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

{"title":"Eosinophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Allergic Rhinitis.","authors":"Alireza Sharifi, Maryam Sharifi, Elham Farasat, Maryam Yaghoubi Hamgini, Shohreh Norouzi, Selda Zahedi Abdi, Parsa Taghavi, Nadereh Alani, Shahram Seyedi, Mehran Jamali, Mohammad E Ghaffari, Samad Samadizadeh, Brent A Senior, Joseph Z Lebowitz","doi":"10.18502/ijaai.v25is11.22482","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22482","url":null,"abstract":"<p><p>A growing number of literatures explores the diagnostic role of serum eosinophil-to-lymphocyte ratio (ELR) and platelet-to-lymphocyte ratio (PLR) in patients with allergic rhinitis (AR), yielding variable findings and lacking control of potential confounding variables and standardized cut-offs for clinical application. We aim to clarify their role through a systematic review and meta-analysis. Web of Science, PubMed, Embase, Scopus, Cochrane Central Register of Control Trials, Google Scholar, and Medline were systematically searched up to October, 2025. The search strategy was described by a combination of relevant medical subheadings (MeSH) and keywords. Eligible English language studies were reviewed, and their quality was appraised. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 12 studies, including 3 449 individuals, met the inclusion criteria. AR group had significantly higher ELR (SMD: 0.64) and insignificantly lower PLR (SMD-0.02) than control. Patients with persistent AR had, numerically but not significantly, higher ELR (SMD: 1.19) and PLR (SMD: 0.58) compared to intermittent AR. ELR value of greater than 0.085 had a pooled AUC of 67% in discrimination of patients with AR from control. This AUC rate was statistically significant. This review investigated that no clear correlation was found between mean PLR and AR. However, mean ELR was found to be significantly increased in patients with a diagnosis of AR, and a numerical trend toward higher ELR with greater disease severity was observed. Though further research is necessary to determine its clinical utility.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"44-53"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling a Rare Complication: BCG-associated Brain Abscess in Wiskott-aldrich Syndrome.","authors":"Mehrsa Hamidi, Zohreh Habibi, Nima Parvaneh, Mahshid Movahedi","doi":"10.18502/ijaai.v25is11.22499","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22499","url":null,"abstract":"<p><p>Wiskott-aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by thrombocytopenia, eczema, and recurrent infections. Live vaccines, such as Bacillus Calmette-Guérin (BCG), routinely administered in tuberculosis-endemic regions, may cause severe complications in undiagnosed patients. We report a 2-year-old boy with genetically confirmed WAS who developed a rare BCG-related brain abscess. The patient initially presented with neonatal thrombocytopenia and eczema, followed by recurrent respiratory and gastrointestinal infections. Whole exome sequencing identified a pathogenic mutation in the WAS gene. During pre-hematopoietic stem cell transplantation (HSCT) evaluation, brain imaging revealed a large multiloculated right parieto-occipital abscess with significant mass effect. Surgical drainage was performed, and polymerase chain reaction confirmed Mycobacterium bovis (BCG strain). Antitubercular therapy was initiated. Severe thrombocytopenia complicated management and necessitated splenectomy. Although platelet counts improved and infection was partially controlled, HSCT was postponed due to active infection. The patient subsequently died following a severe COVID-19 infection. This case highlights the diagnostic and therapeutic challenges of BCG-related brain abscess in patients with WAS and underscores the importance of early genetic diagnosis, avoidance of live vaccines, and timely definitive treatment in primary immunodeficiencies.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"211-217"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Cell Profiling in Peptic Ulcer Disease: Investigation of MAIT Cells and Key Inflammatory Cytokines IL-17 and IFN-γ.","authors":"Alireza Omidvar-Mehrabadi, Mehdi Shakouri-Khomartash, Hasan Abedi, Mojgan Mohammadi-Mehr, Ali Faridfar, Ali Shakeri-Moghaddam","doi":"10.18502/ijaai.v25is11.22489","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22489","url":null,"abstract":"<p><p>Peptic ulcer disease (PUD) is a common gastrointestinal disorder associated with chronic mucosal inflammation and immune dysregulation. Recent evidence suggests that Mucosal-associated invariant T (MAIT) cells, a subset of T cells expressing CD161 and Vα7.2, are involved in mucosal immunity and inflammatory responses. However, their precise role in PUD remains unclear. Given their dual function in immune defense and inflammation, investigating MAIT cell alterations in PUD could provide novel insights into disease pathogenesis and potential therapeutic targets. A cross-sectional study was performed, including 25 patients with endoscopically verified PUD and 25 healthy controls. Flow cytometry was used to quantify circulating MAIT cells (Vα7.2+CD161++) and their subsets (CD4+, CD8+, and double-negative). Serum interleukin-17 (IL-17) and interferon-γ (IFN-γ) levels were measured using ELISA in 21 PUD patients and 21 healthy controls. Correlations between MAIT cell frequencies and cytokine levels were analyzed using the Spearman correlation coefficient. PUD patients exhibited a substantially elevated frequency of circulating MAIT cells compared to controls. Among subsets, CD8+ MAIT cells showed the most pronounced increase, correlating positively with serum IFN-γ levels (r=0.5819). Furthermore, levels of IL-17 and IFN-γ were substantially elevated in individuals with PUD in comparison to controls. Our results indicate that MAIT cells, particularly the CD8+ subset, may contribute to immune activation in PUD. The observed increase in MAIT cells, along with elevated IL-17 and IFN-γ levels, highlights their potential involvement in disease progression. These findings support the potential role of MAIT cells as biomarkers or therapeutic targets in PUD.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"129-139"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Unexpected Association of a Novel MYOF Variant with Generalized Myopathy and HAE-nl-C1-INH.","authors":"Zahra Alizadeh, Atefe Alirezaee, Laleh Habibi, Abbas Tafakhori, Leila Moradi, Mohammad Reza Fazlollahi, Zahra Pourpak","doi":"10.18502/ijaai.v25is11.22498","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22498","url":null,"abstract":"<p><p>Myoferlin (encoded by MYOF) is a highly expressed protein in myoblasts and endothelial cells; mutations in MYOF are linked to malignancies, skeletal and cardiac myopathy, and hereditary angioedema with normal C1-inhibitor (HAE-nl-C1-INH). We present a 31- year-old female with recurrent severe abdominal angioedema attacks since late childhood. Mucocutaneous angioedema attacks began in early adolescence, triggered by stress and mechanical stimuli, and hormonal changes, often proceded bya fatigue or chest discomfort. Assessment of C1INH level and function had not shown any deficiency C1-INH protein level and function. Because C1-INH protein level and function were normal, whole exome sequencing (WES) was performed, identifying a novel heterozygous missense mutation in MYOF. Family screening revealed the same mutation in her mother and brother. Her angioedema symptomswere partially controlled using daily tranexamic acid and weekly anti-androgenic agents, with fresh frozen plasma or Berinert reserved for severe attacks. Over the past two years, she developed slowly progressive weakness in her facial, proximal, and distal extremity muscles, causing fatigue, bilateral ptosis, and difficulty climbing stairs or rising from a chair. Neurological examination, EMG-NCV studies, and elevated serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels confirmed reduced muscle strength and generalized myopathy. Additionally, she experienced palpitations and unprovoked sinus tachycardia, likely reflecting cardymyopathy secondary to myoferlin deficiency.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"205-210"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-inducible Factor 1-α: A Key Regulator of Immune Checkpoint Receptors in Acute Myeloid Leukemia Cell Lines.","authors":"Amir Kahrizi, Armin Akbar, Ahmad Najafi, Hossein Asgarian-Omran, Reza Valadan, Mohammad Mehri, Mohsen Tehrani","doi":"10.18502/ijaai.v25is11.22493","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22493","url":null,"abstract":"<p><p>The Warburg effect is one of the most important metabolic alterations in tumor cells. Hypoxia-inducible factor 1-alpha (HIF-1α) targets a broad range of gene promoters in normoxic and hypoxic conditions in cancers. Herein, we investigate the effects of HIF-1α inhibition on cell viability and messenger RNA (mRNA) expression of immune checkpoint receptors (ICRs) in acute myeloid leukemia cell lines. K-562 and HL-60 cells were treated with silibinin as an HIF-1α inhibitor. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by quantification of V-domain immunoglobulin suppressor of T-cell activation (VISTA), T-cell immunoglobulin and mucin domain 3 (TIM3), and Galectin-9 mRNA expression via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expression levels of VISTA, TIM3, and Galectin-9 decreased after silibinin treatment within both K-562 and HL-60 cells; however, there were some disparities in gene expression levels between the two cell lines. VISTA and TIM3 expression were reduced by approximately 70% in K-562 at the 40% inhibitory concentration (IC40), while no significant changes were observed in HL-60 cells. Conversely, Galectin-9 expression was decreased significantly at both the IC30 and IC40 in HL-60, whereas it was almost consistent in K-562 cells.  Collectively, we have shown that silibinin could serve as a cytotoxic small-molecule inhibitor and regulate the expression of ICRs, potentially counteracting T-cell exhaustion.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"175-181"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rheumatic Manifestations in Patients with Combined Immunodeficiency.","authors":"Leila Ghasemi Hashtrodi, Zahra Chavoshzadeh, Mehrnaz Mesdaghi, Narges Eslami, Golnaz Eslamian, Mehdi Alizadeh, Leily Sokoty, Shahrzad Fallah, Maryam Asarehzadegan Dezfouli, Maryam Heydarazad Zadeh, Shabnam Hajiani Ghotbabadi, Hedieh Haji Khodavardi Khani, Nima Parvaneh, Reza Sinaee, Azadeh Zeinab Mirzaee, Nima Rezaei, Samin Sharafian, Reza Shiari","doi":"10.18502/ijaai.v25is11.22487","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22487","url":null,"abstract":"<p><p>Combined immunodeficiencies (CIDs) represent a rare group of inherited immune disorders in which defects in T- and B-lymphocyte function lead to recurrent infections, immune dysregulation, and an increased tendency toward autoimmune and rheumatologic complications. A retrospective cross-sectional analysis was performed on 150 patients with CID, diagnosed according to the European Society for Immunodeficiencies (ESID) criteria and followed at the Children's Medical Center and Mofid Children's Hospital (Tehran, Iran) between 2009 and 2020. Clinical records, immunologic evaluations, and rheumatologic findings were reviewed, with particular attention to autoantibody detection and disease frequency. Among 150 patients, 42 (28%) exhibited rheumatologic manifestations, with a higher frequency in females. Undifferentiated rheumatoid arthritis, undifferentiated juvenile idiopathic arthritis, and Kawasaki disease were the predominant conditions. Although lower lymphocyte counts and immunoglobulin levels were observed among non-rheumatologic patients, the differences were not statistically significant. Impairments in T-cell-mediated immunity and antibody synthesis among individuals with CID hinder the recognition of autoantibody-associated rheumatologic disorders and delay diagnosis. Moreover, these conditions often present atypically in immunocompromised hosts; therefore, a vigilant clinical approach is essential for early identification and management.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"103-111"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Inflammatory Benefits of Nebulized Furosemide with Salbutamol-Ipratropium in COPD Exacerbations: A Randomized Controlled Trial.","authors":"Mahdi Behi, Babak Gholamine, Mohammad Reza Masjedi, Alireza Eslaminejad, Esmaeil Idani, Mohsen Sadeghi, Akram Qanavati, Sayed Mehran Marashian, Esmaeil Mortaz, Atefeh Abedini, Mihan Pourabdollah, Bita Pakshad, Saeid Mahmoodian","doi":"10.18502/ijaai.v25is11.22488","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22488","url":null,"abstract":"<p><p>Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of morbidity, mortality, and healthcare burden. While standard bronchodilator therapy alleviates airway obstruction, its efficacy is often limited. This study evaluated nebulized furosemide, which has bronchodilatory and anti-inflammatory effects, as an adjunct to salbutamol-ipratropium in hospitalized COPD patients. Ninety‑two patients with exacerbated COPD were randomly assigned to two equal groups (46 each). The intervention group received nebulized salbutamol-ipratropium plus furosemide (20 mg), and the control group received salbutamol-ipratropium, both every 8 hours for 10 minutes over 5 consecutive days. Demographic and clinical variables, pulmonary function indices (FEV1, FVC, FEV1/FVC), clinical outcomes (COPD Assessment Test (CAT), Modified Medical Research Council (mMRC)scores, and quality of life by St. George's Respiratory Questionnaire (SGRQ)), arterial blood gases, and inflammatory biomarkers (TNF-α, IL-6, IL-8, CRP, ESR, neutrophil %, WBC) were measured before and after treatment. Demographic characteristics and baseline indices did not differ significantly between the groups. Dyspnea and respiratory symptoms (mMRC and CAT scores) decreased significantly, while quality of life, improved markedly in the intervention group compared to the control group. Pulmonary function also showed significant enhancement, with the FEV₁/FVC ratio increasing. Arterial blood gas analysis showed higher PaO₂ and lower PaCO₂ in the intervention group. IL-6 and IL-8 decreased significantly, and no adverse events were reported. Nebulized furosemide enhances standard therapy in COPD exacerbations, improving lung function, relieving symptoms, and reducing systemic inflammation. Its safety, accessibility, and low cost make it a promising adjunct treatment.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"112-128"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine Expression and Promoter Methylation Signatures Underlying Immune Dysregulation in Mild and Severe COPD.","authors":"Amirhossein Faghih Ojaroodi, Neda Gholamzadeh, Khadijeh Pouya, Sanaz Abbaspour-Aghdam, Haleh Mikaeili, Armin Sadeghi, Majid Ahmadi, Mehdi Nadiri","doi":"10.18502/ijaai.v25is11.22485","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22485","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung condition and a leading cause of morbidity and mortality worldwide. Despite well-established links to smoking, emerging evidence highlights the involvement of complex immune and epigenetic mechanisms in its pathogenesis. This study aimed to investigate the expression, secretion, and promoter methylation status of key pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with mild and severe COPD, compared with healthy individuals. PBMCs were isolated from 90 participants divided into three groups: severe COPD, mild COPD, and healthy controls. Quantitative polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and methylation-specific PCR were employed to evaluate gene expression, protein secretion, and promoter methylation of inflammatory cytokines. Patients with COPD exhibited significant upregulation of pro-inflammatory cytokines (Interleukin1β (IL-1β), IL-6, IL-18, IFN-γ, and TNF-α) at both transcript and protein levels, with more pronounced alterations in the severe group. Conversely, anti-inflammatory mediators (IL-10 and TGF-β) were significantly downregulated. Promoter methylation analysis revealed hypomethylation in pro-inflammatory cytokine genes and hypermethylation in anti-inflammatory ones, correlating with disease severity. The findings demonstrate that COPD progression is associated with a shift toward a hyper-inflammatory, hypo-regulatory immune phenotype sustained by epigenetic modifications. These results support the potential for integrating cytokine-methylation signatures into clinical staging and for targeting epigenetic and immune pathways in future therapeutic strategies.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"78-87"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Regulatory B10 Cells in Common Variable Immunodeficiency Patients with and without Autoimmunity.","authors":"Pouria Ghiaee, Sarehsadat Ebrahimi, Seyed Alireza Mahdaviani, Fatemeh Tarighat Monfared, Marzieh Tavakol, Mehrdad Dargahi Mal-Amir, Nima Rezaei, Abdollah Jafarzadeh","doi":"10.18502/ijaai.v25is11.22491","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22491","url":null,"abstract":"<p><p>Common variable immunodeficiency disease (CVID) is the most prevalent symptomatic inborn errors of immunity, determined by defective B cell function, impaired antibody production, and susceptibility to frequent respiratory infections, enteropathy, autoimmunity, and malignancy. Due to the importance of autoimmunity in CVID and the probable role of regulatory B lymphocytes, we aimed to determine the frequency of B10 cells in CVID patients with and without autoimmunity. A total of 24 CVID patients and 12 healthy controls were enrolled in the study. Patients were divided into two equal groups, with and without autoimmunity. Peripheral blood cells were stained with monoclonal antibodies (mAbs) to identify CD24hiCD38hi B cells, CD27int CD38+ (plasmablasts), and CD24hiCD27+ B cells by flow cytometry. The percentages of B10, CD24hiCD27+ and CD27int CD38+ cells were significantly lower in total CVID patients, CVID patients with autoimmunity and CVID patients without autoimmunity compared to healthy controls (mean±standard deviation (SD) percentage of B10 cells: 6.36±9.21(total CVID), 2.81±5.00 (CVID with autoimmunity), and 3.25±3.5 (CVID without autoimmunity) vs. 13.02±12.45 (healthy controls); CD24hiCD27+ cells: 2.39±3.89, 3±5.20 and 1.78±1.94 vs. 20.38±14.27; CD27int CD38+ cells: 6.80±18.49, 7.40±20.24 and 6.20±17.45 vs. 11.84±5.71). CVID patients without autoimmunity had a higher percentage of CD24hiCD38hi cells than CVID patients with autoimmunity (4.73±4.14 vs. 2.62±5.02). The defect of regulatory B cells plays a significant role in the pathogenesis of autoimmunity in CVID. Further multicenter studies with higher sample sizes are suggested to determine the role of Breg cells in the clinical course of autoimmunity.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"152-164"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Recurrent Infections: Immune Dysregulation Manifestations, Genotype-phenotype Heterogeneity, and Three Novel BTK Variants in X-linked Agammaglobulinemia.","authors":"Ozan Kapçay, Aşkın Şen, Filiz Demir Şahin, Mehmet Kılıç","doi":"10.18502/ijaai.v25is11.22497","DOIUrl":"https://doi.org/10.18502/ijaai.v25is11.22497","url":null,"abstract":"<p><p>X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by BTK gene mutations, characterized by hypogammaglobulinemia and recurrent infections. This study evaluates a long-term pediatric cohort to assess clinical spectrum, therapeutic outcomes, and molecular findings. We retrospectively reviewed clinical, immunological, treatment, and genetic data for 11 male XLA patients followed over 20 years at our center. Median age at symptom onset was 12.7 months (range: 3-60), while median age at diagnosis was 4.5 years (range: 1-10), revealing marked diagnostic delays in patients without family history. Severe complications included bronchiectasis, septic arthritis, and immune dysregulation (e.g., juvenile idiopathic arthritis, autoimmune hepatitis, pancytopenia, celiac disease). Immunoglobulin replacement and antibiotic prophylaxis significantly reduced median annual infections from 16.9 to 2.09. Six distinct BTK variants were identified, including three novel mutations: c.90del, c.1922_1924delGTC, and c.1589dup. Inter-sibling phenotypic heterogeneity was notable. In the absence of functional expression studies, pathogenic contributions of novel variants remain exploratory. XLA extends beyond recurrent infections to encompass significant immune dysregulation and phenotypic variability. Early diagnosis, family screening, genetic testing, and tailored immunoglobulin therapy are vital to improve long-term outcomes. Larger multicenter cohorts with functional testing are needed to validate genotype-phenotype associations.</p>","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"25 Sup 11","pages":"191-204"},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}