Iranian Journal of Allergy, Asthma and Immunology
Volume:13 Issue: 2, April 2014

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity.To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex-matched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and glucocorticoid induced tumor necrosis factor receptor (GITR) were also assessed by quantitative Real-time PCR TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and TGF-β were also measured.Results showed that the frequency of Tregs and the mean fluorescence intensity of FOXP3 protein significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction in relative expression of both CTLA-4 and GITR mRNA in ITP patients (P=0.02 and P=0.006, respectively). The suppressive function of Tregs also diminished in ITP patients compared to that in controls. Both IL-10 and TGF-β cytokines were produced in lower amounts in ITP patients than controls.It could be concluded that alteration in Treg frequency and functional characteristics might be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients.

Cytokine production in response to allergens may influence the development of atopy-predisposing immune responses, initializing the early programming of allergy and asthma. Vitamin D intake may be protective due to its immunoregulatory properties, that may contribute to influence the expression of the atopic phenotype initiated in early life. The objective of our study was to investigate the effects of 1,25-(OH)2D3 on allergen-stimulated expression of asthma related cytokines in cord blood T cells.Cord blood samples were collected from the umblilical vein of 24 term deliveries during labor, CD4+T cells derived from cord blood mononuclear cells (CBMCs), were cultured for 72 hours with ovalbumin (OVA), β-lactoglobulin (β-LG), respectively, in presence or absence of 1,25-(OH)2D3 to detect the levels of interleukin-13 (IL-13) and interleukin-17 (IL-17) in culture supernatants and the mRNA expressions in CD4+T cells.After allergens stimulation, CD4+T cells showed an increase of IL-13 and IL-17 production, while cultured in the presence of 1,25-(OH)2D3 displayed a statistically significant down-regulation of allergen-induced expression of IL-13 and IL-17 in CD4+T cells.These results indicated that allergens may induce changes in CD4+T cell function to increase inflammatory cytokine production. 1,25-(OH)2D3 modulated the capacity of CD4+T cells in response to allergens, which might be protective for allergy.

Asthma is the most common chronic inflammatory disorder characterized by cough, wheezing and dyspnea in children. Nutrition is an important factor which influences on induction and exacerbation of asthma. There are controversies to use Vitamin E in asthmatic patients. The aim of this study was to evaluate the effect of vitamin E supplement in children with moderate asthma. This is a randomized double blind placebo-controlled trial performed on children (age 2-17 years old) with moderate asthma (5-17 years old) from March 2010 to March 2012. Case group were treated with fluticasone and vitamin E (50mg/day) and control group received fluticasone plus placebo for 8 weeks. Out of 300 cases, 240 cases completed the study. Female to male ratio was 0.84. Serum level of Vitamin E significantly increased after treatment in intervention group. FEV1 and FEV1/FVC ratio was significantly improved in case group compared to the control group. It can be concluded that vitamin E supplement could improve clinical manifestations and pulmonary function test in children with moderate asthma.

Asthma and gastroesophageal reflux disease (GERD) are two common problems in pregnancy and they affect pregnancy in several ways. In this study, we aimed to evaluate GERD and asthma in pregnant women who referred for prenatal care visits.One-hundred and seventy three pregnant women with a complaint of dyspnea were included in the study. A questionnaire was filled and lung function tests were performed. All patients were visited by a respiratory specialist and questionnaires were evaluated by a gastroenterologist. Out of the total number of women studied, 37% were diagnosed to have asthma and 36.4% were non-asthmatics. Twenty six percent of the pregnant women who had symptoms and signs of asthma with normal spirometry were classified as probable to have asthma. GERD was diagnosed in 80.9% of the pregnant women, but it was not significantly higher in asthmatic or probable asthmatic women compared to non-asthmatic ones. However, severity of GERD was significantly higher in asthmatic pregnant women compared to the others. In conclusion, the prevalence of GERD was quite high in pregnant women, irrespective of the fact that they were asthmatic or non-asthmatic. Further studies evaluating women throughout pregnancy will inform us more about this relationship.

It has been widely thought that diabetic patients are prone to infections due to hyperglycemia induced immunodeficiency; the present study was designed to examine this opinion.In diabetic patients and normal control groups T-cell reactivity to hsp-60 molecule, tetanus toxoid recall antigen (TT) and phytohemagglutinin-A (PHA) mitogen were evaluated The number of circulating IFN-γ, IL-10 and IL-13 cytokine producing cells stimulated with above antigens or mitogen as well as the serum levels of Th1/Th2 type cytokines were determined. Total serum immunoglobulins (IgG, IgA, IgM), C3, C4 and CH50 were also measured.Diabetic patients showed a positive circulating T-cell reactivity to human recombinant hsp60 However, this reactivity was significantly lower in comparison to control group (p<0.001). All other examined factors were not significantly different between diabetic and normal subjects except for the number of IFN-γ and IL-13 producing cells in response to PHA stimulation, which was higher in control gtroup (p=0.006, 0.018, respectively). The mean serum concentration of IgA in diabetic patients was 245.86±115.05 mg/dl versus 192.96±105.33 mg/dl in healthy control group (p<0.018).We were not able to demonstrate any substantial mitigation in cellular arms of immune reaction to some prominent T-cell antigens and mitogens, as well as, in main parameters of humoral immunity of diabetic patients, thus, the common notion of believing that patients with diabetes suffering from immunodeficiency should be revised. It is much more appropriate that “altered immunity“is applied instead of “immunodeficiency” to explain the immunity condition in this group of patients.

Mannan-binding lectin (MBL) is a vital protein of innate immune system and has two critical functions: complement activation through the lectin pathway and opsonization. MBL deficiency has been classified as the most common inherited immunodeficiency known in humans (about 30% of the population), and is associated with predisposition to infections and high risk of some autoimmune diseases. The purpose of this study was to determine the profile of MBL serum level in Iranian healthy population in association with sex and age groups for the first time.We studied the serum concentration of MBL in 593 Iranian healthy cases: 340 males and 235 females in 4 different age groups by using enzyme-linked immunosorbent assay.The mean serum levels of MBL were 3.854± 2.77µg/ml at the age of less than 6 months, 4.147±3.54µg/ml at 6 months to 2 years of age, 4.410±3.09µg/ml at 2-6 years and 2.207±1.73µg/ml in adults. There was significant differences in the mean concentration of MBL among different age groups of children and also between children and adults (p<0.05). No association was observed between sex and MBL concentrations.MBL serum levels of Iranian population seem to be different from some of other populations which may be explained by genetic variations. The MBL values in this study can be used as a normal reference range for future studies in Iranian population.

Increased levels of proinflammatory cytokines have been recorded after the onset of transient or permanent brain ischemia and are usually associated with exacerbation of ischemic injury. Embolic stroke model is more relevant to the pathophysiological situation in such patients, because the majority of ischemic injuries in humans are induced by old thrombi that originate from the heart and carotid arteries. Therefore, the aim of the present study was to investigate changes of inflammatory cytokines after embolic stroke.Rats were subjected to embolic stroke, induced by a natural old clot which was injected in Middle Cerebral Artery (MCA), or sham stroke, which the same volume of saline was injected into the MCA. At 48 h after stroke induction, the levels of 5 cytokines (IL-1α and β, IL-6, IFN-γ and TNF-α) were determined in 500 µg of total protein using the Bio-Plex Rat Cytokine Array (BioRad), according to the manufacturer’s instructions in ischemic and non-ischemic cortices.While stroke animals showed infarctions and neurological deficits, we did not observe any cerebral infarction and neurological deficits in sham-operated animals. The levels of IL-1α (p=0.000) and -β (p =0.004), IL-6 (p =0.008), TNF-α (p =0.000) and IFN-γ (p =0.044) were significantly increased compared to sham treated animals.The findings of the present study suggest that part of ischemic injury in the embolic stroke may be mediated through the increased levels of inflammatory cytokines.

Interleukin (IL)-17-producing T helper (Th)-17 cells have recently been explained as a distinct population of CD4+ T cells which play an important role in immunity against infectious agents. Establishment of persistent phenotype of Th17 cells and recognition of lineage-deviating factors are of most attractive goals in modern researches in immunology. Although IL-6 and TGF-β are frequently used to differentiate naive T cells to Th17 phenotype in mouse models, the application of IL-23 and its importance in preventing cells from plasticity needs to be more investigated. Our main objective was to evaluate the role of IL-23 in Th17 to Th1 plasticity. In this research project, we generated in vitro Myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells in the presence of TGF-β, IL-6, IL-23 and peptide MOG35-55. Th17 development was confirmed by assessment of relevant transcription factors and secreted cytokines by flowcytometry and ELISA, respectively. Th17 to Th1 plasticity was monitored by consecutive samplings in different time points without any extra supplementation of IL-23. Cell culture supernatant was evaluated for Interferon (IFN)-γ secretion and cells were evaluated for intracellular expression of this cytokine. Our results showed that the employed method was relatively convenient in developing antigen-specific Th17 cells. We also showed that IL-23 deprivation which happens by prolongation of culture period, can convert IL-17 producing cells to IFN-γ secreting Th1 phenotype. IL-23 can be considered as a Th17 phenotype stabilizing factor for in-vitro developed lineages.

This paper presents a 54-year-old female with lupus whom severe anaemia due to pure red cell aplasia (PRCA) was the first manifestation. There was seven years interval between PRCA onset and diagnosis of lupus. Thymectomy due to thymoma had been carried out six years before but anaemia sustained. Hypothyroidism and hypoparathyroidism were other associated diseases. Severe anaemia and the need for monthly blood infusions were resolved following treatment with Prednisolone, Hydroxychloroquine and Levothyroxine.