4 (129.6%) and TLR5 (123.7%) of the cecal tonsil in the probiotic-fed group; however, these alterations were not statistically significant. At the age of 21-day, a non-significant downregulation was observed in TLR expression level of both dairy-fed (TLR2, 85%; TLR4, 79.5%; and TLR5, 86.5%) and probiotic-fed (TLR2, 88.8%; TLR4, 81%; and TLR5, 87.2%) groups in comparison to controls. Conclusions: The findings revealed that although the probiotic supplementation could be useful but it did not significantly affect innate immunity state through alteration of TLRs. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the role of allergic-type and infectious-type cytokines in children with chronic otitis media with effusion (OME) Materials and Methods: We investigated serum levels of interleukins (IL)-4, IL-5, and IL-13, along with interferon-gamma (IFN-ʏ) and tumor necrosis factor-alpha (TNF-ɑ), by enzyme-linked immunosorbent assay (ELISA) in 35 children with OME and 28 healthy controls. Results: Children with OME had significantly higher levels of IL-5 in comparison with the control group, ranging from 1 pg/ml in cases to 0.04 pg/ml in controls (P=0.009). However, after adjusting for confounding variables, there was no significant difference in serum levels of IL-13, IL-4, IFN-ʏ, or TNF-ɑ between the two groups (P=0.287, P=0.627, P=0.793, and P=0.217, respectively) Conclusions: The findings of this study suggest that in comparison with the control group, serum IL-5 levels were elevated in OME cases. [ABSTRACT FROM AUTHOR]

The pathogenesis of nasal polyps has been debated for many years. The lymphocytes that infiltrate nasal polyps have been identified as predominantly memory T cells in an activated state, and these cells produce a mixed cytokine pattern of T1 helper (Thl) and T2 helper (Th2) cells. We conducted a prospective study to compare the expression levels of some Thl and Th2 cytokines in atopic and nonatopic patients. Our study population consisted of 75 adults--42 men and 33 women (mean age: 38 yr)--with nasal polyposis. Patients with an allergy were distinguished from those without an allergy on the basis of the history, the results of skin-prick testing, and measurement of total IgE serum concentrations. Based on these criteria, patients were divided into two groups: atopic (n = 38) and nonatopic (n = 37). Levels of cytokine gene expression in the atopic patients were compared with those of the nonatopic patients by real-time polymerase chain reaction. Statistical analysis found no significant differences in the rate of interleukin (IL) 10 and IL-12 gene expression between the allergic and nonallergic patients. On the other hand, rates of interferon gamma and IL-4 gene expression were significantly higher in the atopic patients (p = 0.03 and p = 0.02, respectively). Our research suggests that an imbalance of Thl and Th2 cells plays an important role in the pathophysiology of nasal polyps. Although nasal polyposis is a multifactorial disease associated with several different etiologic factors, chronic persistent inflammation is undoubtedly a major factor, regardless of the specific etiology. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is one of the leading causes of cancer deaths among men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed only in normal prostate and prostate cancer tissue. Because of its selective expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic target. To target the NGEP in prostate cancer, it is essential to investigate its expression in prostate cancer cells. Methods: In the present study, we investigated NGEP expression in LNCaP and DU145 cells by real time and RT-PCR, flow cytometric and immunocytochemical analyses. Results: Real time and RT-PCR analyses of NGEP expression showed that NGEP was expressed in the LNCaP cells but not in DU145 cells. The detection of NGEP protein by flow cytometric and immunocytochemistry analyses indicated that NGEP protein was weakly expressed only in LNCaP cell membrane. Conclusion: Our results demonstrate that LNCaP cell line is more suitable than DU145 for NGEP expression studies; however, its low-level expression is a limiting issue. NGEP expression may be increased by androgen supplementation of LNCaP cell culture medium. [ABSTRACT FROM AUTHOR]

Background: Nasal polyp (NP) is a benign mucosal mass located in both sinuses and nares which is mostly seen in association with cystic fibrosis, asthma or oversensitivity to aspirin. The prominent histological feature of NP is inflammatory cell infiltration with eosinophil predominance. Superantigens role in causing NP complications is already proven. Superantigens, which are mostly originated from Streptococci and Staphylococci, activate T cells strongly and increase the process of production and release of cytokines, and secretion of IgE from B cells, which in turn directly affects proinflammatory cells such as eosinophils, both in their tissues infiltration and functions. Methods: The samples are collected from patients referring to ENT clinic in Rasoul Akram training Hospital in Tehran after thorough clinical and paraclinical examinations. For control group the samples collected from patients undergoing rhinoplasty. All the samples kept frozen and sent to immunology lab. The DNA of the excised tissues extracted and amplified by using the superantigens specific primers and PCR product detected by gel electrophoresis. The date analyzed by using mean and SD and X2 analytical tools. Results: Fifteen healthy individuals, 25 patients with rhinosinusitis and 24 with polyposis entered this trial. Group A Streptococcus toxin detection was significantly more frequent in those with nasal polyp and rhinosinusitis compared to healthy individuals (P=0.001 and 0.005, respectively), but the results were almost the same for those with nasal polyp and rhinosinusitis (P=0.4). Conclusion: Streptococci may play an important role in induction or clinical exacerbation of polyposis and group A Streptococcus pyogenes exotoxin (SPEs) with superantigenic effects may have a crucial role in etiology and pathogenesis of polyps with or without rhinosinusitis. It is postulated that, T cells polyclonal activation by SPEs may cause recruitment of inflammatory cells in nasal mucosa. These inflammatory cells include IgE producing B cells laeding to allergic and inflammatory reactions in NP. [ABSTRACT FROM AUTHOR]

Background: Tonsils and adenoid hypertrophy is a major respiratory symptom in children which is partly due to recruitment of inflammatory cells in upper airway lymph nodes as a result of the effects of synthesis and release of different inflammatory cytokines. It seems that infections play role in concert with these cytokines leading to tonsilar hypertrophy and other pathologic consequences. It is proposed that cellular infiltrate of tonsils and adenoids may secrete different quantities of these cytokines compared with peripheral blood mononuclear cells (PBMC) cultures. Methods: Among patients who were admitted for adenotonsillectomy to the ENT ward, 37 patients, under 1-12 years old patients with fulfill criteria selected to include the study. Excised adenoid and tonsils cultured and inflammatory cytokines Interferon-γ (INF-γ), Interlukine-1 (IL-1), IL-6, IL-8 and tumor necrosis factor-α (TNF-α) measured in cellular culture supernatant. The same cytokines measured in PBMC cultures. Results: The data shows that there is a significant difference between IFN-γ and IL-8 amounts in adenoid tissue culture supernatant and PBMC culture of our patients. Furthermore, the amounts of IFN-γ, IL-1 and IL-8 showed considerable difference between tonsilar tissue culture supernatant and PBMC culture of these patients. Although there is a significant correlation between IL-6 amounts in tissue culture supernatant and PBMC culture (P=0.02), the respective data for TNF is only almost significant. Conclusion: Inflammatory cytokines may have significant role in the early provoke of inflammation occurred in hypertrophied tonsils and adenoid. The majority of these cytokines increase the expression of adhesion molecules on epithelial cells and influence the recruitment of leucocytes and inflamed tonsils. On the other hand lack of sufficient cytokine release may lead to persistent infections and may cause chronic inflammation and hypertrophied tissue. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus secretes numerous superantigenes which trigger the inflammatory mechanisms of sinus mucosa and cause chronic rhino-sinusitis. This study was designed to evaluate the role of staphylococcus aureus superantigens in polyp tissues of patients with chronic rhino-sinusitis in comparison with a control group. Methods: Polyp tissue samples of 28 patients and mucosal specimens of 19 healthy individuals were evaluated for staphylococcus aureus bacterium superantigens, exotoxins A, B, C and D and TSST-1 with RT-PCR and ELISA methods Rasoul Akram Hospital during 2 years. Results: Polymerase chain reaction (PCR) results revealed that 88.2% of the patients and 45.5% of the controls had at least one type of superantigen (P=0.03). Evaluation of superantigens using ELISA method showed presence of at least one type of superantigen in the nasal samples of all patients and in 35.3% of the controls (P<0.001). Conclusion: A relationship between staphylococcal superantigens and nasal polyps is concluded from this study which indicates the probable role of these superantigens in the pathogenesis of nasal polyposis. [ABSTRACT FROM AUTHOR]

Background: Too many studies are in the process of determining the probable role of immune system in the etiopathogenesis of nasal polyposis. This study was designed to identify the probable participation of Th1, Th2 lymphocytes in the induction and progression of nasal polyposis. Methods: Seventy-five patients, 42 male and 33 female, with nasal polyposis were examined for total serum IgE, specific serum IgE and reaction to skin test for differentiating allergic from non-allergic participants in Rasoul Akram Hospital during 2010. To determine the possible correlation of allergic reactions in the upper respiratory tract and nasal polyposis, cytokine gene expression was evaluated on the extracted RNA by RT-PCR. The data were analyzed by using χ2, independent t-test, correlation and Receiver operating characteristic (ROC) curve. Results: The mean age of participants was 38 years (18-81 years). IFN-γ and IL-4 gene expressions were more prevalent in allergic than non-allergic individuals (IFN-γ: 39.5% vs. 14.2%, P=0.3 and IL-4: 44.7% vs. 18.9%, P=0.02, respectively). IL-10 and IL-12 (P35 and P40 fractions) genes were not significantly different between the two groups. IL-10 and IL-12 (P35, P40) genes did not differ significantly either. Conclusion: This research suggests that overproduction of cytokines and an imbalance of Th1 and Th2 cell production may play an important role in the pathophysiology of allergic or non-allergic nasal polyp formation. Thus, although nasal polyposis is a multifactorial disease with several different etiological factors, chronic persistent inflammation is undoubtedly a major factor irrespective of the etiology. [ABSTRACT FROM AUTHOR]

Background: M. pneumoniae infection in children is usual and diagnosis of its neurologic complications for rapid treatment is very important. To compare the CSFM. pneumoniae antibody level between febrile children with acute neurologic signs (Menigoencephalitis, Guillan Barre Syndrome (GBS), Transverse myelitis, Ataxia and so on) with unaffected ones. Methods: A cross sectional/ case control study in pediatric wards of Rasoul-e-Akram & Mofid hospitals (2007-2009) was done. The amount of Specific M. pneumoniae IgG (ELISA) antibody level determined in CSF of 55 cases and in 10 controls. Chi square values (CI 95%, p< 0.05) calculated for all categorical variables. Sensitivity; specificity; Positive Predictive Value (PPV); Negative Predictive Value (NPV) of CSF antibody level determined by using the Area under the ROC Curve. Results: Cases (n= 55) aged between five month to 13 years with mean age of 3.84±3.43 years. Area Under Curve (AUC) in ROC was 0.876 (%95 CI, 0.78- 0.96; p< 0.0001). Cut off level for antibody was 0.0025 with 73% sensitivity; 90% specificity; 100% PPV; 28.8% NPV. CSF antibody level had significant difference between cases and controls [0.08± 0.26 Versus 0.001± 0.001; p: 0.02]; It had poor agreement between cases and controls (Kappa= 0.27). Lowest amount seen in cases with aseptic meningitis; highest amount observed in cases with GBS and cases with focal neurologic signs. Conclusion: The presence of very low amount (0.0025) of M. pneumoniae antibody in CSF of febrile children with acute neurologic signs had 70% sensitivity and 90% specificity; 100% PPV; but had low (28.8%) NPV. M. pneumoniae would be a rare cause in cases with aseptic meningitis. Finding the M. pneumoniae-DNAs in CSF are not so frequent (2%) but in high suspicious cases adding this test to determining the CSF antibody level might be helpful. [ABSTRACT FROM AUTHOR]

Background: Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4+ and CD8+ T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells. Methods: In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4+, CD8+, and CD68+ cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10% of total inflammatory cells. The Kruskal–Wallis, Mann–Whitney, and Spearman tests were used in statistical analyses. Results: The median (range) age of the studied groups was: 32 (14–67) for CRSwNP, 28 (10–43) for CRSsNP, and 27 (17–44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neutrophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4+ and CD8+ T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls. Conclusion: The frequency of CD4+ and CD8+ T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed. [ABSTRACT FROM AUTHOR]

Presents an abstract of the article "Amniotic Fluid Alpha Feto Protein Levels in Down Syndrome Pregnancies and Other Chromosomal Abnormalities," by Ahmad Rajaee, Ariana Kariminejad, Maryam Mirzazadeh, Hanieh Jafarieh, Valeh Hadavi, Mehdi Shekarabi, Mohammad Hasan Kariminejad, Hossein Najmabadi, Raymond Dalgleish.

IgE-mediated hypersensitivity reaction to pollens is a common health problem in atopic patients. In this regard, the assessment of the allergenicity of highly pollinating plants would be demanding. Based on the increment of Ailanthus altissima (A. altissima) tree in some parts of Iran and considering its probable role in respiratory allergy, in this study, we aimed to investigate its IgE-immunoreactivity and in diagnostic applications. One hundred and twenty-five allergic rhinitis patients who were diagnosed as high IgE responders and demonstrated seasonal rhinitis or rhinoconjunctivitis, as well as 20 healthy controls (HCs) with no allergic symptoms, were enrolled in this study. Total protein extract was prepared from A. altissima pollens and subjected to quality control experiments and finally used in ELISA and western blotting studies. Approximately 24% of the atopic patients (30 from 125) showed positive immunoreactivity to A. altissima extract. The median (IQR) of absorbance (450 nm) of the specific IgE against A. altissima pollen extract in HCs and positive groups were 0.33 (0.28-0.42) and 0.59 (0.36-0.79), respectively (p<0.001). Receiver operating characteristics (ROC) curve analysis of the specific ELISA results, revealed a cut-off value of 0.46 and a sensitivity of 70% and specificity of 100%. Western blotting with the sera positive cases revealed that the main immunoreactive proteins range from 10 to 70 kDa. This study revealed that some of A. altissima pollen proteins ranging from 10 to 70 kDa show IgE-reactivity in atopic patients and may play a role in their allergic reaction symptoms.

Background: Epidemiological evidence suggests a role of Epstein-Barr virus (EBV) in triggering the pathogenesis of Multiple Sclerosis (MS). The aim of this study was to assess the EBV-specific antibodies in MS patients with various clinical patterns and their association with the production of IFN-γ, IL-12, and IL-4 cytokines compared with healthy individuals. Methods: We measured EBNA-1 IgG, VCA IgG, and production of IFN-γ, IL-12 and IL-4 cytokines in patients with different clinical patterns and healthy controls using ELISA method. Results: There was a higher titer of anti-EBV antibodies in MS patients compared to healthy controls. SPMS patients generated higher EBNA-1 levels than those with RRMS and PPMS patients whereas; the level of VCA IgG was higher in the RRMS patients than PPMS. In PPMS patients, a significant increase was found in IFN-γ and IL-12 cytokines compared to other subtypes, whereas IL-4 cytokine had a decreased level compared to RRMS patients. Higher anti-EBV antibodies are associated with increased IL-12 cytokine in RRMS patients. However, no significant correlation was found between these antibodies and other secreted cytokines. Conclusion: EBV infection is one of the strong risk factors for MS. Acting on these factors could be useful to decrease the incidence and disease exacerbation of MS. Study of the antibody levels to EBV virus could be useful for evaluating MS risk score in each clinical subtypes.

Background: Both genetic and environmental factors are important in pathogenesis of diabetes. Non HLA (Human Leukocyte Antigen) genes such as INS-VNTR and CTLA-4 in addition of HLA genes have influence on genetic susceptibility for diabetes mellitus. In this study the association of +49 A/G CTLA-4 and -23 A/T INS-VNTR polymorphisms with diabetes and their association with islet autoantibodies were investigated. Methods: Thirty four autoantibody positive adult persons with diabetes mellitus and 39 persons with Type 1diabetes mellitus (T1DM), 40 autoantibody negative Type 2 diabetes mellitus (T2DM) patients and 40 healthy controls were studied using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Results: The frequencies of -23 A/T INS-VNTR genotypes were not significantly different among study groups. It was shown that the distribution of the +49A/G CTLA-4 allele and genotype frequencies did not differ between T1DM patients, autoantibody positive adult patients and controls. With increasing CTLA-4 G allele and GG/AG genotypes, the frequency of Glutamic Acid Decarboxylase Autoantibody (GADA), Islet Cell Autoantibody (ICA) and Islet Antigen 2 Antibody (IA2A) positive patients were increased. Conclusion: Our results suggest that susceptibility allele A of -23A/T INS-VNTR does not have any role in the pathogenesis of diabetes in our patients and susceptibility allele G of +49 A/G CTLA-4 if not, has a small role in pathogenesis of diabetes in T1DM and autoantibody positive adult patients and in spite of significant increase in autoantibody negative T2DM group it does not have any role in disease pathogenesis.

The pathogenesis of nasal polyps has been debated for many years. The lymphocytes that infiltrate nasal polyps have been identified as predominantly memory T cells in an activated state, and these cells produce a mixed cytokine pattern of T1 helper (Th1) and T2 helper (Th2) cells. We conducted a prospective study to compare the expression levels of some Th1 and Th2 cytokines in atopic and nonatopic patients. Our study population consisted of 75 adults-42 men and 33 women (mean age: 38 yr)-with nasal polyposis. Patients with an allergy were distinguished from those without an allergy on the basis of the history, the results of skin-prick testing, and measurement of total IgE serum concentrations. Based on these criteria, patients were divided into two groups: atopic (n = 38) and nonatopic (n = 37). Levels of cytokine gene expression in the atopic patients were compared with those of the nonatopic patients by real-time polymerase chain reaction. Statistical analysis found no significant differences in the rate of interleukin (IL) 10 and IL-12 gene expression between the allergic and nonallergic patients. On the other hand, rates of interferon gamma and IL-4 gene expression were significantly higher in the atopic patients (p = 0.03 and p = 0.02, respectively). Our research suggests that an imbalance of Th1 and Th2 cells plays an important role in the pathophysiology of nasal polyps. Although nasal polyposis is a multifactorial disease associated with several different etiologic factors, chronic persistent inflammation is undoubtedly a major factor, regardless of the specific etiology.