Sensitization to common allergens among patients with allergies in major Iranian cities: a systematic review and meta-analysis / 한국역학회지

Various allergens are implicated in the pathogenesis of allergic diseases in different regions. This study attempted to identify the most common allergens among patients with allergies based on the results of skin prick tests in different parts of Iran. Relevant studies conducted from 2000 to 2016 were identified from the MEDLINE database. Six common groups of allergen types, including animal, cockroach, food, fungus, house dust mite, and pollen were considered. Subgroup analysis was performed to determine the prevalence of each type of allergen. The Egger test was used to assess publication bias. We included 44 studies in this meta-analysis. The overall prevalence of positive skin test results for at least one allergen was estimated to be 59% in patients with allergies in various parts of Iran. The number of patients was 11,646 (56% male and 44% female), with a mean age of 17.46±11.12 years. The most common allergen sources were pollen (47.0%), mites (35.2%), and food (15.3%). The prevalence of sensitization to food and cockroach allergens among children was greater than among adults. Pollen is the most common allergen sensitization in cities of Iran with a warm and dry climate; however, sensitization to house dust mites is predominant in northern and southern coastal areas of Iran.

Sensitization to common allergens among patients with allergies in major Iranian cities: a systematic review and meta-analysis / 한국역학회지

Various allergens are implicated in the pathogenesis of allergic diseases in different regions. This study attempted to identify the most common allergens among patients with allergies based on the results of skin prick tests in different parts of Iran. Relevant studies conducted from 2000 to 2016 were identified from the MEDLINE database. Six common groups of allergen types, including animal, cockroach, food, fungus, house dust mite, and pollen were considered. Subgroup analysis was performed to determine the prevalence of each type of allergen. The Egger test was used to assess publication bias. We included 44 studies in this meta-analysis. The overall prevalence of positive skin test results for at least one allergen was estimated to be 59% in patients with allergies in various parts of Iran. The number of patients was 11,646 (56% male and 44% female), with a mean age of 17.46±11.12 years. The most common allergen sources were pollen (47.0%), mites (35.2%), and food (15.3%). The prevalence of sensitization to food and cockroach allergens among children was greater than among adults. Pollen is the most common allergen sensitization in cities of Iran with a warm and dry climate; however, sensitization to house dust mites is predominant in northern and southern coastal areas of Iran.

Protective effect of edaravone against cyclosporine-induced chronic nephropathy through antioxidant and nitric oxide modulating pathways in rats

Background: Cyclosporine A [CsA] is an immunosuppressant with therapeutic indications in various immunological diseases; however, its use is associated with chronic nephropathy. Oxidative stress has a crucial role in CsA-induced nephrotoxicity. The present study evaluates the protective effect of edaravone on CsA-induced chronic nephropathy and investigates its antioxidant and nitric oxide modulating property

Methods: Male Sprague-Dawley rats [n=66] were distributed into nine groups, including a control [group 1] [n=7]. Eight groups received CsA [15 mg/kg] for 28 days while being treated. The groups were categorized as: - Group 2: Vehicle [n=10]. - Groups 3, 4, and 5: Edaravone [1, 5, and 10 mg/kg] [n=7 each]. - Group 6: Diphenyliodonium chloride, a specific endothelial nitric oxide synthase [eNOS] inhibitor [n=7]. - Group 7: Aminoguanidine, a specific inducible nitric oxide synthase [iNOS] inhibitor [n=7]. - Group 8: Edaravone [10 mg/kg] plus diphenyliodonium chloride [n=7]. - Group 9: Edaravone [10 mg/kg] plus aminoguanidine [n=7]. Blood urea nitrogen and serum creatinine levels, malondialdehyde, superoxide dismutase, and glutathione reductase enzyme activities were measured using standard kits. Renal histopathological evaluations and measurements of eNOS and iNOS gene expressions by RT-PCR were also performed. Data were analyzed using one-way analysis of variance [ANOVA] followed by Tukey's test [SPSS software version 18.0]

Results: Edaravone [10 mg/kg] significantly attenuated CsA-induced oxidative stress, renal dysfunction, and kidney tissue injury. Aminoguanidine improved the renoprotective effect of edaravone. Edaravone reduced the elevated mRNA level of iNOS, but could not alter the level of eNOS mRNA significantly

Conclusion: Edaravone protects against CsA-induced chronic nephropathy using antioxidant property and probably through inhibiting iNOS gene expression

Inhibition of NR2B-containing n-methyl-D-aspartate receptors [NMDARs] in experimental autoimmune encephalomyelitis, a model of multiple sclerosis

Neurodegeneration is the pathophysiological basis for permanent neurological disabilities in multiple sclerosis [MS]; thus neuroprotection is emerging as a therapeutic approach in MS research. Modulation of excitotoxicity by inhibition of NMDARs has been suggested for neuroprotection. but selective antagonisation of the NR2B subtype of these receptors, a subtype believed to play a more pivotal role in neurodegeneration, has not been tested in MS. In this study inhibition of NR2B-containing NMDAR was evaluated on the animal model of MS, experimental autoimmune encephalomyelitis [EAE]. EAE induction was done using MOG in C57BL/6 mice. Therapeutic administration of different doses of highly selective NR2B-containing NMDAR inhibitor [RO25-6981] was compared with memantine [non-selective NMDAR antagonist] and vehicle. Neurological deficits in EAE animals were more efficiently decreased by selective inhibition of NR2B-containing NMDARs. Histological studies of the spinal cords also showed decreased inflammation, myelin degradation and neuro-axonal degeneration when RO25-6981was administered with higher doses. The effects were dose dependent. Regarding the role of NR2B-containing NMDARs in excitotoxicity, selective inhibition of these receptor subtypes seems to modulate the neurological disabilities and pathological changes in EAE. Further elucidation of the exact mechanism of action as well as more experimental studies can suggest NR2B-containing NMDAR inhibition as a potentially effective treatment strategy for slowing down the clinical deterioration of disability in MS

Clinical and genetic features in patients with cystic fibrosis in southwestern Iran

Cystic fibrosis [CF] is a common autosomal recessive genetic disease caused by a mutation in the CF transmembrane conductance regulatory [CFTR] gene. This study attempted to identify the most common CFTR mutations and any correlations between certain mutations and the clinical presentation of the disease in CF patients in southwestern Iran. Twenty nine common CFTR gene mutations were examined in 45 CF patients. Chronic cough, intestinal obstruction, dehydration, heat exhaustion and steatorrhea were the most common early clinical symptoms among our patients. The most common mutation was deltaF508, with an allele frequency of 21%. The homozygous deltaF508 mutation was observed in eight patients [18%], and three patients [7%] were deltaF508 carriers. The 2183AA>G mutation was observed in four patients, one of whom was also a deltaF508 carrier. The R1162X mutation was detected in two patients. The G542X, R334W and N1303K mutations were detected each in one patient, the first of whom was also a deltaF508 carrier. Out of 45 patients, 27 [60%] had none of the CFTR gene mutations we tested for. The most frequent mutations in southwestern Iranian patients with CF should be identified by sequencing the entire CFTR gene in order to optimize the design of a diagnostic kit for common regional mutations

Serotonin transporter gene polymorphisms in southwestern Iranian patients with irritable bowel syndrome

Irritable bowel syndrome is a common chronic functional gastrointestinal disorder of unknown etiology. Serotonin is an important factor in sensory signaling in the brain-gut axis, which plays a key role in intestinal motility and secretion. Serotonin clearance is mediated by a specific protein called the serotonin reuptake transporter. Transcription activity of the serotonin transporter gene is affected by some polymorphisms in this gene. The aim of this study was to investigate the relationship between serotonin transporter gene polymorphisms and irritable bowel syndrome. The 5-HTTLPR, rs25531 and STin2VNTR polymorphisms of the serotonin transporter gene were analyzed by PCR-based methods in 50 patients with irritable bowel syndrome and 100 healthy controls. Serotonin transporter polymorphisms were similar in patients and healthy controls. There were no significant differences in allele or genotype frequencies between the two groups. Our findings suggest that polymorphisms in the gene encoding for the serotonin transporter are not associated with irritable bowel syndrome. Interactions between environmental factors and predisposing genetic factors are important in the pathophysiology of irritable bowel syndrome, and further genetic and epigenetic research may provide novel insights into the mechanisms contributing to this disease

Effect of thermal stress on MICA/B induction in a human liposarcoma cell line

A possible mechanism by which hyperthermia enhances tumor immunogenicity is the induction of NKG2D ligands on tumor cells. Although the expression of MHC class I chain-related protein A and B [MICA/B] has previously been reported in different carcinomas, there is no information about MICA/B expression in liposarcomas. To investigate MICA/B induction in a human liposarcoma cell line [SW-872] after thermotherapy. SW-872 and HeLa cell lines were subjected to thermal stress for 1 h at 42, 44 and 46[degree sign]C, and after 2, 4 and 6 h of incubation at 37[degree sign]C, MICA/B expression was assessed at the mRNA and protein levels. Despite high levels of MICA/B transcripts in SW-872 cells at baseline, the expression of these genes decreased significantly at both the mRNA and protein levels after almost all thermal treatments. Our data conclude that thermotherapy under 42-46[degree sign]C had no effect on MICA/B induction on SW-872 liposarcoma cell line but the effects of fever-range temperatures remain to be tested on this cell line

Hyperthermia increases natural killer cell cytotoxicity against SW-872 liposarcoma cell line

Although there is convincing data in support of the effectiveness of hyperthermia in tumor therapy, the molecular mechanisms underlying the clinical effects of hyperthermia are still poorly understood. To investigate natural killer [NK] cell cytotoxicity against heat-treated SW-872 and HeLa tumor cell lines. NKG2D ligands and HLA class I transcription were examined using quantitative real-time PCR in treated tumor cell lines at 0, 2, 4, 6 and 12 h following thermal treatment at 39 Degree °C and 42 Degree °C for 1 h. The expression of MICA/B, ULBP1 and ULBP2 were also determined by flow cytometry. NK92-MI cytotoxic activity against heat-treated target cell lines was assessed by LDH release as well as annexin-V and 7-AAD assays. Our results showed that heat treatment at 39°C improved the cytolytic activity of NK cells against SW-872 cells without increasing NKG2D ligand concentration or decreasing HLA class I levels. The observed increase in the cytotoxicity of NK cells against SW-872 cells after hyperthermia does not coincide with changes in MICA/B, ULBP1 and ULBP2 ligands of NKG2, however, the expression of other ligands in target cells may have made the cells susceptible to the cytotoxic effect of NK cells

Specific IgE to common food allergens in children with atopic dermatitis

Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow's milk, hen's egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow's milk [31%], hen's egg [17.7%], tree nuts [17.7%], wheat [12.2%], potato [11.1%], tomato [8.8%] and peanut [8.8%]. In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. Our results showed that cow's milk, hen's egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients

Factor V G1691A and prothrombin G20210A gene polymorphisms among Iranian patients with cerebral venous thrombosis

Objective: Cerebral venous thrombosis (CVT) is an important cause of stroke, especially in young adults, that has many predisposing factors. G20210A mutation in prothrombin gene (Factor II) and G1691A mutation in Factor V Leiden (FVL) are two common hereditary causes of CVT. This study aimed to study the rate of these mutations in patients with CVT from Fars Province in southern Iran. Methods: In a case-control study, 57 case patients with defi nite diagnosis of CVT, confi rmed clinically and by MRI and MRV, and 50 sex and age matched healthy controls, with no family history of thrombosis, were enrolled from March 2008 to March 2010. G1691A mutation of FVL and G20210A mutation of factor II were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Mutation in G20210A of factor II was found in 3.6% of patients and 4% of the controls (P=1). For FVL mutation, 7% of the patients carried the mutant allele while this mutation was not found in the controls (P=0.12). Two and 4 patients were heterozygous for prothrombin G20210A and FVL G1691A mutations, respectively. Conclusions: It seems that G20210A mutation in Factor II and G1691A mutation in FVL are not responsible for CVT in the southern Iran population with predominant Fars ethnicity.

Association of HLA-DQA1*0101/2 and DQB1*0502 with myasthenia gravis in Southern Iranian patients

Myasthenia gravis is an autoimmune disorder of neuromuscular junction characterized by skeletal muscle weakness and fatigability. Different genes may control the induction and clinical presentation of this disease. Various HLA alleles are reported as predisposing or protective genetic elements in myasthenia gravis The aim of this study was to investigate the probable association between HLA-DQ alleles and myasthenia gravis in southern Iranian patients. HLA-DQA1 and DQB1 alleles were determined in 104 sporadic patients with myasthenia gravis using polymerase chain reaction - restriction fragment length polymorphism method and the results were compared to 816 healthy controls. HLA-DQA1*0101/2 [39.4%] and DQB1*0502 [21.6%] were the most frequent alleles in southern Iranian patients with myasthenia gravis. These alleles revealed positive associations with the disease with relative risks of 1.69 and 2.41, respectively. The most common haplotype was DQA1*0101/2-DQB1*0502 in these patients. According to the results of this study, DQA1*0101/2 and DQB1*0502 alleles might be considered as predisposing genetic factors to myasthenia gravis while DQA1*0501, DQB1*0301 and *0602/3 show protective roles against this disease

Analysis of human leukocyte antigen class II gene polymorphism in Iranian patients with Papillon-Lefevre syndrome: a family study

Papillon-Lefevre syndrome [PLS] is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early development of aggressive periodontitis. Although cathepsin C [CTSC] gene mutations have been established in about 70-80% of PLS patients, it is assumed that the patients may have dysfunctioning of immune defense mechanisms. To assess the association of HLA class II genes and PLS. HLA class II genes were typed in nine Iranian PLS patients and their family members and the results were compared to 816 Iranian healthy subjects. The results of this study revealed that DRB1*0101 and DRB1*0301 alleles were more frequent in PLS patients than in normal controls. However, there was no significant difference between PLS patients and normal controls. Moreover, the same haplotypes and genotype combinations were also observed in some patients and their healthy siblings. The results of this study showed no strong association between HLA class II alleles and PLS

Antigen-specific antibody response in juvenile-onset SLE patients following routine immunization with tetanus toxoid

Infection is now the most common cause of morbidity in Systemic Lupus Erythematosus [SLE]. There is lack of information regarding the specific antibody formation in response to vaccines in young SLE patients. To determine the efficacy of anti-tetanus antibody response in young patients with SLE. Forty SLE patients with mean age of 14.1 years [range: 7-21] and 60 age and sex matched normal controls were enrolled in this study over a period of one year. Diagnosis was made according to the ACR criteria and disease activity was determined based on SLE Disease Activity Index [SLEDAI]. All patients and controls had received the complete schedule of tetanus vaccinations consisting of three primary doses and two boosters by the age of six. Serum immunoglobulins and anti-tetanus antibody titers were determined by Nephelometry and ELISA. Anti-tetanus antibody levels greater than 0.1 IU/ml have been suggested as protective. In all of the patients and controls anti-tetanus antibody titer was > 0.1 IU/ml. IgG, IgA, and IgM levels were in the normal range for their age. Mean disease activity score was 4.9 [range: 0-16]. There was no association between SLEDAI score and anti-tetanus antibody response. School age onset and immunosuppressive therapy does not seem to interfere with development of consistent immunity to tetanus vaccine in young SLE patients

HLA class I gene polymorphism in Iranian patients with papillon-lefevre syndrome

Papillon-Lefevre Syndrome [PLS] is a rare autosomal recessive disorder characterized by diffused palmoplantar keratoderma and severe periodontitis. Increased susceptibility to infections due to impairment of the immune system is considered to be involved in pathoetiology of this disease. According to the crucial function of HLA molecules in immune responses and association between certain HLA class I alleles and some periodontal or skin diseases, this study was designed to evaluate the relation of HLA class I genes and PLS. HLA class I genes were typed by PCR-SSP [Polymerase Chain Reaction with Sequence Specific Primers] method in eight Iranian PLS patients and 89 healthy controls. The results showed no significant difference between the patients and controls. Moreover, identical haplotypes or genotypes were also observed among PLS patients and their healthy siblings. It seems that further genes are involved in genetic susceptibility to PLS. However the results of this study showed no significant association between HLA class I genes and PLS, molecular analyses of killer immunoglobulin-like receptors [KIRs] and MHC class I chain-related gene A and B [MICA/B] in PLS may clear many obscure points about the genetic factors involved in these diseases

HLA class II genetic diversity in Arabs and Jews of Iran

Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. This study was designed to investigate the genetic relationship of Iranian Arabs and Jews using HLA-class II genetic diversity. HLA-DRBl, DQAl, and DQB1 allele frequencies and haplotypes were determined in 134 Iranian Arabs from two different communities and 91 Iranian Jews using PCR/RFLP and PCR/SSP methods. Neighbor-joining analyses showed a closer genetic relationship between Iranian Arabs and Iranian Jews than between either Iranian Arabs and Middle Eastern Arabs or Iranian Jews and other Jews. The results of AMOVA test also revealed no significant difference between these populations and other Iranians. It seems that, Iranian Arabs are originally from the Iranian gene pool and speak Arabic due to their encounter with Arabs. Iranian gene flow to immigrant Jews followed by their expansion in this country may also explain the close genetic relationship among different Iranian ethnic groups

Iranian Lurs genetic diversity: an anthropological view based on HLA class II profiles

HLA genes are highly polymorphic and certain alleles are frequent only in specific populations. Therefore, HLA is a unique tool for studying the genetic relationship between different populations. Iranians are ethnically diverse people and one of the major ethnic groups in Iran is Lur population inhabiting along the central and southern parts of Zagros Chain Mountain. Genetic relationship among three Lur subpopulations was investigated based on HLA class II profiles. HLA typing was performed using PCR/RFLP and PCR/SSP methods in 154 individuals from three Lur subpopulation living in Luristan, Kohkiloyeh/ Boyerahmad, and Chahar-Mahal/ Bakhtiari. The most common DRB1 allele in Lurs of Luristan and Kohkiloyeh/ Boyerahmad was *1103=4 while DRB1*0701 was the most common allele in Bakhtiaris. DQA1*0501 and DQB1*0301 were the most frequent alleles and DRB1*1103=04-DQA1*0501-DQB1*0301 was the predominant haplotype in the three studied subpopulations. Neighbor-joining tree based on Nei's genetic distances and correspondence analysis according to DRB1, DQA1, and DQB1 allele frequencies showed a close genetic relationship between Lurs of Luristan and Lurs of Kohkiloye/ Boyerahmad and they were well separated from Bakhtiaris. The results of AMOVA revealed no significant difference between the three studied groups of Lurs and other major ethnic groups of Iran. The results of this study revealed that Bakhtiaris were genetically far from the two other Lur subpopulations. Despite a probable common ancestor, this genetic difference might be explained by Bakhtiaris admixture with other Zagros inhabitants due to their nomadic life style