Iranian Journal of Allergy, Asthma and Immunology
Volume:11 Issue: 1, Mar 2012

CD40 is recognized as a member of tumor necrosis factor receptor super family. It is expressed by the immune and non-immune cells. Its interaction with CD40 ligand (CD154) brings about a regulatory effect on the cellular and humoral immunity. The pathway of CD40-CD154 is influential in various diseases. Investigations on such diseases have revealed dimensional mechanisms whereby this route intensifies host protection. Moreover, through these mechanisms, pathogens subvert the signaling of the CD40, conditions in which the CD40-CD154 pathway promotes disease and also through the relevant modulation for immunotherapy. This review focuses on the role of CD40-CD40L (CD154) interactions in dendritic cells (DCs) regulation, tolerogenic dendritic cells, role of CD40 in autoimmune disease, allograft rejection and induction of tolerance by down regulation of CD40. According to these roles, it is assumed that CD40 is a functional molecule in the pathologies of conditions like autoimmune diseases and allograft rejection caused by activated T and B cells.

The non-classical MHC class-I mainly involves in the regulation of innate immune responses where HLA-E plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated the effect of HLA-E polymorphisms on post-hematopoietic stem cell transplantation outcomes. The study group included 56 donor-patient pairs with underlying malignant hematological disorders undergoing HLA-E matched allogeneic hematopoietic stem cell transplantation. They were genotyped for HLA-E locus using a sequence specific primer-polymerase chain reaction. The median follow-up was 20.6 months (range 0.2-114.8) and the parameters assessed were acute and chronic graft-versus-host disease and overall survival. We showed a lower frequency of acute graft-versus-host disease (grade II or more; p=0.02) and chronic graft-versus-host disease (extensive; p=0.04) in the patients with HLA-E*0103/0103 genotype compared to other genotypes of HLA-E. There was also an association between HLA-E*0103/0103 and improved overall survival (p=0.001). Conclusively, our results suggest a protective role for HLA-E*0103/0103 genotype against acute graft-versus-host disease (grade II or more) and chronic graft-versus-host disease (extensive) as well as an association between this genotype and a better overall survival after HLA-E matched allogeneic hematopoietic stem cell transplantation.

Asthma is one of the most common chronic inflammatory disorders in children. Nonadherence to medical therapy is a major cause of poor clinical outcome the objective of this study was evaluating factors, which are resulted in nonadherence to medical therapy in children with asthma.In this descriptive study, 150 children with asthma and nonadherent to medication therapy were enrolled. General information and probable causes of nonadherence were recorded in self-report questionnaire and data were analyzed. In our study, 57.3% of children were male. Approximately 43%of children belonged to age group 6-9 years old. Prevalence of probable causes of nonadherence to treatment were concern about treatment expenses(34.7%), fear of cardiac complications(34.7%), concern about drug dependency(38.7%), belief to growth inhibition(30.7%) and fear of osteopenia (32%). There was statistically significant reverse association between treatment with multi-drug regimens and concern about bone mineral abnormalities, cardiac complications and drug dependency (p=0.0001, 0.014 and 0.012 respectively). In addition, there was a significant association between mild asthma and fear about drug dependency (p=0.001).According to our results, factors such as prolonged duration of treatment, various therapeutic regimens, and receiving multiple drugs before diagnosis of asthma pose the highest frequencies for nonadherence.

Cow's milk anaphylaxis is the most common food-induced anaphylaxis in Iranian children. The clinical and laboratory findings of cow's milk anaphylaxis are evaluated in this study. All children who had experienced cow's milk anaphylaxis and had been referred to Immunology, asthma and allergy research center during a 5-year period were considered. After fulfilling a questionnaire, patients underwent measurement of total IgE and cow's milk-specific IgE by Immunocap test and Skin prick test (SPT) with cow's milk extract. Patients with a convincing history and one positive cow's milk-specific IgE test (SPT or Immunocap test) and patients with both positive tests were enrolled, in this study.Out of 49 patients, 59.2% were male. Patient's mean age was 5 years old and their mean age at the time of first attack was 5.7 months (SD = 4.3). Most of the patients have experienced more than one episode of anaphylaxis (79.5%) and in 85.7% of all cases, first attack occurred during the first year of life. Severity grading 1-5 were 2%, 6.1%, 18.4%, 69.4%, 4.1% respectively. Most common manifestations were cutaneous 98%, Respiratory 91.8%, Gastrointestinal 55.1%, Cardiovascular 46.9% and neurologic 46.9% signs and symptoms respectively. Twenty four patients showed positive SPT. Mean total IgE was 239.6±3.3 (IU/mL) and mean cow's milk-specific IgE was 19.28±27.2 (IU/mL). Most patients showed reactions only after ingestion of cow's milk or after dairy foods (81.6%).It is concluded that cow's milk anaphylaxis may happen early in life. Regarding the severity of attacks and remarkable number of patients with several attacks, poor knowledge about this disorder is evident.

Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with abnormal cytokine production, and activation of T-helper 2 cells. The aim if this study was to determine whether cytokine gene polymorphisms might influence the development of AD. Single nucleotide polymorphisms in the genes for I-L1alpha, IL-1beta, IL-1R, IL-2, IL-4, IL-6, IL-10, IL-12, TGF beta, TNF and IFNgamma were investigated by PCR and sequence specific primers in Macedonian patients with AD (67 children, age of 6 months to 5 years) and 301 normal unrelated individuals. Susceptible cytokine polymorphisms for AD for eleven genotypes (IL-4 -33/T:T IL-4 -1098/G:G, TGFbeta cdn25C:G, IL-4 -1098/T:T, IL-1alpha -889/C:T, IL-2 +166/T:T, IL-1beta -511/C:T, IL-12 -1188/C:T, IL-10 -1082/A:G, IL-1beta +3962/C:T, IFNgamma +874/A:T), five diplotypes, six haplotypes, and for alleles were found. Protective cytokine polymorphisms for AD for seven cytokine genotypes (IL-4 -1098/G:T, TGFbeta cdn25/G:G, IL-4 -33/C:C, IL-1alpha -889/C:C, IFNgamma +874/A:A, IL-10 -1082/A:A, IL-1beta -511/C:C), one cytokine diplotypes, two cytokine haplotypes, and four cytokine alleles were also found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with AD in population of Macedonians.

Severe Congenital Neutropenia is one of primary immunodeficiency disorders that characterized by severe neutropenia and is associated with severe systemic bacterial infections from early infancy. Granulocyte Colony Stimulating Factor (GCSF) is clinically used as a treatment for congenital and acquired neutropenia. The aim of this study was evaluation of GCSF (PD- Grastim) in treatment of these patients. Patients with severe congenital neutropenia referred to Immunology, Asthma and Allergy Research Institute between Jan 2007 and Dec 2010 enrolled the study. Other causes of neutropenia were excluded by serial CBC and bone marrow studies, medical and drug histories and immunological tests. Patients were visited and examined monthly to evaluate their CBC and ANC (Absolute Neutrophil Count), GCSF side effects and dosage adjustment. Cytogenetic studies were being done for all the patients for early detection of progression to AML/MDS. From twenty two patients who enrolled this study, 16 patients regularly evaluated. They were ten males and six females, range in age from 2 to 18 years old. Two patients failed to continue our follow up unfortunately and four patients died due to disease complications. Patients were followed for 24 to 48 months. In a period of 12-24 months before treatment, the mean of hospitalization frequency was 3.1 times and duration was 10 days; while during receiving treatment, they decreased to 0.2 times and 3 days, respectively (p<0.01). Also significant increase in mean ANC was observed during follow up (315/µl before treatment versus 1749/µl after 12 month regular treatment). Bone pain was the most common side effect. There have been no evidences of developing AML/MDS up to present time. Treatment with GCSF significantly reduced the duration and the frequency of hospitalization. Because of plausible progression to AML/MDS, regular follow-up of patients should be continued.

Primary immunodeficiency diseases (PIDs) consist of a group of genetic disorders that predispose the patients to immune-mediated complications. The aim of this study was to assess the knowledge of Iranian general practitioners and pediatricians about PIDs.A questionnaire consisting 52 closed questions on clinical symptoms, laboratory data, associated syndromes and management of PIDs patients was made valid and reliable by a pair pilot study. Then the questionnaire was filled by pediatricians, general practitioners and pediatric residents from different regions of Iran. Totally, 333 physicians (50 general practitioners, 52 pediatric residents, 182 pediatric specialists, and 49 pediatric sub specialists) participated in this study. The mean total score was 55.9±14.3 (i.e. about 29 correct answers out of 52 questions). One hundred and five participants (31.9%) answered correctly more than two third of all questions. In order to qualitatively compare the groups a ranking system was used. Total scores was significantly different between physicians groups (p<0.01). Pediatric subspecialties gained the highest rank, which was significantly over the other participants (p<0.05). This study showed that there is a considerable lack of awareness on PIDs in physicians. This may be one of the major reasons in late diagnosis and the delay in adequate treatment deteriorating patient's morbidity and mortality. Retraining classes and reconsidered educating schedules are needed as an efficient strategies and improving physician's knowledge about PIDs.

Chronic obstructive pulmonary disease (COPD) and asthma are major public health problems, which seems to have close association with psychiatric disorders. The present study was conducted to compare the psychological status between asthmatic and COPD patients and clarify the relationship with severity of pulmonary obstruction. This cross-sectional study was planned to compare the psychological status in 67 stable obstructive lung patients (17 asthma, 24 asthmatic bronchitis and 26 COPD) referred to respiratory clinic of Ghaem hospital and 33 healthy controls, in Mashhad city, north east of Iran. Severity of pulmonary obstruction was determined based on GOLD criteria. "Beck Depression Inventory", "Hamilton Anxiety Rating Scale" and "SCL-90-R" questionnaires were used to determine the psychological status. Prevalence of general psychopathology in asthma, COPD, asthmatic bronchitis and control groups were 64.7%, 42.3%, 33.3% and 36.4% respectively. Psychological status was directly related to severity of pulmonary obstruction (p=0.048), Prevalence of depression in asthmatic, COPD and asthmatic bronchitis groups were 66.7%, 54.2% and 44.4% respectively. Depression score was related to severity of pulmonary obstruction (p=0.000).Prevalence of anxiety in asthma, COPD and asthmatic bronchitis were 46.7%, 45.8% and 40.7% respectively. Anxiety score was related to marital status and satisfaction with income Asthmatic and COPD patients are at equal risk of developing psychiatric disorders and both require psychological evaluations in respiratory clinics. Therapists must pay more attention to patients with severe pulmonary disease

Many patients with atopic eczema (AE) would "march" to develop allergic rhinitis (AR) and asthma. Physicians, patients and their families often do not appreciate the significance of these diseases as co-morbidities of atopy.The aim of this study was to evaluate the prevalence and severity of airway atopies in patients with AE. AR and asthma severity were assessed in consecutive AE patients seen at a pediatric dermatology clinic by ARS (allergic rhinitis score) and ACT (asthma control test). Eczema severity (SCORAD and Nottingham Eczema Severity Score: NESS) were recorded.110 patients with AE and 42 patients without AE were recruited. Allergic rhinitis and asthma were significantly more prevalent in patients with AE [odds ratio for AR was 2.9 (CI: 1.3 - 6.5) and for asthma 4.3 (CI: 1.3 - 16.10)]. 23 (45%) of the AE patients with AR reported that they were currently on oral antihistamine whereas none of the non-AE group reported such usage. Both groups reported relatively higher sneezing and nasal congestion scores and low "eye watering" score. Comparing mild with moderate-to-severe AE, there was essentially no difference between the prevalence of allergic rhinitis and asthma, or severity of symptoms by ARS and ACT, but females reported more severe symptoms of sneezing and itching nose.We conclude that allergic disorders of airway are very common among AE patients independent of the eczema severity. Most of the patients have mild-to-moderate AR and asthma. There is a lot of room for parent/patient education, and childhood eczema may prompt early awareness of these airway co-morbidities of atopy.

Occupational asthma has been reported to be the most common chronic respiratory occupational disease in many developed countries, and as with other occupational lung diseases, occupational asthma is potentially preventable. We report the case of a 24-year-old baker who experienced pneumomediastinum as a consequence of workplace exposure. This is the first report of pneumomediastinum as an acute complication of occupational asthma, and it exemplarily shows that the lack of medical surveillance at the workplace may lead to an acute, although unusual, complication.