Iranian Journal of Allergy, Asthma and Immunology
Volume:20 Issue: 1, Feb 2021

Previous studies have reported that T cell immunoglobulin domain and mucin domain-3 (TIM-3) 574T>G and 1516G>T are associated with the risk of asthma. However, the results are inconsistent due to the small sample size and varied age in studies. We performed this meta-analysis to systematically evaluated the effect of TIM-3 574T>G and 1516G>T genetic polymorphisms on asthma. Eligible articles that reported an association between TIM-3 574T>G and 1516G>T genetic polymorphisms and asthma were searched in PubMed, Medline, EMBASE, Google Scholar, and China National Knowledge Infrastructure up to April 2020. Random or fixed-effects models were used to calculate the summary of odds ratios (ORs) and 95% confidence intervals (CIs) to detect any potential associations between TIM-3 genetic polymorphisms and asthma. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Publication bias was analyzed using the Egger test.A total of 11 case-control studies including 2077 asthma patients and 2122 control subjects were finally analyzed (published data form 2004-2018). The pooled results indicated that TIM-3 574T>G genetic polymorphisms were significantly associated with an increased risk of asthma under the dominant model (GG vs. GT +TT: ORs=2.26, 95% CI 1.09-4.69) and allele model (G vs T: ORs=2.60, 95% CI 1.20-5.64). However, no significant associations between TIM-3 1516G>T genetic polymorphisms with asthma in any model was found. No evidence of publication bias was observed. Our study indicates that TIM-3 574T>G genetic polymorphisms were associated with increased risk of asthma and the TIM-3 1516G>T genetic polymorphisms may not be correlated with asthma.

The Coronavirus disease 2019 (COVID-19) virus spread from Wuhan, China, in 2019 and is spreading rapidly around the world. COVID-19 victims are almost associated with cardiovascular disease, high blood pressure, diabetes, and other underlying diseases. Concerning the high prevalence of these disorders, widespread mortality threatens global society, and its fatality rate may increase with increasing COVID-19 prevalence in countries with older populations. Therefore, evaluating patients' clinical status with severe COVID-19 infection and their medical history can help manage treatment. Currently, one of the considered treatments is angiotensin-converting enzyme 2 (ACE2) inhibition. This study investigated virus entry mechanisms through membrane receptors, their role in the pathogenesis of COVID-19 and underlying diseases, and treatment methods based on the viral entrance inhibition. According to existing studies, inhibition of ACE2 can increase oxidative stress, inflammation, fibrosis and ultimately exacerbate underlying diseases such as cardiovascular disease, kidney disease, diabetes, and hypertension in individuals with COVID-19. The ACE2 inhibition is not suitable for patients with COVID-19 with underlying diseases, but it seems that the recombinant ACE2 solution is more appropriate for inhibiting the virus in these patients if hypotension would be monitored.

Asthma, as the most common chronic disease in children, encompasses substantial health and socioeconomic burden worldwide. This study aimed to evaluate the prevalence, severity, and management of asthma in adolescents aged 1314 years. This crosssectional study, which was part of the Global Asthma Network (GAN) 2020 survey, was conducted in early 2020 in Yazd, Iran. A total of 48 schools in Yazd city were selected by cluster sampling. In this study, 5141 students, including 3069 (59.7%) females and 2072 (40.3%) males participated. Prevalence of ever and current wheezing was 19% and 9% respectively. The former was significantly higher in males than females (p<0.001). About 2% of the participants, which was 22.1% of students with current wheezing, had severe asthma. The prevalence of severe asthma was significantly higher in males (p=0.026). Our results showed that 4.8% of students had confirmed asthma by a doctor, significantly predominant in males (p<0.001). The prevalence of using inhaled medicines in the past 12 months was 3.8%, which was significantly higher in males than females (p<0.001). The prevalence of using shortacting βagonists (SABA) and longacting βagonists (LABA) was 2.3% and 1.4% among the students, respectively, with a male predominance (p=0.019). About 1.2% and 0.8% of participants were using inhaled corticosteroids (ICS) and the combination of ICS and LABA, respectively, which was significantly higher in male participants (p<0.001). According to our findings and in comparison to the previous ISAAC study in Yazd, the prevalence of severe asthma has decreased which indicates better management of asthma during the past two decades.

The elevated neutrophiltolymphocyte ratio (NLR) is associated with poor clinical outcomes, especially in proinflammatory states such as surgical injuries and severe hemorrhages. Therefore, it was hypothesized whether NLR value at the time of admission could be a prognostic indicator of hospital mortality in trauma patients. This retrospective cohort study was conducted on 865 trauma patients referred to Rajaee Hospital between April 2016 and July 2019. The NLR value was calculated at the time of admission, and receiver operating characteristics (ROC) curve analysis was used to determine the cutoff point value of admission NLR related to hospital mortality of trauma patients. Furthermore, KaplanMeier survival analysis and Cox regression models have been applied to determine the effectiveness and prognostic potential of the admission NLR in the hospital mortality of trauma patients. The median age of the trauma patients was 32 years with an interquartile range (IQR) of 23 to 48 years, and most of them were male (83.9%). Also, trauma patients had a median injury severity score (ISS) of 9 (IQR=416) and a median Glasgow coma scale (GCS) of 14 (IQR=915). The cutoff value for admission NLR was 5.27 (area under the curve: 0.642, 95%CI: 0.5590.726, p=0.001). In KaplanMeier survival analysis, the admission NLR>5.27 was an indicator of hospital mortality in trauma patients (p=0.001). Multivariate Cox regression models demonstrated that trauma patients with an admission NLR>5.27 hada 2.33fold risk of hospital mortality (hazard ratio=2.33, 95%CI: 1.025.38, p=0.041). Furthermore, the admission NLR>5.27 was associated with a higher risk of hospital mortality in trauma patients with age≥65 years, systolic blood pressure≤90 mmHg, blood potassium>4.5 mmol/L, blood sodium>144 mEq/L, blood potential hydrogen (pH)≤7.28, GCS≤8, ISS>24 and blood base excess≤6.1 mEq/L.The NLR value greater than 5.27 at the time of admission was associated with poorer outcomes, and it can be considered an independent prognostic indicator of hospital mortality in trauma patients.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients. We observed the positive associations of DRB1*07 and DRB1*07-DQB1*02 haplotypes with articular and pulmonary involvement (p=0.006 and p<0.001 respectively), DRB1*03 andDQB1*02 alleles, and DRB1*03-DQB1*02 haplotypes with cutaneous (p=0.03, p=0.004 and p=0.02 respectively) and renal involvement, and DRB1*13 as well as DRB1*13-DQB1*06haplotypes with renal involvement. Conversely, negative associations of DRB1*13 with cutaneous and gastrointestinal disorders (p=0.004 and p=0.02 respectively) and DRB1*01 with renal involvement (p=0.03) were found in our patients. Patients carrying susceptible HLA-DRB1alleles had a higher risk for expression of cutaneous involvement (p=0.03), anti-coagulant antibody development (p=0.01), and a lower risk for pulmonary disorders compared to patients' negatives for susceptible alleles (p=0.04). Our findings on associations between HLA risk allele (DRB1*03) as well as non-risk alleles with particular clinical manifestations and between the potentially protective allele (DRB1*01) and protection against renal involvement indicate the important role of HLAclass II genes in predisposing of specific serological and clinical features of SLE disease which could be implicative for therapeutic applications and better management of SLE patients.

Crab allergy is reported as a serious form of food allergy in many countries. This study was aimed to identify the major allergens of the local mud crab, Scylla tranquebarica (S. tranquebarica), and subsequently, determine the effect of vinegar treatments on the crab allergens. Crab muscles were treated with synthetic and natural vinegar. Crab proteins were then extracted from the untreated and vinegar-treated crabs. All extracts were then fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and analyzed by immunoblotting; using sera from crab-allergic patients. The crab proteins were then further fractionated by two-dimensional electrophoresis (2-DE) and analyzed by mass spectrometry (MS). The untreated crab had 38 protein bands, while that was only a few bands between 18 to 73 kDa for the vinegar-treated crabs. Immunoblotting of untreated crab revealed 20 IgE-binding bands, whereas the vinegar-treated crabs could only retain a few IgE-binding bands. Five major allergens were identified with molecular weightsof38, 42, 49, 63, and 73 kDa in the untreated crab. In contrast, the vinegar-treated crabs had only a few major allergens with molecular weights of 38, 42, and 73 kDa. MS identified the 43 and 49 kDa as arginine kinase, while the 38, 63, and 73 kDa were identified as tropomyosin, actin, and hemocyanin, respectively. In conclusion, we found three common major allergens for S. tranquebarica including tropomyosin, arginine kinase, and actin, and one novel allergen known as hemocyanin. All the major allergens could retain minimal allergenic capability in vinegar-treated crabs, suggesting that vinegar treatments might be useful to reduce crab allergenicity. These data would assist the clinicians in the management of crab-allergic patients worldwide.

Ischemia/reperfusion (I/R) injury in cadaveric liver transplantation is not avoidable. Liver I/R injury is an important phenomenon in hepatic damage. MicroRNA-21 (miR-21) plays an important role in I/R injury. The present study aimed to determine the expression pattern of miR-21 in liver I/R injury/recovery and its correlation with the immunologic transmission signals pathways in several days post-reperfusion.In an animal model for I/R in the liver, 40 male Balb/c mice were divided into 3 groups. The animals were monitored for 3 and 24 hours, and also for 4, 7, 14, and 28 days post-reperfusion. Liver tissue damage was assessed by histopathology. The plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC) levels were measured with enzymatic assays. MiR-21, programmed cell death 4 (PDCD4) mRNA, T-cell-restricted intracellular antigen 1 (TIA1) mRNA, and fas ligand (FASL) mRNA expression levels were measured; using reverse transcription-polymerase chain reaction (RT-PCR) at different times after the reperfusion in liver tissue and blood. Histopathology and plasma ALT, AST, ALP, and TAC levels confirmed liver damage induced by I/R injury. MiR-21 increased by twofold in the liver tissue and on the inflammatory phase after 24 hours of reperfusion; it then continued to decrease up to day 7 post-reperfusion. Afterward, it continued to rise slightly up to day 14 post-reperfusion. This trend was in parallel with the recovery of the liver damage. MiR-21 expression level in the liver and blood is a predictor of the extent of I/R injury.

Leukemia inhibitory factor (LIF) is a multi-functional cytokine secreted from cells such as lymphocytes and hepatocytes. This study aimed to evaluate the effect of LIF on natural killer group 2 member D (NKG2D) receptors' expression and presentation on natural killer (NK) cells. For this purpose, peripheral blood mononuclear cells taken from 4 young male healthy blood donors were isolated and the effect of LIF (25 ng/mL) after 12, 24, and 48 hours of incubation, on NKG2D receptors expression and presentation was investigated using flow cytometry and real-time-polymerase chain reaction (PCR). All of the steps of the experiment were performed in duplicate. After periods of 12, 24, and 48 hours, LIF reduced both the expression and presentation of the NKG2D receptor on NK cells. The results suggest that this cytokine has a direct modulating activity on the body’s immune response through suppression of NKG2D receptor expression and presentation on NK cells.

Bacillus Calmette Guerin (BCG) was designed for protecting children against tuberculosis. Also, it can protect against other infectious diseases through the induction of trained immunity. Due to its heterologous protective effects, the BCG vaccine has been proposed as a treatment option for coronavirus disease-2019 (COVID-19). Epidemiological studies have found that countries without BCG vaccination policy have experienced higher mortality rates related to COVID-19 infection than those with BCG vaccination policy. However, there are some confounding factors such as age, population intensity, immigration, the pandemic phase, and data accuracy that may affect these results. Therefore, this hypothesis should be evaluated by clinical trial studies. Large-scale clinical trials are in progress to investigate if the BCG vaccine could be used as a useful tool for protection against COVID-19 infection.

Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel anti-inflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity. Blood specimens were collected from two groups including 23 newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores>5 were higher than those with WOMAC scores<40, and VAS scores<5 (p=0.026 and p=0.035, respectively). The IL-38 levels in OA patients with body mass index (BMI)<25 were also significantly higher than in patients with BMI>25 (p=0.05). According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner. The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.

Hereditary angioedema (HAE) is characterized by recurrent attacks of skin and mucosal swelling in any part of the body including the digestive and respiratory tract which generally improve spontaneously within 12-72 hours. The underlying mechanism in HAE is related to bradykinin dysregulation which causes these attacks not to respond to common treatment strategies including epinephrine or corticosteroid. There are several types of HAE with different etiology but with the same clinical picture. Type 1 is due to the deficiency of C1 Inhibitor (C1-INH) protein and type 2 is related to dysfunctional C1-INH protein. The third type of HAE which comprises the minority of cases is associated with the normal amount and function of C1-INH protein. The presented case in this report was a 15-years old girl with a history of spontaneous angioedema attacks from the age of 14. The frequency of attacks was initially every two months but consequently increased to every two weeks after using some hormonal medications for ovarian cyst. Each episode has lasted around 10 days without any symptoms in between. Complement studies including C4, C1q, and C1-INH protein, both quantitative and qualitative, were reported as normal. A genetic assessment revealed a mutation in the exon 9 on the gene related to factor XII, hence the diagnosis of HAE type 3 was confirmed. This was a rare type of angioedema with normal amount and function of C1-INH protein which is predominantly seen in women during periods of imbalanced estrogen increments like pregnancy, lactation, and menopause, and hence it is responsive to hormonal manipulation strategies such as the use of progesterone containing medications.

Pharmacological anisocoria is a rare but benign condition. This paper presents an eleven-year-old patient with asthma who developed ipratropium bromide-associated anisocoria during nebulizer treatment. Hypotheses regarding the possible causes of anisocoria are discussed and precautions to be taken during treatment are presented. To prevent the development of anisocoria, it was found that it is important to use the appropriate mask during nebulizer treatment, to place the mask on the face properly, and, if possible, to administer drugs by closing the eyes. Further, it is recommended that patients undergo an ophthalmological examination before discharge and that they and their families be informed that the condition is temporary.