Iranian Journal of Allergy, Asthma and Immunology
Volume:7 Issue: 4, Dec 2008

Rheumatoid arthritis is a disease associated with painful joints that affects approximately 1% of the population worldwide, and for which no effective cure is available. It is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion. Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. TNF-α overproduction is thought to be the main contributor to increased ROS release in patients with RA. Increased ROS production leads to tissue damage associated with inflammation. The prevailing hypothesis that ROS promote inflammation was recently challenged when polymorphisms in Neutrophil cytosolic factor 1(Ncf1), that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. It has been shown that oxygen radicals might also be important in controlling disease severity and reducing joint inflammation and connective tissue damage. In this review article, our aim is to clarify the role of ROS in immunopathogenesis of Rheumatoid arthritis.

A wide range of biological activities of garlic in vitro and in vivo have been verified including its antioxidant, antitumor and anti-inflammatory effects. Indoleamine 2,3-dioxygenase (IDO) is an enzyme widely distributed in mammals and is inducible preferentially by IFN-γ. IDO degrades the essential amino acid tryptophan to form N-formyl kynurenine. In the present in vitro study, the modulatory effect of 14kDa molecule isolated from garlic on IDO induction was tested. Cultures of mononuclear cells were exposed to 14kDa garlic fraction. Then, their proliferation responses and IDO metabolites were measured. A significant down-regulatory effect of garlic on IDO activity was found and also the proliferation responses of mononuclear cells increased. If these results are verified in vivo, an explanation will be provided on how garlic may interfere in IDO induction, which paves the way for elucidating its specific therapeutic effect in preventing tumor progress.

Selective IgA deficiency (IgAD) (serum IgA concentration of <0.07 g/l) is the most common primary immunodeficiency in Caucasians, with an estimated prevalence of 1/600. There are strong indications for involvement of genetic factors in development of the disease and the frequency of several extended major histocompatibility complex haplotypes (including HLA-A1, B8, DR3, DQ2) have previously been shown to be increased among Caucasian patients with IgAD.PCR was used to type HLA B, DR, and DQ alleles in 29 Iranian individuals with IgAD and 299 Swedish individuals with IgAD. The results indicate a strong association with the HLA B14, DR1 alleles in Iranian subjects and HLA B8, B12, B13, B14, B40, DR1, DR3, DR7, DQ2 and DQ5 alleles in Swedish subjects.Differences in HLA association of IgAD in Iran and Sweden confirm the notion of a genetic background of the disease and that multiple, potentially different genes within the MHC region might be involved in the pathogenesis of IgAD in different ethnic groups.

Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms (75 males and 37 females) were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients (4.5% vs. 0%, P-value=0.04). HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls (10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively). The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 (Pc=0.03) and HLA-DQB1*0603 (Pc=0.0015). Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls (7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively). The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201.These data suggests that HLA-DRB1, DQA1 & DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen.

Though intravenous (IV) Magnesium Sulphate (MgS04) has additive effect to beta-2 agonists, its additive benefit in face of combination therapy with beta-2-agonists and ipratropium (standard therapy of severe acute exacerbation of asthma) remains unaddressed. The aim of this investigation was to evaluate the role of IV MgSO4 when used as an adjunct to standard therapy of severe exacerbations of asthma. Randomized, single blinded, placebo-controlled study was carried out in Emergency Department (ED). Patients aged 18-60 years presenting with acute asthma and FEV1 < 30 % predicted (pred.) were included. All patients received IV Hydrocortisone on arrival. In group1 (controls), patients were nebulised with salbutamol and ipratropium thrice at 20 minutes interval and were given 2g IV MgSO4 at 30 minutes. In group2 patients were nebulised similarly, but were given IV normal saline at 30 minutes for blinding. FEV1 was evaluated at baseline and at 30 minutes intervals. The primary efficacy end point was FEV1%pred. at 120 mins and pooled discharge rate (derived from comparing proportion of groups attaining PEFR >60%pred. and relief in dyspnea at 30, 60, 90, 120 minutes). Both groups of 30 patients each, were matched with respect to demographic and pulmonary parameters (Baseline FEV1%: 22.0+5.1% in group2 vs.22.07+5.2% in group1, p=0.87).At 120 minutes, there was a higher mean FEV1 %pred (62.84+4.73% vs. 56.7+4.5%) and %improvement from baseline of (40.7+9.2%vs34.77+7.3%), in group 2 as compared to group1 (Mean Difference= 6.07%, C.I.1.87-10.62., p<0.01).The pooled discharge rate in group2 with respect to group1 was positive and significant (log rank.=6.8, p<0.05). Thus IV MgSO4 improves pulmonary function and discharge rates, when used as an adjunct to standard therapy in severe acute asthma. Magnesium sulfate as an adjunct to standard therapy in patients with severe exacerbation of asthma could cause improvement in pulmonary function and decrease in hospital admission.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to recurrent infections, autoimmunity and malignancies. We have previously shown that some pediatric patients with CVID can respond to meningococcal polysaccharide vaccine. Twelve pediatric cases with CVID were re-evaluated to determine whether bactericidal antibody responses or IgM memory B-cells correlate with the severity of disease resulting from the deficiency. We found that bronchiectasis and clinical manifestations of autoimmunity occur more commonly amongst non-responders to vaccine. In contrast, low populations of memory B-cells do not correlate with these sequelae. The results of this study could help pediatricians plan strategies for prevention of sequelae in children presenting with CVID.

In chronic granulomatous disease (CGD) patients, esophageal stricture is a rare complication and the treatment of choice is still controversial. There are few reports of successful therapy with antibiotics, corticosteroids, multiple balloon dilatations or their combination. We report a 3-three-year-old Iranian boy with recurrent esophageal obstruction due to CGD. The patient transiently responded to dilatation in one occasion and at another time to short term steroid therapy. We observed an excellent response when long term and high dose of corticosteroid was administered. It showed that a long term and high dose steroid therapy is more effective than a short term in a patient with CGD and esophageal stricture.

Toxic epidermal necrolysis is a potentially life-threatening disease, which needs necessary treatment. We present a 12 years old female who was a known case of idiopathic generalized tonic-clonic convulsion and presented with fever, diarrhea and generalized erythematous eruption after 2 weeks of being under treatment with maintenance doses of Lamotrigine (LTG) and Valproate (VPA). The eruption led to more than 90% epidermal detachment of the total body surface area. However, she made a full recovery with few negligible sequelae regarding the severity of her disease and the symptomatic therapy and Intravenous Immunoglobulin (IVIG) administration which started soon after the bullae appeared. While IVIG might be beneficial in the treatment of TEN, controlled studies are needed to evaluate the efficiency of IVIG compared to other modalities.