Iranian Journal of Allergy, Asthma and Immunology
Volume:22 Issue: 3, Jun 2023

Coronavirus disease 2019 (COVID-19), described as World War 3, is the current worldwide health challenge and nearly all countries have so far faced this disaster. There is still no cure because of the complicated pathogenesis, however, there are several studies on track investigating different aspects of the immune response to the virus. In this review, we will provide an overview of recent investigations that have analyzed immune cells in patients with COVID-19. We will then discuss the differences in immune profiles between healthy controls and various clinical presentations, including asymptomatic, mild, moderate, and severe cases.

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into  Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue–derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127-  Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo–treated PBMCs. The concentration of IL‐10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of  Tregs, potentiating its therapeutic effects in COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic has been the most significant health concern in recent years, with respiratory symptoms being the most prominent. In children, asthma is the most prevalent chronic disease. Due to the similarities between the symptoms of these two conditions, we sought to assess the general health status of pediatric patients with asthma and their COVID-19-related difficulties during the first year of the pandemic in Iran. We collected data for this study by administering a questionnaire to the parents of 200 children with asthma who were registered in the database of the Asthma Clinic at a tertiary medical center in Tehran, Iran. Forty-five (22.5%) of 200 patients were suspected of having COVID-19, 11 (24.4%) underwent polymerase chain reaction (PCR) testing, and 10 (90.9%) assays were positive. During the first year of the pandemic, 41 patients (20.5%) were referred to a medical center at least once, with 31.7% due to an asthma attack. One hundred eighty-nine patients (94.5%) reported an improved disease status than the previous year, and only 31 patients (15.5%) were using asthma-related medications such as Salbutamol. The estimated mean Asthma Control Test (ACT) scores for two age categories, 4-11 years and 12-18 years, were 25.55±2.27 and 23.28±3.31, respectively, indicating satisfactory disease control. In the majority of our study population, asthma control was acceptable. However, the pandemic caused a significant increase in the anxiety levels of patients and their parents.

Compared to common asthma, obese asthma is difficult to control. Previous studies have shown that vitamin D (Vit D) has a therapeutic effect on asthma. Nevertheless, the action mechanism of Vit D for obese asthma are not well known. In this study, we, therefore, induced obesity and established an obese asthma mouse model using ovalbumin (OVA) stimulation and applied treatment with Vit D (100 ng/kg). Accordingly, thirty mice were randomly divided into 5 equal groups of normal control, asthma, obese asthma, asthma+Vit D, and obese asthma+ Vit D. The levels of inflammatory factors and adipokines were measured by the ELISA assay; then the quantitative reverse transcription PCR (qRT-PCR) method was used to evaluate the expression of high mobility group box 1(HMGB1) and receptor for advanced glycation end products [RAGE] genes.T he results showed that OVA sensitization significantly increased airway resistance, the levels of inflammatory cytokines, and HMGB and RAGE expression in asthmatic and obese asthmatic mice, as compared to the control group. Also, these changes in the obese asthmatic group were notably higher than those in the asthmatic one. In addition, the treatment of asthmatic and obese asthmatic mice with Vit D significantly reduced the raw, serum and BALF levels of inflammatory cytokines, as well as the expression of HMGB1 and RAGE mRNA. To conclude, the present study showed that vitamin D might attenuate lung injury by up-regulating HMGB1 and RAGE expression. Our findings, thus, may offer new concepts and approaches for the treatment and prevention of obese asthma.

Asthma is a common chronic allergic disease that affects a significant percentage of the world’s population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats. Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated. The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices.  Inhalation of simple and niosomal forms of myrtenol improved the detrimental changes in the asthmatic lung. The niosomal form induced more prominent anti-asthmatic effects comparable to those of budesonide.

Ziziphus Jujuba Mill (Z.J) is a well-known ethnomedical source of biologically active compounds with anti-inflammatory effects. However, its significance in acute lung injury (ALI) has never been studied. The present study aimed to explore whether Z.J could attenuate lipopolysaccharide (LPS)-induced inflammatory responses in an experimental model of ALI. Male BALB/c mice received an intratracheal administration of LPS (n=32) or phosphate buffer saline (PBS) (control, n=8). Within 1, 11, and 23 h post-LPS injection, mice were randomly assigned to receive intraperitoneal treatments of saline, dexamethasone (2 mg/kg), and 100 and 200 mg/kg of Z.J extracts, respectively. 24 h after intratracheal administration of LPS, bronchoalveolar lavage fluid and lung tissues were harvested and assessed for inflammatory cell influx, tumor necrosis factor-α (TNF-α) levels, and histological assessments. Treatment with Z.J extracts (100 and 200 mg/kg) and dexamethasone effectively reduced LPS-induced neutrophil and other inflammatory cell influx into the lung tissue compared to the untreated group. additionally, both doses of Z.J extracts (100 and 200 mg/kg) significantly ameliorated the lung wet-to-dry ratio and histopathological damage. Furthermore, compared to the untreated ALI mice, Z.J extract at the highest dose could significantly reduce the TNF-α level.   The present findings indicated that Z.J could effectively ameliorate LPS-induced ALI inflammatory responses and might be considered a promising alternative therapy for the ALI phenotype.

Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy. We aim to obtain a better understanding of the clinical status and disease burden of patients with asthma in China. A retrospective study was carried out based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (available data from 38 hospitals). The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to Global Initiative for Asthma 2020 (GINA 2020). The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) at emergency department visits had lower frequencies of exacerbations compared with non-ICS/LABA-treated patients. The incidence rates for 1, 2, 3, and 4 exacerbation of the patients treated with ICS/LABA are lower than those treated without ICS/LABA (14.49 vs. 15.01%, 11.94% vs. 19.12%, 6.51% vs.12.92% and 4.10% vs. 9.35%). The difference got a statistical significance Chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations (mean costs are ￥3,339.67 vs. ￥968.45 separately).  These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for people living with asthma.

T cell dysregulation and shift to T helper 2 responses, boosting tumor microenvironment support, contributes to the survival of leukemic B cells in Chronic Lymphocytic Leukemia. Interleukin (IL)-25 is involved in the initiation of T helper 2 cell responses. Signal transduction of IL-25 begins with the heterodimer receptor (IL-17RA/IL-17RB). The presence of IL-25 in the tumor microenvironment may affect the supportive effects of T cells in the surrounding tumor cell environment. The purpose of this study was to evaluate the role of IL-25 in the biology of CLL. IL-17RB expression in CD3+ and CD19+ cells was assessed in isolated peripheral blood mononuclear cells (PBMCs) of nine CLL patients and nine healthy subjects by real-time polymerase chain reaction and flow cytometry. B cells were positively enriched from PBMCs using magnetic-activated cell sorting (MACS). PBMCs and purified leukemic B cells were cultured with recombinant human IL-25 (20ng/ml) for 72 hours, then the viability and apoptosis of cultured cells were measured by MTT assay and AnnexinV/7AAD. Furthermore, the levels of CD69 expression on T lymphocytes and IL-17RB in T and B cells were determined by flow cytometry. The basal level of IL-17RB expression in CLL patients was significantly higher than that in control individuals. In addition, the percentage of IL-17RB+/CD3+, IL-17RB+/CD19+ cells and CD69+/CD3+ cells increased after 72 hours of culture with IL-25 in CLL patients compared to healthy subjects. IL-25 also reduces the apoptosis rate of tumor cells. We found that IL-25 could stimulate T cells in CLL patients and lower B cell death. This suggests that IL-25 might have a role in enhancing the survival of tumor cell by expressing receptors for inflammation, such as IL-17RB, and might be involved in the development of CLL.

Evaluation and monitoring of pemphigus vulgaris (PV) typically involve autoantibody detection by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF). We aimed to determine the levels of antipemphigus immunoglobulin (Ig) G autoantibodies using ELISA and IIF (as standard biomarkers), and compare it to prolactin, macrophage migration inhibitory factor (MIF), and C-reactive protein (CRP) (as nonstandard biomarkers) to determine which of these non-standard biomarkers is appropriate for PV monitoring. The experiment was performed before and during therapy. Anti-Dsg immunoglobulin G autoantibodies were measured using ELISA and IIF (as standard biomarkers) versus prolactin, MIF, and CRP (nonstandard), before 1 and 3 months after the treatment. Before beginning the treatment, the severity of the disease was determined using the pemphigus disease area Index (PDAI). We enrolled 60 newly diagnosed patients with PV (32 men and 28 women; mean age=43.8±14.2 years). Before treatment, the levels of anti-Dsg1, anti-Dsg3, and IIF were high and had a significant relationship with PDAI. PDAI also had a connection with the levels of CRP and prolactin. The anti-Dsg1, anti-Dsg3, IIF, and CRP titers decreased in patients treated with conventional (prednisolone plus azathioprine) and rituximab therapy during and after treatment. In conclusion, anti-Dsg1, anti-Dsg3, and IIF autoantibody titers remain standard biomarkers for assessing disease activity, severity, and PV monitoring. The trend of CRP was similar to that of anti-Dsg1, anti-Dsg3, and IIF. Thus, CRP may be used for PV monitoring.

Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis that mostly affects children, and previous studies have indicated that genetic factors may influence disease susceptibility. The aim of this study was to evaluate a possible association of three interleukin-2 (IL-2) gene polymorphisms (rs3136534, rs2069776, and rs2069762) with HSPN in the Chinese population. A total of 81 patients with HSPN and 200 healthy children were enrolled. The distribution of genotypes, allelic frequencies, and haplotype frequencies among the three IL-2 polymorphisms were analyzed using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Compared to the healthy controls, genotyping analysis demonstrated rs3136534 was associated with a decreased HSPN risk in the dominant inheritance model (G/T+T/T vs. G/G; OR, 0.54; 95% CI, 0.31–0.93). However, the frequency of the T allele and haplotypes of rs3136534 showed no statistical significance. For the frequency of genotype, allele, and haplotype of the rs2069776 and rs20697622 polymorphisms, no significant differences were observed between HSPN patients and controls. Our results suggest that the rs3136534 polymorphism of the IL-2 gene is associated with susceptibility to HSPN in Chinese children.