Iranian Journal of Allergy, Asthma and Immunology
Volume:20 Issue: 3, Jun 2021

This letter to the editor has not an abstract.

Allergic rhinitis (AR) is a prevalent disease affecting the quality of life of patients throughout the world. This study aimed to assess the prevalence of AR and its association with chronic rhinosinusitis (CRS) in the adult population living in Bushehr, southwestern part of Iran. In this population-based study, a total of 5420  individuals aged 15-65 years were selected through a multi-stage, cluster, random sampling method from which 5201 of them completed the Global Allergy and Asthma Network of Excellence (GA2LEN) questionnaire (Response rate=96.1%). The prevalence of AR, based on Allergic Rhinitis and Its Impact on Asthma (ARIA) classification (mild or moderate; intermittent or persistent) was calculated and the association of AR and CRS was evaluated using a multiple logistic regression model. The overall prevalence of AR was 28.8%, and for the intermittent and persistent AR were 25.9% (out of which 81.34% were moderate to severe) and 74.1% respectively. Moreover, the prevalence of AR was significantly higher in health workers and smokers (p=0.002 and p<0.001, respectively). Furthermore, an association was found between AR and CRS (p<0.001, aOR: 4.68, 95%CI: 4.07-5.39), and also, between the persistent AR and CRS as compared with the intermittent (p<0.001, aOR: 4.21, 95%CI: 3.40-5.22). The present study showed that the prevalence of AR in Bushehr (Southwestern part of Iran) was significantly high. In addition, the results indicated a strong association between AR and CRS, especially in individuals with moderate to severe persistent AR.

Allergic rhinitis and eczema are two common global diseases that can lead to impaired quality of life. Determining the prevalence of these allergic disorders can be useful in planning prevention and treatment. This study aimed to investigate the prevalence and severity of allergic rhinitis and eczema in adolescents living in Yazd city. Using an electronic questionnaire based on the Global Asthma Network (GAN) core questionnaire, 5141 adolescents aged 13–14 years were cross-sectionally surveyed. The prevalence of current symptoms of rhinitis turned out to be 36.3%, proving significantly higher in boys (p=0.009). Moreover, the prevalence of allergic rhinitis and rhinoconjunctivitis in the past year leveled at 12.4% and 10.5%, respectively; however, the former was significantly higher in females (p=0.014). Additionally, severe rhinoconjunctivitis was observed in 0.2% of the participants with no gender preference (p=0.09). Confirmed hay fever by a doctor was reported in 13.2% of adolescents, significantly higher in males (p<0.001). The prevalence of current itchy rash and current eczema was found to be 5.5%, and 2.9%, respectively, with no difference in terms of gender. Severe atopic eczema and eczema confirmed by a doctor were seen in 0.4% and 5% of the participants, no gender preference was identified. Concurrent prevalence of current rhinoconjunctivitis and eczema was detected in 1% of the participants. Despite the increasing trend of allergic diseases in most parts of the world, the prevalence of rhinoconjunctivitis and eczema in adolescents has not increased in Yazd in the last two decades, and this city is located in a low to moderate prevalence area.

As asthma and atherosclerosis have similar pathophysiological mechanisms and risk factors, asthmatic patients may have an increased risk of atherosclerosis. This study aimed to determine the possibility of a higher risk of atherosclerosis in asthma patients compared with healthy controls by measuring carotid elasticity and distensibility. This was a cross-sectional study on 326 participants including 221 patients (129 [58.37%] females) with persistent asthma, aged 46.47±11.58 years, body mass index (BMI) of 29.74±3.99, and 105 healthy control subjects (60 [57.14%] females) aged 46.08±11.35 years, and BMI of 29.42±3.76. Of the 221 patients with asthma, 75 (33.93%) had mild, 74 (33.48%) had moderate and 72 (32.57%) had severe asthma. The carotid distensibility and elasticity were recorded and compared in both patients and control groups. There was no statistically significant difference between the patients and healthy control groups in terms of age, BMI and gender (p=0.775, p=0.482, and p=0.834, respectively). A statistically significant difference was determined between the patient and control groups in respect of both distensibility and elasticity (10.93±1.64 vs. 11.5±1.31, p=0.002 and 0.21±0.03 vs. 0.22±0.04, p=0.001, respectively). Statistically significant differences were determined between the control group and the asthma subgroups in respect of distensibility and elasticity (p<0.001, for both comparisons). The results showed that the difference was mainly due to the patients with severe asthma. Carotid distensibility and elasticity were decreased in asthmatic patients, and the main reason for this decrease was the patients in the severe asthma group. These results may suggest that the risk of subclinical carotid atherosclerosis is increased in patients with asthma, especially those with severe asthma

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.

Airborne pollen is considered one of the causative agents of hay fever, allergic rhinitis, conjunctivitis, and asthma. We aimed to investigate airborne pollens in the context of Shiraz located in the southwest of Iran and find their association with meteorological parameters.  The survey was conducted from October 2017 to September 2018, using seven days of volumetric Burkard spore trap, located in the center of the city. A total of 5810 pollen grains/m3 belonging to 15 taxa were identified and recorded. Among them, 73.8% was the tree, while the grass, shrub, and weed constituted 13.56%, 3.5%, and 9.2% of total reported pollens, respectively. The major pollen types were Platanaceae (28.39%), Oleaceae (21.17%), Pinaceae (15.11%), Amaranthaceae (9.29%), and Brassicaceae (8.02%). A higher number of pollen counts and types were recorded in March, followed by September, while it was lower in May. Meteorological parameters were correlated with the monthly pollen counts. Wind speed was found to have a positive correlation with Platanaceae concentration. The significant correlation between pollen concentration and the temperature was positive for Poaceae, Amaranthaceae, and Plantaginaceae and negative for Rosaceae, Oleaceae, and Ulmaceae.  Poaceae and Amaranthaceae were negatively correlated with humidity and positively with Rosaceae, Oleaceae, and Plantaginaceae. A negative correlation was found between rainfall and Poaceae and Amaranthaceae, while Plantaginaceae had a positive correlation with this parameter. The results of this study may be helpful for allergologists in the diagnosis and treatment of airborne allergic disorders due to pollen grains.

MicroRNA-124 (miR-124) is known as an important regulator of the immune system and inflammatory response. Studies have reported that this miRNA is dysregulated in autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A functional analysis demonstrated that rs531564 (C>G) affects the biogenesis of primary microRNA transcript-124 (pri-miR-124) and changes the expression of mature miR-124. In the present study, for the first time, we intended to evaluate the possible association between rs531564 polymorphism with SLE and RA risk.  In this case-control study, 110 patients with SLE, 115 patients with RA, and 120 healthy subjects were enrolled to evaluate rs531564 genotypes with real-time polymerase chain reaction (PCR) high resolution melting method. Our findings demonstrated that frequency of GC genotype and G allele were considerably higher in the control group than RA patients, demonstrating that that GC genotype and G allele have a protective effect for healthy individuals (GC vs CC; OR: 0.29; 95%CI [0.12,0.67] and G vs C; OR: 0.42; 95%CI [0.23,0.78]). However, no significant correlation was confirmed between allele and genotype frequencies of rs531564 with SLE risk (p>0.05). However, the G allele in rs531564 polymorphism was associated with serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-dsDNA antibody, C3, C4, and creatinine, and frequency of renal involvements in SLE patients (p<0.05). Moreover, in RA patients, the G was correlated with lower concentration ESR and CRP (p<0.001).  Our findings propose a considerable association between rs531564 polymorphism in the pri-miR-124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.

Perturbed expression of microRNAs (miRs) has been reported in different diseases including autoimmune and chronic inflammatory disorders. In this study, we investigated the expression of miR-25-3p and its targets in the central nervous system (CNS) tissue from mice with experimental autoimmune encephalomyelitis (EAE). We also analyzed the expression of miR-25 and its targets in activated macrophages and splenocytes. EAE was induced in 12-week old female C57BL/6 mice; using myelin oligodendrocyte glycoprotein 35-55/complete Freund's adjuvant (MOG35-55/CFA) protocol. The expression of miR-25-3p and its targets, as well as the expression of inflammatory cytokines, were analyzed. We next established primary macrophage cultures as well as splenocyte cultures and evaluated the levels of miR-25-3p and its target genes in these cells following activation with lipopolysaccharide (LPS) and anti-CD3/anti-CD28 antibodies, respectively. MiR-25-3p expression showed a strong positive correlation with the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1α, and IL-6 pro-inflammatory cytokines. The expression of phosphatase and tensin homolog (Pten) and Krüppel-like factor 4 (Klf4) was significantly reduced at the peak of the disease. Interestingly, Pten and Klf4 expression showed a significant negative correlation with miR-25-3p. Analysis of miR-25-3p expression in LPS-treated primary macrophages revealed significant upregulation in cells treated with 100ng/ml of LPS. This was associated with suppressed levels of miR-25-3p targets in these cells. However, anti-CD3/anti-CD28-stimulated splenocytes failed to show any alterations in miR-25-3p expression compared with vehicle-treated cells. Our results indicate that miR-25-3p expression is likely induced by inflammatory mediators during autoimmune neuroinflammation. This upregulation is associated with decreased levels of Pten and Klf4, genes with known roles in cell cycle regulation and inflammation.

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients. This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit. The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p<0.05). ROC curve analysis showed that miR-146a-5p (AUC=0.8, sensitivity= 96%, specificity=86%), miR-24-3p (AUC=0.7, Sensitivity=95%, Specificity=75%) and miR-125a-5p (AUC=0.71, sensitivity=93%, specificity=84%) could be used as suitable biomarkers for RA diagnosis. Increased expressions of miR-146a-5p, miR-24-3p, and miR-125a-5p in RA patients indicate that the miRNAs are involved in disease incidence and progression, and the measurement of their expression can play an essential role in the diagnosis and treatment of the disease.

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.

Human platelet antigens (HPAs) are glycoproteins on the platelet surface that a single nucleotide mutation in the coding region gene could lead to the variation of different HPA polymorphisms. These antigens have shown variation among different races and may trigger immune responses during blood transfusion and pregnancy. Genotyping of HPAs is useful for managing these reactions and establishing a platelet registry to decrease platelet transfusion reactions. This study aimed to compare allelic and genotype frequencies of human platelet antigens in the Azeri ethnicity by TaqMan Real-time and polymerase chain reaction with sequence-specific primers (PCR-SSP) methods. DNA was extracted from the whole blood of 100 Azeri blood donors in the Ardabil Blood Transfusion Center. Genotyping of HPA-1 to -5 and -15 was performed by TaqMan Real-time PCR, and PCR-SSP and consistency of results were evaluated. The results of PCR-SSP and TaqMan Real-time PCR showed complete consistency. The allele frequencies were 91.5% and 8.5% for HPA-1a and -1b; 88% and 12% for HPA-2a and -2b; 58% and 42 % for HPA-3a and -3b; 100% for HPA-4a; 91% and 9% for HPA-5a and -5b; 56.5% and 43.5% for HPA-15a and -15b alleles. Not incompatibility was detected in HPAs genotyping by PCR-SSP and TaqMan Real-time PCR so that real-time PCR can be used as a robust and quick method for HPA genotyping. We found differences between Azeri blood donors and previously reported HPAs alleles’ frequency in other ethnicities in the country. This fact highlights the need for a platelet registry to recruit platelet donors from different ethnicities and increase the number of donors by using faster methods.

T-lymphocytes have critical functions in the immune responses against viral and intracellular bacterial infections as well as cancers. Antigen (Ag)-specific T-lymphocyte clones enriched and expanded in vitro are valuable tools in the study of immune responses in animal models and adoptive T-cell therapy of patients with cancer or infection. We described a method for inducing, enriching, and replicating Ag-specific poly-clonal T-cells from BALB/c mice infected with live Bacillus Calmette Guérin (BCG) bacterium. During a 7-8 days procedure, T-lymphocytes were purified from immune cells of lymph nodes stimulated with immunodominant Ag of BCG, TB10.4, and expanded by interleukin -2 cytokine. We evaluated the effect of Ag doses (1, 10, and 100 μg/mL) and exposure method of Ag presenting cells (APCs) to T-cells, on T-cells’ proliferation, viability, and Interferon-gamma (IFN-γ) secretion at 2, 5, and 7 days after Ag stimulation. Increasing Ag concentration increased the average cell division, but at the highest dose of Ag (100 μg/mL), T-cell viability is decreased. Only clones induced by 10 μg/mL Ag produced a desirable amount of IFN-γ. Incubation of Ag and APCs, 24 h before T-lymphocytes addition, increased the proliferation and viability of cells. T cells are in a more favorable condition around day 5 of Ag stimulation in terms of proliferation and survival, and it is the desired time for T cell restimulation. For optimal preparation of specific T-cells for adoptive cell transfer, optimization of Ag dose, the order of APCs and T-cells exposure with Ag, and the duration of initial Ag stimulation, as well as the time for restimulation, is essential.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of genetic disorders characterized by infections with weakly virulent environmental mycobacteria (EM) or Mycobacterium bovis bacillus Calmette-Guérin (BCG). Herein, we described the case of a 4.5-year-old boy with protein-losing enteropathy, lymphoproliferation, and candidiasis, who was found to have disseminated Mycobacterium simiae infection. A homozygous mutation in the IL12B gene, c.527_528delCT (p.S176Cfs*12) was identified, responsible for the complete IL-12p40 deficiency. He was resistant to anti-mycobacterial treatment and finally died due to sepsis-related complications.