Iranian Journal of Allergy, Asthma and Immunology https://publish.kne-publishing.com/index.php/IJAAI <p class="text">The Iranian Journal of Allergy, Asthma and Immunology (IJAAI), a scientific and research journal, seeks to publish original papers, selected review articles, case reports, and other articles of special interest related to the fields of asthma, allergy and immunology. The Journal is an official publication of the Iranian Society of Asthma and Allergy (ISAA), which is supported by Immunology, Asthma and Allergy Research Institute (IAARI) and published by Tehran University of Medical Sciences (TUMS). The Journal seeks to provide its readers with the highest quality materials published through a process of careful peer reviews and editorial comments. All papers are published in English.</p> <p class="text"><strong data-stringify-type="bold">All the manuscripts should be submitted through the Journal Primary Website at <a href="https://ijaai.tums.ac.ir/index.php/ijaai">https://ijaai.tums.ac.ir/index.php/ijaai</a></strong></p> Knowledge E en-US Iranian Journal of Allergy, Asthma and Immunology 1735-1502 Allergic Diseases and Head and Neck Cancer: A Systematic Review and Meta-analysis https://publish.kne-publishing.com/index.php/IJAAI/article/view/20794 <p>Allergic disorders such as asthma, atopic dermatitis, and allergic rhinitis affect a large portion of the global population. The relationship between allergies and cancer has been studied extensively, but results remain inconsistent for head and neck cancer. The aim of this meta-analysis is to evaluate whether there is a negative association between allergic disorders and head and neck cancer. A systematic search of five databases was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort- and case-control studies examining allergies and head and neck cancer were included. Random-effect and fixed-effect models were used to calculate pooled relative risk, with heterogeneity assessed via the I2 and Cochrane’s Q-test. Subgroup and sensitivity analyses were performed to explore variations by study design, allergy type, and cancer site. Twenty-five studies with 3.6 million participants were included. No significant overall association was found between allergic diseases and head and neck cancer (meta-RR: 0.89; 95% confidence intervals (CI): 0.76–1.05). Subgroup analyses revealed protective effects for asthma (meta-RR: 0.81; 95% CI: 0.70–0.95) and food allergies (meta-RR: 0.73; 95% CI: 0.54–0.99). Allergic rhinitis showed negative associations with oropharyngeal cancer (meta-RR: 0.76; 95% CI: 0.69–0.84) and hypopharyngeal cancer (meta-RR: 0.65; 95% CI: 0.55–0.78), but a positive association with nasopharyngeal cancer (meta-RR: 1.67; 95% CI: 1.15–2.43). These findings suggest complex relationships between allergies and head and neck cancer, with negative and positive associations varying by allergy type and cancer site. Further research is needed to clarify these associations.</p> Daniel Karlsson Amanj Saber Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20794 Evaluating the Efficacy of Intranasal Montelukast in Pediatric Acute Asthma Attacks: A Single-blinded, Placebo-controlled Clinical Trial https://publish.kne-publishing.com/index.php/IJAAI/article/view/20795 <p>Asthma is a common chronic respiratory disease in children, often leading to acute exacerbations marked by dyspnea, cough, and wheezing, which frequently necessitate emergency medical care. While standard therapies are effective, the exploration of novel drug delivery routes continues. Oral montelukast is a recognized treatment, but the efficacy of its intranasal formulation for acute attacks remains underexplored. This study aimed to evaluate the clinical effectiveness of intranasal montelukast as an adjunct therapy for pediatric asthma exacerbations.</p> <p>A single-blinded, placebo-controlled, single-center trial was conducted involving children aged 2-12 years hospitalized with moderate to severe acute asthma. Participants were randomized to receive either intranasal montelukast or a placebo alongside standard care. Key outcomes, including the Pulmonary Index Score (PIS), respiratory rate, oxygen saturation, and length of hospital stay, were systematically assessed.</p> <p>The analysis of 25 patients in each group revealed no significant baseline differences. The intranasal montelukast group demonstrated a statistically significant and sustained reduction in PIS scores at critical intervals (8, 12, and 24 hours) compared to the placebo group. Improvements in respiratory rate and oxygen saturation were also more pronounced with the active treatment. Notably, the mean hospital stay was significantly shorter for the montelukast group (2.16 days) than the placebo group (3.12 days).</p> <p>In conclusion, intranasal montelukast shows significant promise as an effective adjunct therapy for acute pediatric asthma, correlating with accelerated clinical improvement and a reduced duration of hospitalization. These encouraging results justify further investigation through larger, multicenter trials to definitively establish its efficacy and safety profile.</p> Morteza Sadinejad Nilufar Amini Elham Tavakoli Ali Mohammad Sabzghabaee Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20795 Assessment of Rigid Nasopharyngoscopy Beyond the Nasal Cavity in Diagnosis of Immune-mediated Nasopharyngeal Allergic Diseases https://publish.kne-publishing.com/index.php/IJAAI/article/view/20796 <p>Rigid nasopharyngoscopy is a valuable diagnostic method for immune-mediated allergy conditions, particularly for children aged≤6 years. In addition to evaluating the structural characteristics of the nasal cavity, the procedure also reveals inflammatory activity in the nasopharyngeal framework.</p> <p>This study assessed 110 pediatric patients between 2 and 6 years old who presented with suspected allergic conditions. Rigid nasopharyngoscopy was performed, and its diagnostic performance was high with 85.45% sensitivity, 78.18% specificity, and an overall diagnostic accuracy of 83.00%, which supports its role in diagnosing and ruling out allergic disorders.</p> <p>The findings revealed strong associations between mucosal erythema, cobblestoning, and mucosal secretions with symptoms like nasal obstruction and postnasal drip. These signs have proven to be reliable indicators of inflammation and chronic irritation in this age group. The procedure was well tolerated, and over 85% of children experienced no adverse effects.</p> <p>Minor discomfort and nasal bleeding were reported in a small number of cases. Taken together, the results show that rigid nasopharyngoscopy is an essential diagnostic modality for early detection of allergy conditions in the pediatric population.</p> <p>&nbsp;</p> Hongbo Wang Panru Zhu Jiangqiao Geng Pin Yu Jiejing Dong Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20796 Association of Systemic Immune Inflammation Index and Pan-immune Inflammation Value with Prognosis in Idiopathic Membranous Nephropathy https://publish.kne-publishing.com/index.php/IJAAI/article/view/20797 <p>Idiopathic membranous nephropathy (IMN) presents a heterogeneous clinical course, with approximately 30% to 40% of patients experiencing spontaneous remission, while others respond poorly to treatment. This study aims to identify reliable biomarkers for risk stratification in IMN patients.</p> <p>We conducted a prospective observational study involving 187 patients with IMN from February 2022 to February 2024. Patients were categorized into remission and non-remission groups based on clinical outcomes one year post-treatment. Comparative analyses revealed that the non-remission group exhibited significantly higher incidences of hypertension, elevated 24-hour urinary protein, higher serum creatinine levels, and increased inflammatory markers, including the systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV). Conversely, the estimated glomerular filtration rate (eGFR) and lymphocyte-to-monocyte ratio (LMR) were lower in non-remission patients.</p> <p>Spearman correlation identified hypertension, 24-hour urinary protein, and inflammatory indexes as positive correlates with non-remission, while eGFR showed a negative correlation.</p> <p>Multivariate logistic regression confirmed hypertension, high 24-hour urinary protein, SII, SIRI, and PIV as independent risk factors for non-remission; eGFR was a protective factor. Receiver operating characteristic analysis revealed that SII and PIV effectively predicted non-remission (AUC=0.743 and 0.759, respectively). These findings underscore the potential of these indicators in assessing disease severity and guiding personalized treatment strategies.</p> Fangqian Liang Yuyang Yang Yao Sun Lei Xing Xiaolong Yu Junzhi Xia Jingyuan Gao Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20797 Analysis of the Diagnostic Value of Peripheral Blood Indicators for Acute Pyelonephritis and the Influencing Factors of Poor Prognosis https://publish.kne-publishing.com/index.php/IJAAI/article/view/20798 <p>This study explored the diagnostic value of peripheral blood indices for acute pyelonephritis (APN) and the factors influencing poor prognosis.</p> <p>A total of 118 patients with APN admitted to our hospital from January 2022 to June 2024 were retrospectively included as the observation group. Another 62 healthy volunteers were selected as the control group. Clinical data from the two groups were collected, and the diagnostic value of peripheral blood indices for APN was analyzed. The patients were divided according to their prognoses into good-prognosis group and poor-prognosis group, and the influencing factors of poor prognosis were identified by multivariate logistic regression analysis.</p> <p>Compared to the control group, the white blood cell count (WBC) and C-reactive protein (CRP) were higher in the observation group, while <em>IgG</em> and <em>C3</em> were lower. The areas under the curves (AUCs) of WBC, CRP, <em>IgG</em>, and <em>C3</em> in the diagnosis of APN were 0.857, 0.846, 0.902, and 0.893, respectively, and their combined AUC was 0.981. After 3 months of follow-up, there were 43 cases of recurrence (36.44%). The multivariate logistic analysis showed that serum albumin&lt; 35 g/L and a decrease of the IgG level were the influencing factors of poor prognosis in patients with APN.</p> <p>In conclusion, WBC, CRP, <em>IgG</em>, and <em>C3</em> had high value for the diagnosis of APN, and serum albumin&lt; 35 g/L and the decrease of <em>IgG</em> level were the i factors influencing prognosis.</p> <p>&nbsp;</p> Haiyang Qian Danni Zhou Hao Wang Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20798 Integration of Cervical Length, Inflammatory Marker, and Vaginal Biomarkers (PAMG-1 and fFN) in the Diagnosis of Threatened Preterm Labor https://publish.kne-publishing.com/index.php/IJAAI/article/view/20799 <p>The aim of this research was to evaluate the diagnostic efficacy of integrating cervical length (CL), interleukin-6 (IL-6), placental alpha microglobulin-1 (PAMG-1), and fetal fibronectin (fFN) in predicting preterm birth among pregnant women with threatened preterm labor (TPL).</p> <p>This study retrospectively analyzed clinical data from 150 pregnant women admitted for TPL between January 2021 and December 2024. Participants were divided into two groups based on pregnancy outcome: full-term delivery (n=85) and preterm birth (n=65). Additionally, 100 healthy pregnant women with no history of adverse pregnancy outcomes who underwent routine prenatal examinations during the same period were selected as the healthy control group. All participants underwent transvaginal ultrasound to measure CL, and venous blood samples were collected to assess serum IL-6 levels. PAMG-1 and fFN levels were measured in vaginal secretions.</p> <p>There were no significant differences in baseline characteristics among the three groups. However, significant differences in CL, serum IL-6 levels, and positive rates of PAMG-1 and fFN were detected. Pearson correlation analysis showed significant associations between CL, IL-6, PAMG-1, fFN, and preterm birth. ROC curve analysis indicated that the AUC values for CL, IL-6, PAMG-1, and fFN alone were 0.798, 0.803, 0.753, and 0.754, respectively.</p> <p>The combined application of these markers yielded an AUC of 0.920, significantly higher than any single marker. The combined use of CL, IL-6, PAMG-1, and fFN significantly enhances the diagnostic accuracy of preterm birth in patients with TPL.</p> Jianfeng Lu Juefei Lu Xiaoli Zhang Ling Mu Weiming Luo Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20799 The Value of Anti-drug Antibody Detection in Discriminating Patients from Healthy Controls and Predicting the Gross Motor Functional State in Patients with Pompe Disease https://publish.kne-publishing.com/index.php/IJAAI/article/view/20800 <p>Anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody formation is a major challenge in patients with Pompe disease receiving enzyme replacement therapy (ERT). The clinical significance of these antibodies and their detection methods remain uncertain. This study aimed to evaluate the diagnostic and functional relevance of anti-rhGAA antibodies in late- onset Pompe&nbsp;<br>disease (LOPD) and to compare the performance of ELISA and Western blot assays.</p> <p>Fourteen patients with LOPD undergoing ERT and 14 age- and sex-matched healthy controls were studied. Serum anti-rhGAA antibodies and their IgG, IgM, and IgA isotypes were quantified using ELISA and verified by Western blot. Motor function was assessed using the Pompe Motor Function Levels Questionnaire, an adapted version of the GMFCS validated for Pompe disease.</p> <p>Total and isotype-specific anti-rhGAA antibody levels were significantly higher in patients than in controls. ROC analysis showed excellent discrimination between groups. Strong agreement was observed between ELISA and Western blot results. However, antibody levels were not significantly correlated with motor function grade. Given the small sample size (n=14), this non-significant result may reflect limited statistical power rather than a true lack of association.</p> <p>Anti-rhGAA antibody detection effectively distinguishes LOPD patients from healthy individuals. Western blot provides a reliable, low-cost alternative to ELISA, particularly useful in resource-limited settings. Nevertheless, the prognostic utility of antibody titers for functional outcomes remains uncertain and warrants larger, multicenter validation studies.</p> Solmaz Aziz-Ahari Mahdi Aminian Aliasghar Rahimian Shahriar Nafissi Morteza Heidari Ali Rabbani Amir-Hassan Zarnani Ali Mohebbi Reza Shervin Badv Nargess Saladjegheh Sahar Mortezagholi Safdar Masoumi Zahra Hadipour Reza Boostani Mehran Beiraghi Toosi Keyhan Sayadpour Zanjani Ali Khajeh Seyed Hassan Tonkaboni Maryam Sadeghi Farzad Fatehi Elahe Vafaei Mahmoud Reza Ashrafi Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20800 Role of METTL3 Protein in Asthma: Insights from Transcriptomic Profiling and Molecular Docking Analysis https://publish.kne-publishing.com/index.php/IJAAI/article/view/20801 <p>Asthma is a chronic inflammatory disease characterized byimmune dysregulation. This study aimed to perform unbiased analysis of transcriptomic data to identify differentially expressed m6A-related genes in asthma, with a focus on exploring their potential as biomarkers and therapeutic targets.</p> <p>Gene Expression Omnibus (GEO) (GSE134544) dataset was analyzed to identify differentially expressed m6A-related genes. Functional enrichment analysis was performed clusterProfiler, immune infiltration profiling was conducted with CIBERSORT, and a competing endogenous RNA (ceRNA, including microRNA [miR] and lncRNA) network was constructed. Drug enrichment analysis was carried out using DSigDB, and molecular docking was utilized to assess the interaction between dabigatran and the METTL3 protein.</p> <p>From 192 differentially expressed genes, four m6A-related genes (METTL3, HNRNPC, IGFBP2, and RBMX) were identified as the intersecting genes between the m6A-related gene set and differentially expressed genes (DEGs) from the GSE134544 dataset. Gene Ontology (GO) analysis revealed significant enrichment in biological processes related to RNA metabolic processes and post-transcriptional regulation, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified important pathways such as spliceosome and p53 signaling pathways. METTL3 and HNRNPC were central in the ceRNA network, interacting with miRs such as hsa-miR-93-3p and lncRNAs like LINC01529. Drug enrichment analysis identified dabigatran as a potential METTL3 inhibitor, with molecular docking confirming a stable binding affinity (−5.9 kcal/mol).</p> <p>This study emphasizes the critical role of m6A-related genes, particularly METTL3 and HNRNPC, as macromolecules in asthma pathophysiology, and provides insights into their potential as biomarkers and therapeutic targets for asthma treatment.</p> Kaichong Jiang Qiao Li Ling Duan Xieying Zhu Shuang Wu Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20801 Dual Blockade of PD-L1 and AXL: A Novel Immunotherapeutic Approach for Ovarian and Cervical Cancer https://publish.kne-publishing.com/index.php/IJAAI/article/view/20802 <p>Tumor microenvironment modulators have produced durable effects in cancer treatment. Targeting immune checkpoint receptors, such as <em>PD-L1</em>, has demonstrated efficacy in eliciting antitumor responses. However, resistance to immune checkpoint blockers (ICBs) has constrained the efficacy of these therapies. Previous studies showed a link between the expression of <em>AXL</em> receptor tyrosine kinase and resistance to ICBs. Therefore, designing combination treatments with synergistic mechanisms to overcome ICB-based resistance is needed. In addition to antibody-based therapies, gene silencing with siRNAs has recently been explored to alter the cancer environment to enhance the immune response.</p> <p>In this study, we targeted <em>PD-L1</em> using an siRNA and <em>AXL</em> using a blocker (R428) in OVACAR-3 and CaSki cells, ovarian and cervical cancer cell lines, respectively, in the following groups: Scramble-siRNA, PD-L1-siRNA, Scramble-siRNA in conjunction with R428, PD-L1-siRNA in conjunction with R428, R428 monotherapy and untreated controls. Cell viability was assessed by MTT assay after 48 hours of treatment, and cisplatin sensitization was evaluated in resistant OVACAR-3 cells. Gene expression was analyzed by qRT-PCR, while flow cytometry quantified CD44<sup>+</sup>PD-L1<sup>+</sup> populations, apoptosis (Annexin V/PI), and cell cycle distribution.</p> <p>The results showed a significant decrease in cell proliferation, suppression of EMT-regulating genes, reduction of stemness in cancer cells, increased apoptosis and disruption of the cell cycle in the studied cell lines.</p> <p>These findings suggest that simultaneous blockade of <em>PD-L1</em> and <em>AXL</em> could serve as a novel tumor-suppressive strategy, especially for cancer patients resistant to ICBs.</p> Hossein Rahavi Ahmad Najafi Hossein Asgarian-Omran Behrouz Aflatoonian Mohsen Tehrani Ehsan Farashahi-Yazd Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20802 Alterations in Apoptotic Cell Populations, Protein Markers, and Gene Expression Patterns in Rats with Sulfur Mustard-induced Pulmonary Injuries https://publish.kne-publishing.com/index.php/IJAAI/article/view/20803 <p>Sulfur mustard (SM) is a potent chemical warfare agent that causes severe cutaneous, ocular, and pulmonary injuries, with respiratory tract damage being the most life-threatening. Despite its well-documented toxicity, the cellular mechanisms driving SM-induced apoptosis remain poorly understood. This study seeks to elucidate the apoptotic pathways involved in SM-induced pulmonary injury using a rat model.</p> <p>We induced acute lung injury through two delivery methods: intraperitoneal injection (8 mg/kg) and intratracheal instillation (2 mg/kg) of SM, with both doses representing 1 LD<sub>50</sub>. We assessed apoptosis-related proteins and gene expression through TUNEL staining, immunohistochemistry, and quantitative real-time PCR analyses.</p> <p>Intraperitoneal administration of SM resulted in significantly elevated expression of apoptotic markers including annexin A1, annexin A2, cytochrome C, caspase-12, and JNK3, in alveolar epithelial cells compared to intratracheal delivery. Both TUNEL assays and immunohistochemical staining confirmed these findings. These results indicate that intraperitoneal SM exposure triggers more severe apoptotic responses in alveolar epithelial cells than intratracheal exposure at equivalent doses.</p> <p>These findings demonstrate that intraperitoneal models can effectively identify apoptosis-related molecular targets suitable for therapeutic development.</p> <p>&nbsp;</p> Tao Liu Na Zhang Xin Shu Xiaoxuan Hu Jingtong Li Yuxu Zhong Jinyuan Tang Xiao-ji Zhu Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20803 The Coexistence of Asthma and Common Variable Immunodeficiency in a Patient with TNFRSF13B Gene Mutation https://publish.kne-publishing.com/index.php/IJAAI/article/view/20804 <p>Common variable immunodeficiency disorder (CVID) is the most prevalent primary immunodeficiency in adults. Pathogenic mutations of the <em>TNFRSF13B</em> gene were identified in CVID patients and associated with autoimmunity and lymphoproliferation. A study on Swedish children unaffected by CVID has shown that rare variants in the <em>TNFRSF13B</em> gene increase the risk of asthma. To the best of our knowledge, asthma has not been reported in CVID patients with <em>TNFRSF13B</em> gene mutations. We described a patient suffering from asthma and CVID with a heterozygous mutation in the TNFRSF13B gene. According to our findings and previous studies, mutations in the <em>TNFRSF13B</em> gene seem to be possibly associated with the occurrence of asthma in CVID patients.</p> Tayebeh Ranjbarnejad Mansoor Salehi Hassan Abolhassani Roya Sherkat Mohammadreza Sharifi Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20804 Good’s Syndrome Complicated with COVID-19 and Recurrent Pulmonary Infections: A Case Report https://publish.kne-publishing.com/index.php/IJAAI/article/view/20805 <p>Good’s syndrome (GS), a rare immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, presents diagnostic and therapeutic challenges due to recurrent infections.</p> <p>We report a 53-year-old male farmer with GS complicated by recurrent pulmonary infections and COVID-19. Initial management focused on antiviral/anti-infective therapy and corticosteroids, but persistent hypogammaglobulinemia, B-cell depletion, and thymoma history were overlooked.</p> <p>Diagnosis was confirmed upon integrating the thymoma history, immunological profiling, and bronchial alveolar lavage-next generation sequencing, revealing <em>Pneumocystis jirovecii</em> and Herpes Simplex Virus-1 coinfections. Treatment with intravenous immunoglobulin loading dose (2 g/kg), pathogen-targeted therapy (voriconazole, cotrimoxazole), and tapered corticosteroids achieved clinical remission, with immunoglobulin G (IgG) elevating to 6.35 g/L.</p> <p>This case underscores the necessity of a "four-dimensional early warning system" integrating thymoma history, immune, imaging, and pathogen for timely GS diagnosis. Multidisciplinary collaboration and personalized regimens combining immunoglobulin replacement, precision anti-infectives, and immunomodulation are pivotal for optimizing outcomes in GS patients with complex infections.</p> <p>&nbsp;</p> Wenjuan Xia Mengqi Wu Fang He Copyright (c) 2026 Iranian Journal of Allergy, Asthma and Immunology 2026-01-27 2026-01-27 10.18502/ijaai.v25i2.20805