Iranian Journal of Allergy, Asthma and Immunology
Volume:12 Issue: 4, 2013 Aug

Multiple sclerosis (MS) is an autoimmune disease characterized by recurrent episodes of demyelination and axonal lesion mediated by CD4+ T cells with a proinflammatory T helper (Th)1 and Th17 phenotypes, macrophages, and soluble inflammatory mediators. The overactive pro-inflammatory Th1 cells and clonal expansion of B cells initiate an inflammatory cascade with several cellular and molecular immune components participating in MS pathogenic mechanisms. In this scenario, autoantibodies and autoantigens have a significant role in immunopathogenesis, diagnosis and therapeutic targets of MS. In this review, we try to introduce the autoantigens and autoantibodies and explain their roles in pathogenesis of MS.

The aim of this study was to evaluate the sensitivity of the population of Fez and Casablanca in Morocco to dry white beans (Phaseolus Vulgaris) and to investigate the effect of food processing (heat and/or enzymatic hydrolysis by pepsin) on this sensitivity. Work was based on a bank consisting of 146 sera from patients with atopic hypersensitivity in order to evaluate specific immunoglobulin E (IgE) levels to native and processed white bean proteins by ELISA. Under the same conditions, we assessed the immunoreactivity of rabbit IgG obtained by immunization with native white bean proteins.Evaluation of specific IgE to the white bean proteins showed that 51% of children and 39% of adults had positive values. The heat treatment and pepsin hydrolysis of dry bean proteins showed a reduction of 68% of IgE binding recognition in more than 65% ofall patients. After heating, all patients indicated a reduction greater than 36%. With rabbit IgG, we observed a decrease by 25% of binding under heat treatment while enzymatic digestion reduced IgG recognition by 46.6%.These findings suggest that epitopes recognized by IgE in the studied population were conformational sites whereas those recognized by rabbit IgG were probably sequential. In conclusion, these results demonstrate that the Moroccan population was very sensitive to white beans and this sensitivity could be reduced after heat treatment or enzymatic hydrolysis.

“Broussonetia papyrifera” (Chinese mulberry) pollen is an important source of allergens in regions surrounding Shanghai, China. To identify and purify major allergens from “B. papyrifera” pollen that reacted with serum antibodies from sensitized patients, “B. papyrifera” pollen was defatted, dried, and extracted proteins were separated using SP cationic exchange or Q anionic exchange columns.Serum samples from 29 allergic patients and 4 healthy controls were collected. Allergens in eluted fractions were identified by Western blot and enzyme-linked immunosorbent assays (ELISA) using serum samples. An inhibitory assay was used to verify allergen-specific antiserum specificity.Serum IgE of 2 patients reacted with a 15 kDa protein band. The protein was eluted with 0.1M NaCl from a SP cationic exchange column. Serum samples from the same patients positively reacted with ELISA plate coated with partially purified 15 kDa protein. Serum IgE of 11 patients reacted with a 72 kDa protein band. The protein was eluted with 0.3M NaCl from a Q anionic exchange column. Serum samples from five patients positively reacted with ELISA coated with partially purified 72 kDa protein.Our preliminary purifications identified two proteins of 72 kDa and 15 kDa as allergens derived from “B. papyrifera” pollen, which reacted with allergic patients’ serum IgE.

The aim of this study was to assess the role of HLA-B*27 and it’s subtypes in determining severity and clinical manifestations of ankylosing spondylitis (AS).A total of 163 AS patients were assessed for clinical manifestations and severity using structured questionnaires. HLA-B*27 screening and B*27 sub-typing were performed by PCR.One hundred twenty two patients (74.8%) were B*27 positive. The male to female ratio, peripheral arthritis, steroid use, intense dorsal kyphosis and decrease of cervical slope had a significantly higher frequency in B*27 positive patients compared to B*27 negative ones (p=0.01, 0.001, 0.01, 0.04 and 0.04, respectively). However, the age of diagnosis was significantly lower in B*27 positive patients (p=0.005). Trend in uveitis and some severity markers including: BASMI and ASQoL were toward higher values in B*27 positive group with no significant difference. After controlling confounding variables, significant relationship was found only between B*27 and BASMI (p=0.01). B*27 subtypes in patients were included B*2705: 48.4%, B*2702: 42.6%, B*2704: 5.7% and B*2707: 3.3%. No significant differences were seen for severity markers and clinical manifestations between subtypes; although trend toward lower values of severity markers, less intense dorsal kyphosis and less decrease of cervical slope were observed in B*2704 and B*2707 versus other polymorphisms.Clinical features and severity of AS is influenced by HLA-B*27. Trend toward higher severity markers in B*2705 and B*2702 versus other polymorphisms might be subject of interest for evaluation in other ethnicities with concentration to other novel susceptibility genes co-inherited in each B*27 subtype.

Stem cells from human exfoliated deciduous teeth (SHED) have been introduced recently and possess characteristics similar to mesenchymal stem cells (MSCs). Because of their convenient accessibility and safety of harvest, SHED can be a preferable source for the ever-increasing MSCs’ applications While they are new, their immunoproperties have not been adequately studied. In this study, we aimed to explore the effect of SHED on T lymphocytes and compare it to conventional MSCs (BMMSCs).At first the isolated T lymphocytes were activated specifically/nonspecifically in vitro and cocultured with SHED or BMMSCs under the same conditions, subsequently their proliferation and cytokine secretion (IL-2 and IFN-γ) were measured.In our experiment, BMMSCs and SHED inhibit the proliferation and cytokine production of both PHA and alloantigen stimulated T lymphocytes in a dose-dependent manner. In direct and indirect contact to T lymphocytes, the inhibition of BMMSCs (but not of SHED) was significantly different The cytokine production from activated T cells was affected differently by two types of MSCs. The inhibition decreased by the separation of lymphocytes and MSCs by a semipermeable membrane, but it was not abolished.This study showed that SHED suppress the activation of human T lymphocytes in vitro like other MSCs. Compared to BMMSCs, this suppression was alleviated. In the equal conditions, the pattern of immune-modulation of BMMSCs and SHED was different, suggesting that SHED do not exert the exact mechanisms of BMMSCs'' immunosuppression., This finding should be verified by further studies focused on the detailed mechanisms of the immunomodulation of SHED and also BMMSCs.

Cytokines play a part in pathogenesis of periodontitis via inflammation phenomenon. Aggressive periodontitis (AgP) is a multifactorial disease resulting in rapid tooth loss due to severe destruction of tooth supporting apparatus. Recently, researchers have focused on genetic susceptibility of periodontitis through investigating the gene variations of cytokines and other components of immune response. In this study we analyzed single nucleotide polymorphism (SNP) of two cytokines in association with AgP in an Iranian-khorasanian population; Interleukin-1 beta (IL-1β) +3954 C/T and Tumor Necrosis Factor alpha (TNF-α) -308 G/A. From arm vein of patients (n=58) and periodontally healthy individuals (n=60) blood sample was obtained and the DNA was extracted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) procedure was performed to recognize the SNPs. X2 test was used to determine the statistically significant differences between the two groups. The frequency of genotypes and alleles had no significant differences between patients and control groups. The distributions were as follows. IL-1β +3954: CT, CC and TT genotypes in patients were 39.6%, 60.4% and 0.0% and in controls were 41.7%, 50% and 8.3%, respectively. TNF-α -308: GA, GG and AA genotypes in patients were 44.8%, 41.4% and 13.8% and in controls were 46.7%, 50% and 3.3%, respectively.This investigation do not substantiates the role of IL-1β +3954 and TNF-α -308 polymorphisms, separately, as risk determinants for AgP in Iranian population. Further research based on all components of immune response, is needed to corroborate the genetic susceptibility of AgP.

Hepatitis B vaccination is safe and effective, although breakthrough infection occasionally occurs in those who receive the vaccine and hepatitis B immunoglobulin (HBIg) prophylaxis. Sequence variation in their antigenic regions is one of the most powerful strategies that are used by viruses to escape recognition by B and T cell-mediated immune responses. The aim of this study was to explore the mutational profile of HBV in vertical transmission.Six HBsAg-positive mothers and their children who developed HBV infection despite immunoprophylaxis were enrolled. After extraction of HBV DNA from sera, the full HBV genome or surface gene was amplified by Gunther and hemi-nested PCR, respectively. After sequencing, the mutational analysis on paired samples between mothers and children were carried out and compared.Different mutations were found in four children, at least, one arose in functional and/or immune epitope activities. Of 30 amino acid changes, 11 (36.6%) were located within the known HBV immune epitopes. In three children, mutations occurred within the “a” determinant region, one mutation (B2) was identical to the mother of patient, an indication of vertical transmission. The other two (B4 and B5) were considered as vaccine escape mutations. Three children harbored wild-type HBsAg, similar to their mothers. Regarding transmission in infected children, the immunoprophylaxis had no effect and failure of vaccination was observed in 2 isolates.These findings emphasized the need for an alternative regimen, such as the administration of boosters or a more effective HBV vaccine for high-risk children who are born to HBsAg-positive mothers.

It is well accepted that in experimental model of Leishmania major infection, BALB/c mice mount a Th2 response and produce IgG1 predominantly whereas C57BL/6mice enhance Th1 response with the biased production of IgG2a antibodies. Therefore, screening for parasite antigens on the basis of reactivity with sera from infected susceptible or resistant mice might be used for the identification of Th1- or Th2-inducing antigens.In this study, the antigenic profile of Leishmania majoramastigote that induce IgG1 or IgG2a isotypes in infected BALB/c or C57BL/6 mice were compared.Western blot analyses revealed that 27, 40, 43, 45 and 114 kDa proteins elicited IgG1 and not IgG2a in both BALB/c and C57BL/6 mice and 55 kDa protein was recognized exclusively by IgG1 of BALB/c mice sera. On the contrary, the bands corresponding to proteins with molecular weights (MW) of 30, 35, 52, 58 and 66 were intensively immunostained with IgG2a from C57BL/6 mice which made them potential candidates for eliciting Th1 response.In conclusion, the results showed that the generation of the immune responses depended on the mouse strain and some leishmanial antigens had an intrinsic potency to elicit Th2 responses.

It was recently demonstrated that 5-(5-nitrofuran-2-yl)-1, 3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents are effective in vitro against Leishmania major.Following on this evidence, we used colorimetric assay of acid phosphatase activity in the promastigotes as an indicator for cell viability. Also we studied the effect of these compounds on induction of nitric oxide (NO) in macrophage and production of reactive oxygen species (ROS) in lymphocyte that have important role in activation of immune response against Leishmania and elimination of parasite.Results showed that these compounds decrease the viability of the parasite and increase ROS and NO production in lymphocyte and macrophage respectively.These compounds can induce parasite killing, directly by decreasing the parasite viability and indirectly by exhibiting a significant increase on immune system.

Common variable immunodeficiency (CVID) and selective IgA deficiency (SIGAD) are the most common primary antibody deficiencies. These two diseases may have coincidence in one family and SIGAD can progress to CVID which suggest common underlying genetic defects between SIGAD and CVID. This study was designed to find the prevalence of multiple cases in families of Iranian patients with CVID or SIGAD.Serum samples were collected from all available first-degree relatives of 37 patients (23 patients with CVID and 14 with SIGAD) to check the levels of immunoglobulin and their subclasses and detect antibody deficiencies.First degree family members of 37 patients (106 individuals) were enrolled in this study. Thirty two percent of patients had multiple cases in their families. The frequency of primary antibody deficiency in the first relatives of the patients was estimated to be one per 9 family members. Most of the patients found among family members were siblings of the primary patients. Analysis in SIGAD family members showed that IgG and IgA levels in families with multiple cases were significantly lower than family members without multiple cases (p values of 0.048 and 0.021, respectively).Rate of families with multiple cases in Iran is more than the previous studies in other countries. This rate was not affected by the consanguinity of parents (p=0.081) or immunoglobulin level of the patients. Because of higher risk for the prevalence of these disorders in those with a positive family history of immunodeficiency, family screening programs in the patients with CVID and SIGAD can be suggested to be prioritized..

The results of many studies suggested possible relationship between polymorphism at codons 16 and 27 and development of tolerance to beta-2 adrenoceptor agonist responses as well as disease severity in asthmatic patients. This study was designed to evaluate the effect of polymorphism of beta2 adrenoceptors on response to salmeterol and fluticasone (as inhaled Seretide).Sixty-four patients with either mild or moderate-severe asthma were evaluated in this study. A four-week therapy with Seretide was conducted in moderate-severe asthmatics. The respiratory parameters and asthma score (based on GINA guidelines) were measured before and after run in period. Blood samples were genotyped at codons 16 and 27.No significant difference was observed in genotypes neither at codon 16 nor at codon 27 between mild and moderate-severe asthma groups. However, Patients in Arg/Arg (n = 8) category showed significant improvement in asthma control parameters and lung function compared with Arg/Gly genotype (n =20).These results suggest that genotyping may be useful in some asthmatic patients in order to better tailor asthma treatment plan.

Interleukin-13 (IL-13) is known to be a key regulator in immunoglobulin E (IgE) synthesis, mucus hypersecretion and airway hyperresponsiveness. Single nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations.This study was performed in 214 atopic patients (asthma n=108, allergic rhinitis n=106) and sex-matched healthy controls (n=120). Genotyping of IL-13 gene polymorphisms was performed using polymerase chain reaction-based restriction fragment length polymorphism method.A statistically significant association of the A-1512C polymorphism in IL13 gene was observed with atopy (p<0.001; χ2=19.0). Upon stratification of the data into asthma and AR association was revealed with both asthma (p=0.01; χ2=8.80) and AR (p<0.001; χ2=24.3) in Pakistani patients. Higher odds ratio (OR 95% CI) was observed for AR 3.42 (2.04-5.76) relative to asthma 2.40 (1.41-4.09) for the C allele compared to controls.In conclusion the study provides the evidence A-1512C polymorphisms in IL-13 is a risk factor for asthma and AR.

Leukotriene receptor antagonists(montelukast) have been used for many years in the treatment of asthma both acute and chronic stages. They are accepted commonly as safe but mostly possible side effects are ignored. However, montelukast also could lead to important adverse reactions like hallucinations. In literature only 2 reports have been found about hallucinations with it. One is a study which reports 3 patients from 48 children and the other is a 29 year-old case report. In our case, psychiatric adverse reactions of montelukast,especially hallucinations are reported similarly. We are presenting a child who had visual hallucinations after starting to use montekulast and after stopping the medicine these complaints disappeared in 48 hours. Although it is a safe drug, it should not be forgotten that it has psychiatric side effects which may be missed easily especially in children.

It is well known that desensitization treatment with aspirin can significantly improve symptoms and quality of life in patient with aspirin-exacerbated respiratory disease. However, its mechanism has not been clearly understood yet. In this case report, 41-year-old male patient was referred to our allergy and immunology department with complaints of chronic rhinosinusitis including postnasal discharge, sneezing, facial pain/pressure, waking up tired, nasal obstruction, smell loss for a long time. According to the patient, the complaints were controlled partially with nasal steroid and antihistamines, and single dose parenteral depot steroids were highly effective in controlling the symptoms and each time this effect lasted at least three weeks.The patient was told to use aspirin when needed analgesic and he started to use aspirin 500 mg bid. po for 10 days for his pain in the joints. The patient stressed the superiority of aspirin over other drugs including oral antihistamine and LTA and its equality to systemic steroid drugs in suppressing symptoms. It seemed that aspirin had positive effects in allergic inflammation at least in some subset of aspirin tolerant patients with chronic sinusitis.