Iranian Journal of Allergy, Asthma and Immunology
Volume:14 Issue: 2, Apr 2015

MicroRNAs participate in the regulation of asthma, the goal of this study is to summarize recent researches on the roles of microRNAs in the pathogenesis of asthma.A review of the English medical literatures was conducted by searching PubMed for studies concerning asthma and microRNAs.The results of the present study indicate that microRNAs play important roles in regulating asthma immune responses. MicroRNAs not only participate in determining DCs phenotype and then naive T lymphocyte differentiation, but also participate in the regulation of airway inflammation and airway remodeling in asthma. Furthermore, microRNAs are also shown to be targets for asthma therapy in the future.

Hyperimmunoglobulin E Syndrome (HIES) is a complex primary immunodeficiency characterized by both immunologic and non-immunologic manifestations. High serum IgE level, eosinophilia, eczema, recurrent skin and lung infections constitute the immunologic profile of HIES, whereas characteristic facial appearance, scoliosis, retained primary teeth, joint hyperextensibility, bone fractures following minimal trauma and craniosynostosis are the main non-immunologic manifestations. The diagnosis of HIES cannot be made by routine immunologic tests. As the main characteristic laboratory abnormalities of this syndrome are highly elevated serum IgE levels and eosinophilia; both features have a broad spectrum of differential diagnosis. The purpose of this essay was presenting the best way for diagnosis management of HIES. Based on the genetic reports of patients of the Center for Chronic Immunodeficiency (CCI) as a single center experience, and applying project management (PM) in health care research projects, we sought the best way for a rapid diagnosis of HIES. The combination of project management principles with immunologic and genetic knowledge to better define the laboratory and clinical diagnosis lead to an improvement of the management of patients with HIES. These results are shown in one «Decision Tree» which is based on 342 genetic reports of the CCI during the past ten years. It is necessary to facilitate the diagnostic analysis of suspected HIES patients; applying project management in health care research projects provides a better and more accurate diagnosis eventually leading to a better patients’ care. This Abstract was presented at 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), Prague, Czech Republic.

Aeroallergens continue to have a key role in the pathogenesis of asthma and allergic diseases and have recently received increased attention in medical research throughout the world. The prevalence of aeroallergens vary in different regions, depending on the type of climate. The aim of the present study was to determine prevalence of the sensitivity to aeroallergens among patients with asthma and allergic rhinitis (AR), based on skin prick test (SPT) reactivity in the province of Bushehr, Iran.In this cross-sectional study, 743 patients were enrolled. The participants had asthma and AR and reacted to at least one allergen with SPT. Skin prick test with standard extracts including house dust mites (HDMs), animal dander, molds and pollens were performed on patients according to the herbal geography of the area.The male to female ratio and mean age of the patients were 1.03 and 27.6± 15.4 year, respectively. Out of 567 patients with AR, the common aeroallergens were HDMs (88.5%), molds (82.9%), animal dander (79.5%), weeds (77.6%), trees (75.5%) and grass pollen (71.5%). Moreover, among 176 patients with asthma, the prevalence of aeroallergens were HDMs (90.5 %), molds (80.7%), animal dander (77.5%), weeds (73.3%), trees (73.3%) and grass pollen (67.9%). The sensitivity to animal dander, Chenopodium album and Russian thistle pollens were significantly associated with the severity of AR. Moreover, sensitivity to animal dander such as cat and feather of birds, cockroach, Bermuda grass and Chenopodium album pollens were significantly associated with the severity of asthma.The results of this study revealed that HDM was the most common sensitizing aeroallergen in patients with asthma and AR. Molds and animal dander as indoor allergens were also common aeroallergens. We suggest that the hot weather and ambient humidity in the region may be the main cause of the change in the pattern of SPT reactivity.

Platanus acerifolia, London plane tree, a significant source of airborne allergens, is widely grown in Shanghai and other cities in China. In recent decades, little has been known regarding the influence of the allergens on sensitizing the population in the Shanghai area. The aims of this study were to purify and characterize the two major allergens and to confirm the immunological activities of these pollen allergens in Shanghai.Crude extract was purified with a HiTrap SP column and a Sephedex G75 column. Immunodetection was performed with ELISA and immunoblotting. Following gel proteolytic digestion and mass spectrometry, the tandem MS (MS/MS) peptide mass fingerprint was obtained and the MASCOT search engine was used to identify the peptide. The accession number of the interesting homologous data and all the sequence information was acquired by an internet database and the evolutionary trees were drawn with Mega 4.0 software.Two proteins with molecular weights of 43 kDa and 18 kDa were purified from P. acerifolia pollen extract. The purified proteins were identified as pollen allergen Pla a 1 and Pla a 2 via mass spectrometry. The proteins have immunological activities with human IgE antibodies. According to the ELISA results, 12% (5/41) of the subjects were sensitive to Pla a 1 and 9% (4/41) were sensitive to Pla a 2.Pla a 1 and Pla a 2 are thus important allergens for patients with an allergic reaction to P. acerifolia pollen in Shanghai.

Brain death is associated with increased inflammatory cytokines levels and poor graft quality to transplant. We aimed to evaluate the impact of Ascorbic Acid (AA) on the inflammatory status of Brain-Dead Donors (BDDs).Forty BDDs were randomly divided into two groups. Donor treatment (n=20) consisted of 100 mg/kg AA infusion 6 hours before donor operation and subsequent infusion of 100 mg/kg/p6h until organ removal. Blood samples were taken at three times, 6 hours before donor surgery (TP1), immediately after laparotomy (TP2), and before organ removal (TP3). Gene expression level and serum concentration of IL-6 and TNF-α cytokines were assessed by real-time PCR and ELISA methods. To investigate transplanted liver function, serum values of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Billirubin-Total were evaluated on the 1st, 3rd, and 10th postoperative days.We found a significant reduction in IL-6 mRNA expression ratio of TP3 to TP1 following AA application among BDDs. Despite the considerable decrease in treated donors regarding IL-6 mRNA expression ratio of TP2 to TP1, TP3 to TP2, and also TNF-α variations in these periods, the results were not significant. Regarding serum concentration of these cytokines, particularly IL-6, there was a decrease between TP2 and TP3 following AA application in the treated donors. Furthermore, a significant reduction was found in serum AST and ALT levels in the recipients of treated group on the 3rd day compared to the 1st day after transplantation.It seems that AA beneficially affects the inflammatory status of BDDs, resulting in improved primary allograft function.

Cytokines have been introduced as critical inducers in the development of Th subpopulations.Cytokines like IL-10 are involved in inducing regulatory T cells such as Type 1 regulatory T (Tr1) cells cells. IL-22 is a member of IL-10 family of cytokines, and IL-28A is a member of IFN-γ family.In this study, cord blood mononuclear cells (CBMC) from normal healthy individuals were isolated by Ficoll and then naïve T cells were purified by CD4+CD25+ Regulatory T cell Isolation kit. The effect of these two cytokines on production of IL-5, TGF-β, IL-10, IL-4 and IFN-γ cytokines from cord blood T cells was investigated to identify Tr1 cells as well as Th1 and Th2 polarization.Flow cytometric analysis showed that IL-28A and IL-22 were not effective in expression of IL-5 and TGF-β either alone or in synergy, but in view of IL-10, IL-4 and IFN-γ, the results showed that IL-22 increased IL-10 and IL-4 but had a decreasing effect on IFN-γ. The results showed that IL-28A was not effective in increasing or decreasing the level of IL-10, IL-4 and IFN-γ.Therefore, according to these results, IL-22 and IL-28A were not effective in inducing Tr1 cells.

Computational tools are reliable alternatives to laborious work in chimeric protein design. In this study, a chimeric antigen was designed using computational techniques for simultaneous detection of anti-HTLV-I and anti-HBV in infected sera.Databases were searched for amino acid sequences of HBV/HLV-I diagnostic antigens. The immunodominant fragments were selected based on propensity scales. The diagnostic antigen was designed using these fragments. Secondary and tertiary structures were predicted and the B-cell epitopes were mapped on the surface of built model. The synthetic DNA coding antigen was sub-cloned into pGS21a expression vector.SDS-PAGE analysis showed that glutathione fused antigen was highly expressed in E. coli BL21 (DE3) cells. The recombinant antigen was purified by nickel affinity chromatography. ELISA results showed that soluble antigen could specifically react with the HTLV-I and HBV infected sera.This specific antigen could be used as suitable agent for antibody-antigen based screening tests and can help clinicians in order to perform quick and precise screening of the HBV and HTLV-I infections.

The interaction between immune cells and endothelial lining of blood vessels is vital in many processes such as inflammatory and immune responses as well as cancer cell metastasis. The expression level of VCAM-1 is regulated by many factors including the promoter activity that is possibly affected by the single nucleotide polymorphisms (SNPs) present in the promoter. There are previous reports suggesting an important role for rs3783605 at -420 position in the pathogenesis of VCAM1-associated diseases. This is possibly due to the effect of this SNP on promoter activity and gene expression. Therefore, present study was designed to investigate the effect of rs3783605 on the activity of VCAM-1 gene promoter in human umbilical vein endothelial cells (HUVEC).In this study, two appropriate expression vectors containing VCAM1 promoter with different alleles of rs3783605 were constructed to express the Green Fluorescent Protein (GFP). Expression vectors were transfected into HUVECs and their EGFP expression level was assessed by the fluorescent microscopy and real-time PCR.Bright green fluorescence was seen in the HUVECs transfected by expression vector containing CMV promoter. The expression level in the cells transfected by vector containing promoter with A allele of rs3783605 was 0.14888 folds and G allele was about 0.37851 folds of cells transfected by vector having CMV promoter (p<0.001). Moreover, HUVECs transfected by G allele of rs3783605 showed about 2-fold higher transcriptional activity compared with the A allele, (p=0.049).Our findings showed that rs3783605 polymorphism may play a role in VCAM-1 gene expression. Therefore, it is likely that it may have an important role in the pathogenesis of VCAM1-associated diseases and tumor metastases.

Kawasaki disease (KD) is an acute febrile systemic vasculitis of childhood characterized by elevated levels of inflammatory mediators at the acute stage. High-dose intravenous immunoglobulin (IVIG) is well accepted as a conventional therapy for KD. The aim of the present study was to determine the expression level of Toll like receptors (TLRs) and their corresponding signaling mediators in PBMCs of IVIG-treated KD patients.TLR2, 3, 9 and signaling mediators, MyD88 and TRIF transcript levels were determined in PBMCs from 31 KD patients, before (acute phase), 2 weeks later (sub-acute phase) and 6 weeks later (convalescent phase) of IVIG therapy using real time PCR. The mean age of the patients was 3.6 years and 65% of subjects were male and 35% were female. 20 age-matched irrelevant febrile patients and 20 healthy subjects were included as control groups.Elevated levels of TLR2, MyD88, and TRIF gene transcripts were observed in the PBMCs at acute phase of untreated KD patients in compression with normal subjects. IVIG therapy resulted in significant decrease in TLR2, 3 and 9 (60-90%) as well as MyD88 and TRIF (60-70%) transcripts following 2 and 6 weeks.With Regard to significant up-regulation of MyD88 and TRIF at the acute phase of KD, our findings suggest TLR signaling pathway potential in KD pathogenesis and may also support the assumption of an infectious background in KD. Down-regulation of TLR members and corresponding mediators in IVIG treated patient suggest general TLR pathway suppression as a novel anti-inflammatory mechanism of IVIG.

Primary Sjögren’s syndrome (pSS) is a common autoimmune disease involving abnormal Th17 activation. The aim of the current study was to investigate the immunosuppression effect of Cyclosporine A (Cys A), a potent immunosuppressor on the proliferation and activation of T cells, on the activation of Th17 cells.Blood samples from both inactive and active pSS patients as well as healthy controls were collected and serum and peripheral blood mononuclear cells (PBMCs) were collected and tested for IL-17 and RORγt expression. Subsequently, PBMCs were treated in vitro with Cys A in a series of doses and incubation time and the effect of Cys A on inhibiting Th17 activation was tested by measuring IL-17 and RORγt expression.IL-17 in both serum and PBMCs as well as RORγt in PBMCs from active pSS patients were significantly elevated on both the mRNA and protein levels comparing to those from both inactive pSS patients and healthy controlCys A in the final concentration of 80ng/ml and the treatment time of 24h showed strong inhibition effect on the expression of IL-17 and RORγt in PBMCs from active pSS patients. However, Cys A in various doses and incubation times did not show much impact on inhibiting IL-17 as well as RORγt expression in PBMCs from healthy donors and inactive pSS patients.Cys A possesses the capability in immunosuppressing the activation of Th17 cells, suggesting that Cys A may be a potential treatment for pSS and maybe other autoimmune diseases.

Multiple Sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of some cytokines, expression of adhesion molecules and these cytokines may cause damage to the myelin sheath and axons.In this study, we analyzed plasma levels and gene expressions of five important cytokines in the new diagnosed MS Patients by ELISA and Real time PCR. PCR amplifications were performed to determine the IL-17, IL-23, IL-10, IL-27 and TGF-β mRNA expression levels using the SYBR Green PCR Kit.Our results showed significant decrease in IL-10, IL-27 and TGF-β but there was no significant difference in the IL-17 and IL-23 between patients and healthy controls. Altogether, our results indicated that dysregulation of cytokines, mainly increased expression of pro-inflammatory cytokines and decreased expression of inhibitory cytokines occurred in MS patients. This study may shed light to the probable role of these cytokines in neurodegeneration mechanism and current or future use of cytokines in managing and treatment of multiple sclerosis.

Human leukocyte antigen-G which is an immune tolerance effecter molecule has an important role in the maintenance of fetus during pregnancy. Abortion is one of the complications of pregnancy period. In this research, we have studied levels of HLA-G 5, HLA-G7 isoforms in the abortion-threatened pregnant women in comparison with controls.In a case-control study, 101 abortion-threatened women and 101 healthy pregnant women (healthy controls) with age range 21-32 years were studied. Gene expression of HLA-5 and HLA-7 isoforms was analyzed by real-time polymerase chain reaction after mRNA extraction and cDNA synthesis.The results indicated that HLA-G5 was significantly lower in abortion-threatened women in comparison with the control group whereas HLA-G7 was not significantly differentbetween the 2 groups.HLA-G is a vital molecule during pregnancy that can be a key factor in prevention of abortion. It is concluded that determination of HLA-G5 can be of value in pregnancy.

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria.This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done.Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score.This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

This is a letter to the editor.