Iranian Journal of Allergy, Asthma and Immunology
Volume:12 Issue: 1, Mar 2013

Asthma is one the fastest growing syndromes in many countries and is adding a huge cost to the health care system. Increasing reports have linked airway infectious diseases to asthma. Influenza is one the most serious airway infectious diseases and in recent years there havebeen some serious influenza virus pandemics which caused increased fatality in numerous different populations. Diverse host response pathways during virus infection have been identified, including different cell death and survival pathways. These pathways include 1) programmed cell death I (apoptosis), 2) programmed cell death II (autophagy), and 3) endoplasmic reticulum stress with subsequent unfolded protein (UPR) response. There has been extensive research on the regulatory roles of these pathways during the influenza virus life cycle. These studies address the benefits of enhancing or inhibiting these pathways on viral replication. Here we review the most recent and significant knowledge in this area for possible benefits to clinicians and basic scientist researchers in different areas of the respiratory and virology sciences.

Molecular evidence of the heterogeneity present in the Ole e 1 allergen of the olive pollen is arising. Such polymorphism is dependent on the cultivar origin of pollen, which also determines wide differences in the expression of this protein. Determination of biochemical and molecular characteristics of Ole e 1 pollen allergen in two Iranian olive cultivars: 'Rowghani' and 'Zard' is necessary to assess their allergenicity potential. SDS-PAGE and immunoblotting analysis of pollen extracts showed that both cultivars present high and low expression of Ole e 1, respectively. These protein levels correlated with similarly different levels of transcripts, as determined by RT-PCR. Two-dimensional protein profiles also showed conspicuous differences in the distribution and the level of expression of those spots reacting to an anti-Ole e 1 antibody. Bioinformatic analysis of four Ole e 1 sequences corresponding to 'Rowghani' and two sequences for 'Zard' showed numerous heterogeneities when compared with those Ole e 1 and Ole e 1-like sequences present in databases. Nucleotide substitutions resulted in many cases in changes over the predicted amino acid sequences. A cladistic analysis of the sequences showed Iranian entries in a central position between West- European sequences, and Ole e 1-like sequences from other Oleaceae species. Moreover, amino acid changes affected key epitopes of the protein involved in the recognition of the protein by the human immune system. Putative implications of polymorphism in both the biological role and the allergic reactivity of Ole e 1 are discussed.

Chemokines and their receptors play an important role in the late inflammatory stage of asthma. In this study, we aimed to investigate polymorphisms of MCP-1 (CCL2), CCR2 and CCR5 which can affect qualitatively and/or quantitatively their production and thus influence both susceptibility and severity of asthma and its clinical and biological features. MCP-1 (A/G -2518), CCR2 (+/64I), CCR5 (G/A -59029) and CCR5 (∆32) polymorphisms were evaluated by PCR in 107 Tunisian patients with asthma and 169 healthy controls. No significant association was found between the four investigated polymorphisms and asthma. Nevertheless the haplotype MCP1*AG/CCR2*+/+ was significantly less frequent in patients (20.5%) compared to controls (32.5%) (p=0.03; OR=0.54; 95% CI: 0.29-0.98). No difference was observed in CCR2/CCR5 haplotypes between patients and controls. Analysis of polymorphisms with clinical and biological features showed that the concomitant presence of MCP-1*G/CCR2*64I alleles was less frequent in severe forms (4.34%) compared to moderate disease (12%) but the difference was not significant (p=0.27). No association was observed between the four polymorphisms and the presence of atopic rhinitis or atopic conjunctivitis and an elevated rate of serum IgE over 200 IU/ml. Additional effects of MCP-1 and its receptor CCR2 polymorphisms seem to be involved in disease susceptibility to asthma in Tunisian patients; nevertheless they could be protective against its severe forms

The Wharton’s jelly of the umbilical cord is believed to be a source of mesenchymal stem cells (MSCs) which can be therapeutically applied in degenerative diseases. In this study, we investigated the immunomodulatory effect of umbilical cord derived-mesenchymal stem cells (UC-MSCs) and bone marrow-derived-mesenchymal stem cells (BM-MSCs) on differentiation, maturation, and endocytosis of monocyte-derived dendritic cells in a transwell culture system under laboratory conditions. Monocytes were differentiated into immature dendritic cells (iDCs) in the presence of GM-CSF and IL-4 for 6 days and then differentiated into mature dendritic cells (mDCs) in the presence of TNF-α for 2 days. In every stage of differentiation, immature and mature dendritic cells were separately co-cultured with UC-MSCs and BM-MSCs. The findings showed that UC-MSCs and BM-MSCs inhibited strongly differentiation and maturation of dendritic cells at higher dilution ratios (1:1). The BM-MSCs and UC-MSCs showed more inhibitory effect on CD1a, CD83, CD86 expression, and dendritic cell endocytic activity, respectively. On the other hand, these cells severely up-regulated CD14 marker expression. We concluded that UC-MSCs and BM-MSCs could inhibit differentiation, maturation and endocytosis in monocyte-derived DCs through the secreted factors and free of any cell-cell contacts under laboratory conditions. As DCs are believed to be the main antigen presenting cells for naïve T cells in triggering immune responses, it would be logical that their inhibitory effect on differentiation, maturation and function can decrease or modulate immune and inflammatory responses.

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients’ humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients’ serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency. Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy.

Recent studies have indicated the profound anti-tumor activity of artemisinin's compounds, among which; arteether is an oil-soluble derivative of artemisinin with an endoperoxide bridge that can induce apoptosis in tumor cells but not in the normal cells. An experiment was carried out on tumor-bearing Balb/c mice to estimate the effects of Arteether on tumor growth and antitumor immune responses. Briefly, 6mg/kg/day of Arteether and diluents were administered to two groups of mice. Tumor sizes were measured using digital verniercallipers. Mice were sacrificed and splenocytes were harvested for lymphocyte proliferation assay, the level of IL-4 and IFN-γ cytokines, and the percentage of splenic T regulatory cells were measured. According to the findings, there were no statistical differences between the groups with respect to the level of IFN-γ, IL-4 and proliferation assay; while our results showed that Arteether is effective in the reduction of tumor growth rate. In general, intra-tumoral injection of Arteether as an oil-soluble derivative of artemisinin brings to light some antitumor properties that may aid in development of more effective antitumor agents.

One of the most important goals in treating chronic diseases, especially asthma, is the promotion of quality of life (QOL). The present study aimed at identifying the effect of educating method on the QOL of children, who suffered from asthma. In this clinical trial study, 80 children aged 6-12 years with asthma were divided into two groups: control (face-to-face method) and experimental (visual concept mapping method). The QOL of both groups was measured before and after educating by the Juniper’s Quality of Life Questionnaire with a one-month interval. The rate of change in the QOL score of the experimental group was 0.3 (±0.7) both before and after intervention and 0.1 (±0.3) in the control group, which was statistically significant (p<0.05). Educating by the visual concept mapping method with regard to the manner of using sprays is taken into account as an efficient and effective method in improving the QOL of children with asthma.

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa with high morbidity and prevalence. Natural killer (NK) cells might have a role in AR. We aimed to evaluate the changes of the markers and receptors on NK cells in AR patients compared to the non-atopic controls. Flow cytometric analysis was used with double staining of the Peripheral Blood Mononuclear Cells (PBMCs) to examine the expression of CD25 and CD69 markers, and NKG2D and NKG2A receptors on NK cells of 20 patients with AR and 20 non-atopic controls. The serum total IgE level was measured by Enzyme-linked Immunosorbent Assay. The expression of CD69 antigen on NK cells in AR patients was significantly higher than that of healthy group (p=0.03). No significant changes were observed between CD25, NKG2D and NKG2A expression on the surface of NK cells from healthy and AR subjects. Our study also showed that there was no significant correlation between the expression of CD69, CD25, NKG2D and NKG2A and level of serum total IgE in AR patients and normal subjects. These results indicated that the expression of CD69 antigen on NK cells of AR patients was increased. The high expression of CD69 on NK cells in AR patients suggested that these cells were activated, probably due to the cytokines secreted from allergen-stimulated T cells and activated monocytes.

Peri-implantitis is a multi-factorial disease involving peri-implant tissues and resulting in therapeutic failure. Inflammatory mediators and cytokines in the Gingival Crevicular Fluid (GCF) have pivotal roles in the disease pathogenesis and could be used for disease monitoring. Therefore, the present study was conducted to compare the GCF levels of TNF-α and IL-17 between patients with peri-implantitis and healthy implants. In this case-control study, 24 patients with peri-implantitis and 18 individuals with healthy implants referring to faculty of dentistry in Tehran University of Medical Sciences were selected. GCF was collected by paper cons number 30. Samples were preserved in PBS -70ºC. TNF-α and IL-17 levels in GCF were determined by ELISA method. Data were analyzed by SPSS software version 13, using descriptive indices and independent t tests. Mean probing depth in peri-implantitis and control groups were 6.2 ± 1.1 and 3.7 ± 1.6 mm respectively. Mean level of IL-17 in patients with peri-implantitis was significantly more than the control group (19.8 ± 16.0 versus 9.3 ± 8.4 pg per site in 40 seconds, p=0.016). Also, mean level of TNF-α in patients with peri-implantitis was more than control group (39.0 ± 3.9 versus 14.5 ± 9.0 pg per site in 40 seconds, p =0.000). The significant higher levels of TNF-α and IL-17 in patients with peri-implantitis compared to control group indicated the pivotal role of these cytokines in peri-implantitis and could be suggested as diagnostic markers and in future possibly for immunomodulatory treatments.

Breast cancer patients are susceptible to infections such as candidiasis. Due to the importance and the role of matrix metalloproteinases (MMP) in breast cancer progression and its correlation with tumor metastasis, we analyzed the serum level of MMPs -2, -3, -9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in breast cancer bearing mice in the presence of systemic Candida albicans infection. Female BALB/c mice were divided into 4 groups: group I had tumor + candidiasis; group II, tumor only; group III, candidiasis only and group IV as negative control. Tumor tissue was separated from stock breast cancer bearing mice and transplanted subcutaneously into the groups I and II mice. Two weeks after tumor transplantation, groups I and III were infected with Candida albicans by intravenous injection. One week after systemic infection, the sera of the experimental groups were prepared and analyzed with ELISA for MMP-2, -3, -9 and TIMP-1 levels. The results showed that the levels of MMP-3, MMP-9 and TIMP-1 were increased in groups I, II and III, as compared to the control group. However, the level of MMP-2 was decreased in mice infected with Candida albicans and in infected mice bearing tumor. These data suggest that candidiasis may have a positive effect on tumor progression and metastasis.

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients. Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed. The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies. According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran.

Food Dependent Exercise-Induced Allergy is a rare condition. However, the occurrence of anaphylaxis is increasing especially in young people. The diagnosis of anaphylaxis is based on clinical criteria and can be supported by laboratory tests such as serum tryptase and positive skin test results for specific IgE to potential triggering allergens. Anaphylaxis prevention needs strict avoidance of confirmed relevant allergen. Food-exercise challenge test may be an acceptable method for diagnosis of Food Dependent Exercise-Induced Allergy and dietary elimination of food is recommended to manage it. In this study, a 32 year-old woman visited the allergy clinic with a history of several episodes of hives since 11 years ago and 3 life-threatening attacks of anaphylaxis during the previous 6 months. The onsets of majority of these attacks were due to physical activity after breakfast. On Blood RAST test, the panel of common food Allergens was used and she had positive test only to wheat flour. On skin prick tests for common food allergens she showed a 6 millimeter wheal with 14 mm flare to Wheat Extract. The rest of allergens were negative. The patient was diagnosed as wheat-dependent exercise-induced, and all foods containing wheat were omitted from her diet. In this report we emphasized on the importance of careful history taking in anaphylaxis diagnosis.