Aspirin-Exacerbated Respiratory Disease Polymorphisms; a review study.

Aspirin exacerbated respiratory disease (AERD) is a condition caused by increased bronchoconstriction in people with asthma after taking aspirin or another NSAID. Molecular analysis of the human genome has opened up new perspectives on human polymorphisms and disease. This study was conducted to identify the genetic factors that influence this disease due to its unknown genetic factors. We evaluated research studies, letters, comments, editorials, eBooks, and reviews. PubMed/MEDLINE, Web of Sciences, Cochrane Library, and Scopus were searched for information. We used the keywords polymorphisms, aspirin-exacerbated respiratory disease, asthma, allergy as search terms. This study included 38 studies. AERD complications were associated with polymorphisms in ALOX15, EP2, ADRB2, SLC6A12, CCR3, CRTH2, CysLTs, DPCR1, DPP10, FPR2, HSP70, IL8, IL1B, IL5RA, IL-13, IL17RA, ILVBL, TBXA2R, TLR3, HLA-DRB and HLA-DQ, HLA-DR7, HLA-DP. AERD was associated with heterogeneity in gene polymorphisms, making it difficult to pinpoint specific gene changes. Therefore, diagnosing and treating AERD may be facilitated by examining common variants involving the disease.

Platelet Count and IgE Level in Chronic Idiopathic Urticaria: A Case-control Study.

BACKGROUND AND AIM: Chronic Urticaria is an allergic disorder that affects about 0.5 to 5% of the population in different communities. The disease's chronic course and long-term onset impose high economic and psychological costs on communities, adversely affecting individual and social life. Platelets play a role in various pathophysiological processes, including inflammation and immunology. Growing evidence suggests that platelets are actively involved in the pathogenesis of various inflammatory disorders, including inflammatory skin diseases. This study investigated the relationship between platelet and immunoglobulin-E markers and chronic idiopathic urticaria. MATERIALS AND METHODS: In the present case-control study, for the study population, patients with chronic idiopathic urticaria were referred to the Asthma and Allergy Clinic, and their caregivers were selected as the case and control groups, respectively. In this study, the mean platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and Total IgE values were simultaneously measured in the case and control groups. After taking 5CCs of venous blood, a blood sample was sent to the laboratory for platelet and IgE marker measurements. RESULTS: 100 patients and 100 healthy persons were evaluated in this study. The mean age in the case group was 34.95, and in the control group was 35.78 years. The results showed that the mean values of PLT, MPV, PDW, and Total IgE in the case group were 12.86, 9.83, 252190, and 147.05, respectively. The mean values of PLT, MPV, PDW, and Total IgE in the control group were 16.93, 7.53, 231410, and 15.29, respectively, which was statistically significant (P = 0.001). Moreover, total IgE in the Autologous Serum Skin Test (ASST) positive group was higher than ASST negative group and was statistically significant (P = 0.001). CONCLUSION: The study results indicate the possible role of platelets in urticaria and inflammation. MPV in patients with chronic urticaria was higher than in the control group. The present study showed no significant relationship between the severity of urticaria and platelet markers, but there was a significant relationship between the severity of urticaria and ASST. Moreover, the severity of urticaria was higher in the positive skin test group.

The Prevalence of Asthma among Iranian Children and Adolescent: A Systematic Review and Meta-Analysis.

BACKGROUND: Asthma is an important reason for hospitalization in children aged under five years. Information about the current status of asthma in Iranian children can help the Iranian health sector plan carefully and prevent asthma incidence by educating the families. The present systematic review and meta-analysis is aimed at estimating asthma prevalence in Iranian children and adolescents. METHOD: Data were found using keywords such as prevalence, epidemiology, asthma, adolescent, children, pediatrics, Iran in Web of Science, Scopus, PubMed, Cochrane, and Embase databases. Three national databases, including Magiran, Barakat Pharmed Co (Iran medex), and Scientific Information Databank (SID) were searched until 1 October 2020. Cross-sectional and original studies were included in the study, and then, quality assessment was done using the National Institutes of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A pooled estimated prevalence of asthma was calculated using Der Simonian-Laird random model. Egger's test was used to evaluate publication bias. The data were analyzed using the STATA software version 16. RESULTS: 30 studies were selected and investigated. The prevalence of asthma in children and adolescents was 6% and 8%, and the prevalence in boys and girls was 9% and 8%, respectively. Among the asthma symptoms, wheezing had the most prevalence (17% in children and 19% in adolescents) and sleep disturbance had the lowest prevalence (6% in children and 6% in adolescents). CONCLUSION: The prevalence of asthma in Iranian children and adolescents is lower than in the world. Existing strategies should be pursued followed. Also, guidelines for asthma control and prevention should be considered in the future.

Evaluation of Candidate SNPs for Type 2 Diabetes Mellitus in Tohid Hospital of Sanandaj.

BACKGROUND: The allele frequency of 4 SNPs was evaluated in patients with type 2 diabetes mellitus (T2DM) and compared with healthy controls who had records in Tohid Hospital of Sanandaj. METHODS: This case-control study was performed on 100 T2DM patients and 100 healthy controls with matched gender and age. After DNA extraction, allele frequency of 4 variant genotypes was evaluated using Tetra-Arms technique. Then, logistic regression analysis was used to calculate the odds ratio. Data analysis was done using SPSS 20 software and the level of significance was less than 0.05. RESULTS: There were no significant relationships between CASQ1 rs2275703A/C and CTLA4 rs231775A/G polymorphisms and T2DM mellitus in the studied population. Also, CC and CT genotypes of the TCF7L2 rs7903146 C/T polymorphism confirmed a T2DM risk factor in the studied population. At the ATF6 rs2070150 C/G polymorphisms, the frequency of GC allele was higher in the control group than in the patient group, and these differences were also statistically significant at the level of alleles in the experimental and control groups. CONCLUSIONS: The CC and CT genotype of TCF7L2 rs7903146 polymorphism and GC genotype of ATF6 rs207015 were the risk factor for T2DM in this population.

A review on the immune responses against novel emerging coronavirus (SARS-CoV-2).

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by a newly identified coronavirus called the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) which was initially emerged in Wuhan, China in late December 2019 and then rapidly extended to other countries worldwide. COVID-19 is now known as a pandemic threat to global public health. It possesses a wide spectrum of clinical manifestations, ranging from asymptomatic infection to mild, moderate, and ultimately severe pneumonia accompanied by multi-organ system dysfunction that can cause the death of the afflicted patients. The host immune system plays a critical role in defending against potentially pathogenic microorganisms such as coronaviruses, and it eliminates and eradicates these invading agents by triggering effective immune responses. However, there exists evidence indicating that in critically ill cases of the COVID-19, dysregulated immune responses and hyper-inflammation lead to acute respiratory distress syndrome (ARDS) and multi-organ failure. Achieving a profound understanding of the pathological immune responses involved in the pathogenesis of COVID-19 will boost our comprehending of disease pathogenesis and its progression toward severe form, contributing to the identification and rational design of effective therapies. In this review, we have tried to summarize the current knowledge regarding the role of immune responses against SARS-CoV-2 and also give a glimpse of the immune evasion strategies of this virus.

Immune semaphorins: Crucial regulatory signals and novel therapeutic targets in asthma and allergic diseases.

Asthma and allergic diseases are a group of chronic inflammatory disorders that arise as a result of excessive responses of the immune system against intrinsically harmless environmental substances. It is well known that substantial joint characteristics exist between the immune and nervous systems. The semaphorins (Semas) were initially characterized as axon-guidance molecules that play a crucial role during the development of the nervous system. However, increasing evidence indicates that a subset of Semas, termed "immune Semas", acting through their cognate receptors, namely, plexins (Plxns), and neuropilins (Nrps), also contributes to both physiological and pathological responses of the immune system. Notably, immune Semas exert critical roles in regulating a broad spectrum of biological processes, including immune cell-cell interactions, activation, differentiation, cell migration and mobility, angiogenesis, tumor progression, as well as inflammatory responses. Accumulating evidence indicates that the modification in the signaling of immune Semas could lead to various immune-mediated inflammatory diseases, ranging from cancer to autoimmunity and allergies. This review summarizes the recent evidence regarding the role of immune Semas in the pathogenesis of asthma and allergic diseases and discusses their therapeutic potential for treating these diseases.

Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease.

Aim: Stem cell factor (SCF) may be associated with inflammatory processes leading to aspirin-induced asthma. This study evaluated the relationship between serum level of SCF and its soluble receptor with aspirin-induced asthma. Methods & materials: Twenty-five patients and 25 healthy controls were enrolled in this study. The concentration of SCF and mast/stem cell growth factor receptor (C-kit) was determined in serum samples. Spirometry and rhinometry were performed to determine the severity of the disease. p < 0.05 were considered significant. Results: The serum levels of SCF and C-kit receptor were significantly higher in the case group. The serum SCF and C-kit level had a significant positive correlation with the severity of asthma, disease duration and nasal obstruction. Conclusion: Our findings suggest that SCF and C-kit receptors have a direct effect on the severity of aspirin-induced asthma.

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is one of the predominant antibody deficiency disorders, some evidence of which indicates that chromosome instability is present in these patients. An increased risk of cancer in patients with CVID has been documented. This study was undertaken to highlight radiation sensitivity in CVID patients and to clarify the genetic basis of this defect in these cases. Stimulated lymphocytes of the studied subjects were exposed to low-dose gamma-rays in the G2 phase or the G0 phase of the cell cycle and chromosomal aberrations were scored. Lymphocytes of healthy individuals, ataxia telangiectasia (AT) cases and a group of acute lymphoblastic leukemia (ALL) patients were investigated in the same way as controls. By two methods of analysis (one-way ANOVA and unpaired t-test), the CVID cases were significantly more radiosensitive than healthy controls based on the results of the G2 and the G0 assays. First-degree relatives of CVID patients were radiosensitive by the micronucleus assay which showed a significant difference as compared with normal controls (p = 0.001). In conclusion, this study may support that chromosomal radiosensitivity in CVID patients is a marker of genetic predisposition to the disease. The results might be a clue to describe the increased risk of cancer in CVID patients.