Iranian Journal of Allergy, Asthma and Immunology
Volume:10 Issue: 2, Jun 2011

IgE-mediated cell signaling, induced by cross-linking of high affinity receptor for IgE (FcεRI) in the presence of antigen (Ag), is a well known mechanism described for mast cell activation in allergy and hypersensitivity reactions, which induces a spectrum of cellular responses such as secretion and up-regulation of cell surface FcεRI. Although for several years IgE binding to FcεRI was considered to be a passive sensitization process, the outcomes of several recent studies have revealed a variety of different cellular responses to IgE binding compared to IgE plus Antigen binding. The present study applied a functional proteomics-based approach to investigate mast cell signaling events and provided new insights to FcεRI-mediated cell signaling in RBL-2H3.1 cells, and may point to the activation of alternative signaling pathways in response to IgE or IgE plus Ag. Comparative analysis by 2-D PAGE of RBL cells activated with IgE plus Ag for three and four hours compared to non-activated cells was followed by mass spectrometric protein identification and provided evidence for the induction of Stathmin 1 (STMN1) gene expression in response to IgE plus Ag activation.Complementary SDS-PAGE analysis showed a distinct up-regulation of STMN1 induction in response to challenge with IgE plus Ag compared to sensitization with IgE only. Phosphoproteomics analysis gave evidence for significant increase at phosphorylation of STMN1 on ser16 after 1min, though a slight rise at 5 min, and on ser38 after 1 and 5min sensitization with IgE and a similar result was observed for 1min IgE plus Ag-activation. IgE plus Ag-activation was also found to induce the phosphorylation of ser38 to a greater extent than sensitization with IgE. In contrast, IgE alone was more effective than IgE plus Ag at inducing phosphorylation of ser16. Collectively this study provides further insights into the role of stathmin 1 in FceRI-mediated activation of cells of mast cell lineage and might shed light on the diverse response of these cells to IgE or IgE plus Ag.

Vitiligo is a pigmentation disorder in which inflammatory mediators such as cytokines have a pivotal role in disease's pathogenesis. Interleukin 17 (IL-17A) is a proinflammatory cytokine which is involved in the induction of several proinflamatory mediators such as cyclooxygenase 2 (COX2). The aim of this study was to investigate the gene expression of IL-17 and COX2 in peripheral blood leukocytes of vitiligo's patients.Peripheral blood leukocytes from 15 patients with vitiligo and 15 healthy controls were separated using a gradient density centrifugation method. After total RNA isolation and cDNA synthesis, IL-17 and COX2 gene expression were quantified by real-time polymerase chain reaction (PCR). There were no significant differences in IL-17 and COX2 gene expression in lymphocytes of patients with vitiligo compared with control group (p<0.05). However there was an increased IL-17 and COX2 gene expression in neutrophils of patients compared to controls, but it did not reach statistical significance (p=0.05). We could not find any differences in IL-17 and Cox2 gene expression between clinical diseases subtypes, sex and age. There was a significant correlation between IL-17 and COX2 genes expression in the neutrophils of patients (p=0.00, r=0.80). Our results showed an increased expression in IL-17 and Cox-2 genes in neurophils of patients with vitiligo. This suggested that these two factors are involved in the inflammatory process. Further studies with a larger sample size might help to establish the role of these factors in the pathogenesis of diseases.

The innate immune system recognizes the presence of bacterial products through the expression of a family of membrane receptors known as Toll-like receptors (TLRs). Polymorphisms in TLRs have been shown to be associated with increased susceptibility to diseases such as inflammatory bowel disease. The aim of this study was to determine whether there was a correlation between polymorphisms of TLR4 (Asp299Gly; Thr399Ile) and TLR2 (Arg677Trp; Arg753Gln) genes and risk of colorectal cancer. DNA from 60 colorectal carcinoma patients from 3 major races in Malaysia (22 Malays, 20 Chinese and 18 Indians) and blood from 50 apparently healthy individuals were evaluated. Control group were matched to study group by race and age. The polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Genotyping results showed two out of sixty tumor specimens (3.3%) harbored both variant TLR4 Asp299Gly and Thr399Ile alleles. In contrast, DNA isolated from blood cells of 50 apparently healthy individuals harbored wild type TLR4. In the case of TLR2 Arg753Gln genotyping, all of the fifty normal and 60 tumors were of the wild type genotype. TLR2 Arg677Trp genotyping showed a heterozygous pattern in all samples. However, this may not be a true polymorphism of the TLR2 gene as it is likely due to a variation of a duplicated (pseudogene) region. There was only a low incidence (2/60; 3.3%) of TLR4 polymorphism at the Asp299Gly and Thr399Ile alleles in colorectal cancer patients. All normal and tumor samples harbored the wild type TLR2 Arg753 allele. Our study suggests that variant TLR4 (Asp299Gly and Thr399Ile alleles) as well as TLR2 (Arg753Gln allele) are not associated with risk of colorectal cancer.

Allergic Rhinitis (AR) is one of the most common chronic diseases in the developed countries. This study was performed to investigate the effect of CpG-ODN in alteration of T-helper (Th)1/Th2 balance of patients with AR treated with intranasal corticosteroids (INCs) and antihistamines. Peripheral blood mononuclear cells (PBMCs) of 20 patients with AR were isolated before and after 45 days therapy. Cytokine production (IL-4, IL-10, IL-13, IFN-γ) and specific Ch.a IgE in response to CpG co-administration of natural chenopodium album (CpG/Ch.a) or recombinant Ch.a (CpG/rCh.a) allergen were investigated in supernatants.of cultured PBMCs using ELISA Intracellular IL-10 was also assessed in CD4+ cells using flow cytometry. Significant increase in production of IFN-γ and IL-10 and decrease in production of IL-4 were found in supernatants of cultured PBMCs activated with CPG/ch.a and CPG/rch.a. of both CpG/Ch.a and CpG/rCh.a compared to allergens alone, before and after therapy. After therapy, IFN-γ production with CpG/Ch.a was significantly increased in comparison with before (237 vs. 44 pg/ml, p=0.001). IFN-γ and IL-10 production with CpG/rCh.a was significantly increased after therapy compared to before (407.6 vs. 109 pg/ml, p=0.01 for IFN-γ; 171.7 vs. 52.6 pg/ml, p=0.008 for IL-10), whilst IL-4 was significantly decreased (2.1 vs. 5.8 pg/ml, p=0.02). Intracellular IL-10 expression was also significantly increased in response to either CpG/Ch.a or CpG/rCh.a that showed intracellular assay could be more sensitive than ELISA. Also, treatment with intranasal corticosteroids and antihistamines could enhance this CpG effect, in vitro.

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologous serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.

Both genetic and environmental factors seem to play role in the etiology of Meniere's disease (MD). Several genes may be involved in susceptibility of MD including Human Leukocyte Antigens (HLA). The associations between MD and HLA alleles have been previously studied in other populations and certain HLA alleles were shown to be predisposing. The aim of this study was to determine the association between HLA-C allele frequencies and definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center in Tehran. Patients with definite MD (N=22) enrolled according to the diagnostic criteria of American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Cases with all 3 symptoms of MD (Vertigo, Tinnitus and lower frequency of sensory-neural hearing loss) were included and those with suspected MD were excluded from study. HLA-Cw allele frequencies were determined in patients non-related healthy controls (N=91) using PCR -SSP. We found that the frequency of HLACw*04 was significantly higher in patients compared to the controls [P = 0.0015, OR; 20, 95% CI (3.7-196.9)]. Our results revealed that HLA-C is a genetic predisposing factor in definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center.

Allergic diseases are frequent in children and their prevalence and severity differ in the different regions of the world. The association between pet ownership in childhood and subsequent asthma and sensitization is very controversial.In our survey conducted with standardized method (International Study of Asthma and Allergies in Childhood), 3200 children 6-7 years old were questioned regarding asthma, allergic rhinitis and eczema.The prevalence of Attacks and shortness of breath with wheezing during last 12 months in the children who had exposure to pets in the first year of life was 34.3% 'that was less than children who had not exposure (OR=3.06, 95% confidence interval [CI] 1.14-8.21, P=0.021). Also during the past 12 months the prevalence of night dry coughs, allergic rhinitis symptoms and eczema symptoms in those who had pet exposure in the first year of their life was lower than the children did not have it. However there was no significant difference in some other symptoms of asthma in two groups.Our findings suggest that pet exposure in the first year of life can have a protective effect on asthma, allergic rhinitis and eczema.

SCID disorder is major failure of the immune system, usually genetic. The aim of this study was on mutations detection of RAG1, RAG2, and IL7RG genes in SCID cases. Mutation detection was performed by PCR sequencing. Our results indicated that 13 mutations were found through cases which include 4 mutations in IL7R gene (T661I, I138V, T56A, C57W), 7 mutations in RAG1 (W896X, W204R, M324V, T731I, M1006V, K820R, and R249H), and 2 mutations in RAG2 gene (R229W, ΔT251).

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency disease, predisposing the patients to various tissue involvement and organ damage. Here a 16-year-old boy is presented who was referred to our center with cough, dyspnea, cyanosis, and history of recurrent pneumonia. The diagnosis of CVID was made according to reduction all serum immunoglobulin levels, normal numbers of T, B and NK lymphocyte subpopulations, poor antibodies responses. Considering abnormality in heart examination and chest X-ray, echocardiography and computed tomography angiography were performed which showed large thoraco-abdominal aortic aneurysm in this patient. Although there are some reports of cardiovascular disease associated with primary antibody deficiencies, this is the first time that such large thoraco-abdominal aortic aneurysm is reported in CVID. This may be secondary to recurrent pulmonary infections or an unknown mutation process. Cardiovascular abnormalities are an entity that should be kept in mind in patients with primary immunodeficiency diseases.

Flavonoids polyphenolic compounds that exert many anti-inflammatory and anti-microbial effects, and exhibit an anti-allergic action. Quercetin is a flavonoids that recently has raised many issues and shown evidence about its action as a potential drug to allergy. A Chinese herbal formula, known as Food Allergy Herbal Formula (FAHF) has been related with blocking of anaphylaxis to peanuts (PNA) in mouse models. Quercetin appears to possess the same potential of FAHF as a safe anti-allergic substance but it opens only a wide perspective, at the moment, due to several complex issues that hamper the possibility to use natural medicine and phytochemicals as true drugs.