Iranian journal of allergy, asthma, and immunology最新文献

Measuring the performance of small airways dysfunction is challenging due to their relative inaccessibility with conventional methods. In recent years, spirometry and impulse oscillometry (IOS) methods have been widely used for their evaluation. The aim of this study was to investigate the relationship between spirometric parameters and IOS in newly diagnosed asthma (NDA) patients. In this cross-sectional study, 100 NDA patients who referred to the allergy Clinic of Masih Daneshvari Hospital between 2021 and 2023 were enrolled. IOS and spirometry tests were performed for all patients. Spirometry measures included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, and forced expiratory flow (FEF25-75). IOS criteria included R5%, R20%, R5-R20%, X5%, Ax% and FRES. The relationship between spirometry and IOS parameters was evaluated. The mean age was 22.6±9.5 years. None of the 2 techniques had a significant relationship with disease severity. FVC, FEV1/FVC and FEF25-75 indices had a significant positive correlation with all other IOS indices except for Ax. In the comparison of FEF25-75 parameter in spirometry, 4 IOS indices including R5, R20, R5-R20 and X5 had appropriate sensitivity and specificity for predicting asthma. In the comparison of FEF25-75 parameter in spirometry, 4 IOS indices including R5, R20, R5-R20 and X5 had appropriate sensitivity and specificity for predicting asthma. The sensitivity and specificity of R5 for asthma diagnosis were 0.85 and 0.73, respectively. Further multicenter studies with larger sample sizes are recommended to confirm these results.

The quantity and quality of anti-Spike (anti-S) antibodies, rapidly elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are necessary for understanding the immune response induced by infection. Antibody avidity is a good indicator of the quality of antibody response. Interleukin (IL)-21 and IL-27 are two cytokines that play vital roles in the affinity maturation process. Therefore, we decided to investigate whether there are any relationships between the avidities of antibodies against spike and nucleocapsid (N) antigens of SARS-CoV-2 and serum levels of these cytokines in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. Forty symptomatic COVID-19 patients and 40 asymptomatic carriers were enrolled. Anti-S and anti-N IgG avidity indices (AIs) were determined using a modified enzyme-linked immunosorbent assay (ELISA). Serum levels of IL-21 and IL-27 were quantified by specific ELISA kits. AI values of both anti-S and anti-N IgG were lower in the symptomatic group compared to asymptomatic cases, while only that of anti-N IgG was statistically significant. For IL-21 and IL-27 serum levels, no significant difference between the two groups was shown. Also, we could not find any correlations between cytokine levels and antibody AI values. However, an inverse correlation between anti-S AI value and IL-27 serum level was found in asymptomatic patients. Our study suggests that serum levels of IL-21 and IL-27 cannot predict differences in anti-S and anti-N IgG avidity between symptomatic and asymptomatic COVID-19 patients.

Latent transforming growth factor-β binding protein-2 (LTBP2) plays a significant role in tissue fibrosis. This research aimed to elucidate whether LTBP2 influences the progression of diabetic nephropathy (DN) through the phosphatidylinositol 3-kinases/protein kinase B (PI3K/Akt)/nuclear factor kappa-B (NF-κB) pathway. The HBZY-1 cells were exposed to high glucose to create diabetic nephropathy cell model. LTBP2 levels were examined by Western blot and immunofluorescence. After verifying the transfection efficiency of si-LTBP2, cell counting kit-8, 5-ethynyl-2-deoxyuridine staining, Western blot, flow cytometry and immunofluorescence were utilized to assess the proliferation, apoptosis and fibrosis of HBZY-1 cells, respectively. Collagen deposition was also detected by Sirius red staining, and inflammatory factors levels were determined by Elisa. PI3K/Akt/NF-κB pathway activators were applied to explore whether LTBP2 silencing could play a role in DN by modulating this pathway. After treatment with high glucose, the expression of LTBP2 was elevated in HBZY-1 cells. LTBP2 silencing hindered the aberrant proliferation of HBZY-1 cells, with no significant effect on apoptosis; meanwhile, it reduced fibrosis, decreased collagen content, and decreased inflammatory factors levels in HBZY-1 cells. Following treatment with high glucose, the PI3K, Akt, and p65 phosphorylation levels were increased, whereas silencing LTBP2 reduced them. Activators of the PI3K/Akt/NF-κB pathway weakened the inhibition of LTBP2 silencing on cell proliferation, fibrosis, and inflammation. In conclusion, silencing of LTBP2 weakened the proliferation, fibrosis, and inflammation of HBZY-1 cells treated with high glucose by hindering the PI3K/Akt/NF-κB pathway. This research offers a new reference for the targeted therapy of DN.

Osteoporosis (OP), a widespread musculoskeletal disorder characterized by fragile bone fractures, has seen increasing attention regarding immune infiltration-related genes. These genes show significant predictive value in solid tumor prognosis and are now being explored for their roles in musculoskeletal diseases. This study identified osteoporosis-associated differentially expressed immune genes (OP-DEGs) by analyzing the overlap between OP-differentially expressed genes and immune genes. To elucidate the functional implications of these genes, pathway enrichment analysis was conducted using Gene Ontology and KEGG databases. Additionally, Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were employed to explore underlying mechanisms. A competitive endogenous RNA (ceRNA) network was constructed for critical OP-related immune genes, and immune infiltration analysis investigated micro-environmental characteristics. The diagnostic effectiveness of OP was evaluated using ROC curves. Finally, RT-PCR determined the expression levels of 15 key OP-related immune genes in OP and control groups. The study identified 29 OP-DEGs. Extensive bioinformatics analysis pinpointed 15 key genes that could serve as potential biomarkers for OP diagnosis. RT-PCR results revealed significantly increased expression of VEGFA, HMOX1, RARA, CXCL10, hsa-miR-129-2-3p, OIP5-AS1, and HCG18 in the OP group compared to controls. Our findings suggest that these immune-related genes may predict OP prognosis and offer new perspectives for early prevention and intervention strategies. The identification of specific immune genes involved in OP development highlights their potential as therapeutic targets for further investigation.

The cardinal features of asthma include airway inflammation, airway hyper responsiveness (AHR) and airway remodeling. Exosomes help orchestrate the immune response and contain microRNAs (miRNAs) such as miRNA-155 and miRNA-221 which play significant roles in the pathogenesis and exacerbations of severe asthma. In this study, we aimed to investigate the exosomal expression of miRNAs (155, 221) in the serum of severe asthma patients. Eighteen moderate-to-severe asthma patients and eighteen healthy subjects were recruited for this study. Serum exosomes were isolated and characterized according to their shape, size, and exosomal markers by transmission electron microscopy, dynamic light scattering (DLS) and flow cytometry, respectively. Exosomal miRNA extraction and quantitative real-time PCR (qRT-PCR) were used to measure miR-155 and miR-221. Besides the forced expiratory volume in 1 second and forced vital capacity (FVC) were evaluated in the patient groups. Round exosomes with a mean size of 25.8 nm were isolated from serum of asthmatic patients. Flow cytometry shows high expression of CD63 and CD81 on isolated exosomes. Serum exosomes from severe asthma patients and healthy donors contained miR-155 and miR-221 but miR-155 and miR-221 expression levels were significantly increased in severe asthma patients. There was a positive correlation between miR-221 expression and FVC). Receiver operating characteristic (ROC) analysis indicated that miR-155 and miR-221 had an excellent diagnostic efficiency in predicting asthma (AUC=0.91 and AUC=0.76, respectively). Serum exosomal miR-155 and miR-221 may be a potential biomarker for severe asthma. However, the results need to be validated in another cohort, and further studies with larger samples size should be conducted on the effects of these miRNAs on effector cells.

Non-Small Cell Lung Cancer (NSCLC) patients undergoing Immune Checkpoint Inhibitors (ICIs) therapy exhibit diverse clinical outcomes. The Lung Immune Prognostic Index (LIPI) may emerge as a potential prognostic marker. This study systematically reviews and meta-analyzes the prognostic value of LIPI in predicting the clinical efficacy of ICIs therapy for NSCLC patients. A thorough literature review was performed using the Cochrane Library, Web of Science, PubMed, and Embase, following PRISMA guidelines. Studies assessing LIPI's predictive value in NSCLC patients treated with ICIs were included. Effect sizes were aggregated utilizing a fixed-effects model. The studies featured in the review were appraised using the Newcastle-Ottawa Scale for quality assessment. Eight studies were incorporated into the meta-analysis, encompassing various treatment lines and ICIs. No substantial heterogeneity was detected across the studies. The meta-analysis revealed that the low-risk group exhibited significantly extended overall survival (OS) (HR=3.18, 95%CI: 2.78~3.59 and progression-free survival (PFS) (HR=1.60, 95%CI: 1.4~61.74, underscoring the predictive significance of LIPI for NSCLC patients treated with ICI therapy. No significant publication bias was detected. LIPI demonstrates potential as a prognostic marker for NSCLC patients receiving ICI therapy, contributing to the development of therapeutic strategies. Further prospective researches are required to investigate its relationship with factors such as tumor mutational burden, PD-L1 and PD-1.

Ataxia Telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disease caused by mutations in the ataxia telengiectasia mutated (ATM) gene. The gene is on chromosome 11q22-23 and codes for the protein kinase ATM, which plays an essential role in DNA damage repair. In this study, we review the clinical characteristics of 13 A-T patients, 2 of whom displayed novel mutations. Thirteen patients with ataxia-telangiectasia from 10 unrelated families were referred to  Immunology, Asthma and Allergy Research Institute, Tehran, Iran. After clinical confirmation, blood samples were collected from the patients and their parents. Genetic analysis for 8 patients was conducted using whole-exome sequencing; in the other 3 patients, polymerase chain reaction was used, followed by sequencing. We identified 11 different mutations in the ATM gene. Two patients had mutations as compound heterozygous, while 9 other patients were homozygous for the mutations. Among these, 2 likely pathogenic mutations (ie, c.2639-1G>A and c.7940_7970del​TTCCAGCAGA​CCAGCCAATT​ACTAAACTTAA) have not been reported. Our study highlights the significance of next-generation sequencing techniques in identifying novel ATM mutations in A-T patients. Although all reported A-T mutations reside in 1 gene, the absence of a mutation hotspot for this gene necessitates the use of next-generation sequencing techniques. Specifically, we identified 2 mutations that have not been reported previously, emphasizing the importance of continued research in this area. This study provides new insights into the genetic underpinnings of A-T and underscores the potential clinical implications of identifying novel mutations.

Diabetic nephropathy is a microvascular complication that leads to renal injury. Oxymatrine (OMT) is a matrine alkaloid and has been shown to ameliorate diabetic nephropathy. However, it is still unknown whether its mechanism involves podocytes, which play a critical role in diabetic nephropathy. High glucose-induced podocytes (MPC5) were treated with OMT, the NOD-like receptor protein 3 (NLRP3) inhibitor MCC950, and the sirtuin 1 (SIRT1) inhibitor EX527. The effects on podocyte proliferation and apoptosis were assessed using cell counting kit-8 and flow cytometry. Immunofluorescence staining was performed to detect the expression of podocyte-associated proteins, NLRP3 inflammasome, and SIRT1. The levels of interleukin (IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay. Additionally, Western blot analysis was conducted to evaluate podocyte-related proteins, NLRP3 inflammasome-dependent pyroptosis-related proteins, and SIRT1/nuclear factor kappa B (NF-κB) pathway proteins, aiming to elucidate the mechanisms by which OMT improves podocyte injury. OMT significantly promoted the proliferation of podocytes exposed to high glucose, inhibited their apoptosis, increased the levels of nephrin, Wilms tumor 1, podocin, and zonula occludens-1, and reduced pyroptosis-related proteins, IL-1β, and IL-18 (p < 0.05). It also increased SIRT1 and decreased the acetylation of NF-κB p65 (p < 0.05). The NLRP3 inhibitor MCC950 reduced podocyte pyroptosis under high glucose conditions, while the SIRT1 inhibitor EX527 reversed the protective effects of OMT on NLRP3 inflammasome-dependent pyroptosis and podocyte injury. OMT ameliorates high glucose-induced podocyte injury by regulating the SIRT1/NF-κB pathway and inhibiting NLRP3 inflammasome-dependent pyroptosis.

The severity of coronavirus disease 2019 (COVID-19) varies significantly among individuals, which indicates the impact of individual differences on disease. Emerging evidence suggests that genetic factors play a crucial role in determining the severity of the disease. For instance, variants in the interferon-gamma (IFN-γ) gene, such as the +874 T/A single nucleotide polymorphism (SNP), have been linked to altered immune responses and may influence the severity of COVID-19. We aim to determine the influence of the IFN-γ +874T/A SNP on the clinical outcomes of COVID-19 patients. We investigated the SNP at position +874 in the promoter region of the IFN-γ gene in 416 individuals (206 critically ill COVID-19 patients and 210 healthy controls) in northwestern of Iran. Genomic DNA was extracted from the blood leukocytes of the patients, and the SNP was analyzed using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. The AA genotype was significantly more frequent in critically ill COVID-19 patients than in healthy controls. Conversely, the AT and TT genotypes were more common in healthy controls. Furthermore, the A allele was more frequent in critically ill patients than in healthy controls, while the T allele was more frequent in healthy controls compared to critically ill patients. Our study identified the IFN-γ +874T/A SNP as a significant genetic factor influencing COVID-19 severity. This finding underscores the critical role of genetic factors in disease severity and highlights the importance of personalized medicine in managing COVID-19.

Regulatory T cells (Tregs) are central to establishing an immunosuppressive tumor microenvironment (TME), which promotes cancer progression and influences therapeutic outcomes. However, the prognostic significance of Treg-related genes (TRGs) in predicting immunotherapy response in melanoma remains insufficiently characterized. This study seeks to elucidate the role of TRGs in the antitumor immune response of melanoma. The ordinary transcriptome and single-cell RNA sequencing (scRNA-seq) data were obtained from the gene expression omnibus and the cancer genome atlas databases. A multi-tiered quality control process was applied to scRNA-seq data, followed by cell annotation, cell-cell communication, and enrichment analysis to investigate Treg function in the melanoma microenvironment. Weighted gene coexpression network analysis (WGCNA) was employed to identify modules associated with Treg infiltration. Key prognostic genes were identified using univariate Cox regression analysis and integrated into a prognostic model through least absolute shrinkage and selection operator and stepwise regression methods. The analysis revealed a Treg-related gene signature (TRGS) comprising CHD3, FOSB, SEMA4D, PSME1, FYN, PRKACB, and ARID5A. Higher TRGS-based risk scores were significantly associated with worse prognoses, immune cell infiltration, and stromal scores. TRGS was identified as an independent prognostic indicator for melanoma, offering novel insights into the role of Tregs in modulating the TME. This study highlights the potential clinical utility of TRGs in melanoma diagnostics and personalized immunotherapy, providing a robust foundation for future therapeutic strategies.