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Abstract Introduction  Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients. Patients and Methods  The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers. Results  The most frequent genotypes in our patients were TNF-α GA at position −308 (P = 0.001), TNF-α AA at position −238 (P = 0.01), IL-1α TC at position −889 (P = 0.0001), IL-1β TC at position −511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-α GG at position −308 (P = 0.001), IL-1α CC at position −889 (P = 0.005), IL-1β CC at position −511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-α (positions 308, −238) was A/A in the patient group in comparison with controls (P = 0.0001). Conclusion  While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-α AG genotype (−308), it seems that the production of TNF-α in the asthmatic patients could be higher than normal subjects. [ABSTRACT FROM AUTHOR]

Abstract  Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections, autoimmunity, and malignancies. Twenty-five cases with CVID (18 male and 7 female) and 25 healthy volunteers were investigate in this study. Soluble CD30 (sCD30) serum levels of the subjects were measured and compared. Serum levels of sCD30 in the patients with CVID were significantly increased in comparison with controls (36.93 ± 32.38 vs 5.27 ± 1.32 U/ml, P P = 0.010). High levels of sCD30 in the CVID patients with splenomegaly and the presence of lymphoma in a patient with the highest level of sCD30 may suggest a soluble form of this marker as a prognostic tool in such diseases. [ABSTRACT FROM AUTHOR]

Abstract  Severe congenital neutropenia (SCN) is a rareE primary immunodeficiency disorder characterized by early onset recurrent infections in association with persistent severe agranulocytosis. To identify the clinical, immunohematological, and molecular characteristics of patients with SCN, 18 Iranian patients with the mean age of 8.8 � 5.8 years were investigated in this study. All of these patients experienced severe neutropenia; the mean of absolute neutrophil count was 281.4 � 137.7 cells/mm3. Bone marrow findings were typified by a myeloid maturation arrest at the promyelocyte–myelocyte stage in these patients. Molecular analysis revealed different mutations in the ELA-2 gene of one patient and in the HAX-1 gene of another three patients. The most common presenting complaints in these patients were superficial abscesses, oral ulcers, cutaneous infections, omphalitis, and pneumonia. During the course of illness, all patients developed mucocutaneous manifestations, and 16 cases had respiratory infections. The most commonly manifestations were abscesses, oral ulcers, pneumonia, periodontitis, otitis media, cutaneous infections, mucocutaneous candidiasis, and acute diarrhea. Three patients died because of a severe infection. Although SCN is a rare disorder, early onset of severe and recurrent infections should always raise a suspicion, which deserves further evaluation for detecting such disorder. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disorder of the airways, associated with airway remodeling and hyperresponsiveness. It is expressed that asthma influences about 300 million people around the world, which is estimated to increase to about 400 million by 2025. The prevalence rate is 15 to 20 percent in children and 5 to 10 percent in adults, while its trend is still increasing. Inflammation plays an important role in the pathophysiology of asthma, which involves an interaction of different types of the immune cells and mediators. It leads to a number of pathophysiology changes, including bronchial inflammation, airway obstruction, and clinical episodes such as cough, wheeze and shortness of breath. Asthma is now greatly being introduced as a heterogeneous disorder and it is pointed out to the role of T cells, including Th1, Th2, Th17, and regulatory T cells. Other immune cells, especially neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been recognized in clinical samples and mouse models of asthma. Different cytokines, including pro-inflammatory cytokines (such as TNFa, IL-1, and IL-6), T helper 2 cytokines (such as IL-4, IL-5, IL-9, IL-13), and growth factors (such as GM-CSF, PDGF) play a role in the pathogenesis of asthma. Indeed chemokines (such as MPC-1, RANTES , MIP-1) and the chemokine receptors (such as CCR3, CCR4, CCL11, CCL24, and CCL26) play an important role in the recruitment of circulating inflammatory cells into the airways in asthmatic patients and also is related with increased T helper 2 cytokines after inhaled allergens. Among new approaches, treatment of asthma with anti-cytokine drugs such as antibodies blocking IL-4, IL-5, IL-9 could reduce recruitment inflammatory cells into the airways and remodeling. The final perspective of asthma treatments would be to alter from the symptomatic treatments to disease modifying. [ABSTRACT FROM AUTHOR]

Abstract Introduction  Pemphigus vulgaris (PV), an autoimmune disease affecting the skin and mucous membranes, is associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. Materials and Methods  In order to evaluate the association of HLA-DR and DQ alleles and haplotypes in Iranian non-Jewish patients with PV, 52 patients with PV and 180 normal subjects as control group were investigated in this study. Results and Discussion  HLA-DRB1*04, -DRB1*1401, -DRB4, -DQA1*0104, -DQA1*03011, -DQB1*0302, and -DQB1*0502 alleles have been significantly increased in our patients group. Moreover, the haplotypes HLA-DRB1*04/-DQA1*03011/-DQB1*0302 and HLA-DRB1*1401/-DQA1*0104/-DQB1*0502 increased significantly in our patients. In contrast, the following alleles decreased significantly in our patients: HLA-DRB1*15, -DRB1*0301, -DRB1*07, -DRB1*11, -DRB5, -DQA1*0101, -DQA1*0103, -DQA1*201, -DQA1*05, -DQB1*0201, -DQB1*0301, -DQB1*06011, and -DQB1*0602. In addition, HLA-DRB1*15/-DQA1*0103/-DQB1*06011, HLA-DRB1*0301/-DQA1*05011/-DQB1*0201, HLA-DRB1*07/-DQA1*0201/-DQB1*0201, and HLA-DRB1*11/-DQA1*05/-DQB1*03011 decreased significantly in our patients. Genetic factors are involved in the occurrence of PV; HLA-DRB1*04 and -DRB1*1401 alleles and the related haplotypes are suggestive to be two major PV susceptibility factors in our population study. [ABSTRACT FROM AUTHOR]

Abstract  This study focuses on endoscopic and pathologic alterations of gastrointestinal (GI) disorders of Iranian patients with common variable immunodeficiency (CVID). Nineteen of 39 CVID patients (48%) had GI complaints. The most common symptom was chronic diarrhea (28%). In endoscopic examination of small intestines, 15 patients had no abnormal finding. Duodenal biopsy revealed villous atrophy in eight and nodular lymphoid hyperplasia in three patients. There was no statistically significant difference between patients with and patients without duodenal villous atrophy regarding the presence of chronic diarrhea, anemia, and absolute CD4 cells. In three patients, biopsies of the colon showed chronic noncrypt-destructive colitis. GI problems pose a high morbidity to CVID patients and are second only to respiratory complications. CVID patients are at increased risk of infectious and inflammatory conditions in the GI tract. Early diagnosis of these complications improves the quality of life and well-being of patients. [ABSTRACT FROM AUTHOR]

Local protein synthesis in neuronal dendrites is critical for synaptic plasticity. However, the signaling cascades that couple synaptic activation to dendritic protein synthesis remain elusive. The purpose of this study is to determine the role of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling in regulating dendritic protein synthesis in live neurons. We first characterized the involvement of various subtypes of glutamate receptors and the mTOR kinase in regulating dendritic synthesis of a green fluorescent protein (GFP) reporter controlled by αCaMKII 5′ and 3′ untranslated regions in cultured hippocampal neurons. Specific antagonists of N-methyl-D-aspartic acid (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and metabotropic glutamate receptors abolished glutamate-induced dendritic GFP synthesis, whereas agonists of NMDA and metabotropic but not AMPA glutamate receptors activated GFP synthesis in dendrites. Inhibitions of the mTOR signaling, as well as its upstream activators, phosphatidylinositol 3-kinase and AKT, blocked NMDA receptor-dependent dendritic GFP synthesis. Conversely, activation of mTOR signaling stimulated dendritic GFP synthesis. In addition, we also found that inhibition of the mTOR kinase blocked dendritic synthesis of the endogenous αCaMKII and MAP2 proteins induced by tetanic stimulations in hippocampal slices. These results identify critical roles of NMDA receptors and the mTOR signaling pathway for control of synaptic activity-induced dendritic protein synthesis in hippocampal neurons. [ABSTRACT FROM AUTHOR]

Background/Aims: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. Methods: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. Results: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 μg/mL vs 219.8±59.0 μg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. Conclusions: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods. [ABSTRACT FROM AUTHOR]

Primary immunodeficiency disorders (PID) are a heterogeneous group of disorders, characterized by an unusual increased susceptibility to various infections. In order to study the frequency of PID in Turk ethnic group of northwestern Iran, this study was performed. Fifty-nine PID patients (36 male and 23 female) with a mean age of 5.3 years (median: 3 years; range: [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia, defective specific-antibody production resulting in recurrent bacterial infections. Delay in diagnosis and inadequate treatment result in increased irreversible complications and mortality. To determine persistent morbidities, mortality rate and survival in Iranian patients with CVID, hospital records of 72 (39 males and 33 females) diagnosed CVID patients were reviewed. Probabilities of survival after diagnosis of CVID were estimated from Kaplan–Meier life tables.Studied patients were enrolled over a 20-year period (1984–2005). The most commonly observed complication was bronchiectasis (24 cases), followed by splenomegaly, intestinal villous atrophy (11 cases), and failure to thrive (10 cases). Post-diagnosis survival was estimated as 65% for the first 6.5 years, which remains the same until 14 years after diagnosis when the survival curve drops to nearly 45%. The mortality rate among patients who had no regular visits and did not receive periodical IVIG was more remarkable when compared with those who had been followed up timely (p-value = 0.001).The most common cause of death was respiratory failure. Based on our observation, it can be highlighted that all patients with CVID, even under regular immunoglobulin replacement, need close monitoring for early detection of complications and introduction of appropriate management. [ABSTRACT FROM AUTHOR]