Anaphylaxis is a severe, rapidly progressing, and potentially life-threatening emergency requiring prompt, evidence-based intervention. This study assessed pre-hospital emergency healthcare professionals’ knowledge of anaphylaxis diagnosis, acute management, and treatment protocols in line with current clinical guidelines. A descriptive cross-sectional study was conducted between February and April 2025 among physicians, paramedics, and emergency medical technicians (EMTs) working in Emergency Medical Services (EMS) stations. Data were collected via a 21-item Google Forms survey covering demographics and key knowledge domains based on established pediatric anaphylaxis guidelines. A total of 322 professionals participated: paramedics (n=214, 66.5%), EMTs (n=73, 22.7%), and physicians (n=35, 10.9%). Although most reported prior anaphylaxis training (90.0%) and clinical encounters (87.6%), only 52.2% correctly identified all three diagnostic criteria. Regarding pharmacologic management, 81.7% recognized epinephrine as first-line treatment, with physicians performing best (94.3%) compared to paramedics (81.8%) and EMTs (75.3%). Similarly, 81.1% correctly identified the intramuscular route, with physicians again demonstrating superior knowledge (95.5%). However, major deficiencies were noted in appropriate patient positioning (52.2%) and epinephrine auto-injector use (50.6%), with significant inter-professional differences across both domains. Substantial knowledge gaps exist among pre-hospital emergency providers regarding anaphylaxis diagnosis, patient positioning, and auto-injector administration. Targeted training and standardized protocols are urgently needed to enhance competency and improve patient safety in pre-hospital anaphylaxis management.
Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that can progress to cirrhosis and liver failure if untreated. Current therapies, mainly corticosteroids, are effective but limited by adverse effects and incomplete responses, prompting the search for safer alternatives. Peiminine, an alkaloid derived from Fritillaria species, has demonstrated anti-inflammatory and antioxidant properties in several disease models. This study evaluated its efficacy in a concanavalin A (ConA)–induced mouse model of AIH. Male C57BL/6 mice were divided into six groups, including ConA-injured animals, and treatment groups receiving peiminine (3 mg/kg, i.p.), prednisolone (10 mg/kg, i.p.), or their combination. ConA injection caused sharp increases in ALT (↑ 5.4-fold), AST (↑ 4.8-fold), and ALP (↑ 3.9-fold), alongside marked elevations in MPO activity, nitric oxide, and pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ). Peiminine significantly reversed these alterations-reducing ALT, AST, and ALP by 65% to 75% and restoring IL-4, TGF-β, and SOD activity toward normal values. Pre-treatment provided stronger protection than post-treatment, and outcomes were comparable to those of prednisolone, with combination therapy yielding the greatest improvement across all indices. These findings indicate that peiminine mitigates immune-mediated hepatic injury by modulating cytokines, reducing oxidative stress, and maintaining liver integrity. Peiminine may represent a promising preventive or adjunct therapy for AIH, warranting further mechanistic and long-term investigations.
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.
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.
Cyclin-dependent kinase 9 (CDK9), the kinase associated with positive transcription elongation factor b (P-TEFb), enhances transcription elongation by phosphorylating RNA polymerase II and transcription elongation factors. The critical function of P-TEFb is in mediating networks of transcription that are induced by cytokines. More specifically, P-TEFb is involved in STAT3 signaling induced by IL-6 and TNF-inducible NF-κB activation. Within these signaling cascades, the pathways become hyperactivated due to abnormal CDK9 activity, which in turn increases inflammation and causes tissue damage. Pharmacological research has recently made great strides, and new CDK9 inhibitors are being considered as potential treatment options for regulating abnormal inflammatory responses. The efficacy of these inhibitors in reducing inflammation and symptom severity has been demonstrated in preclinical studies of inflammatory diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, and atherosclerosis. The advancement of next-generation CDK9 inhibitors with improved selectivity and diminished off-target effects provides considerable promise for the treatment of many inflammatory disorders.
The management of treatment strategies in COVID-19 is critical, especially in patients with type 2 diabetes. Non-enzymatic glycation of transmembrane protease serine 2 and angiotensin-converting enzyme 2 during COVID-19 in patients with diabetes may exacerbate immune dysregulation and inflammation. Elevated inflammatory cytokines such as IL-1, IL-2, IL-6, IL-7, and IL-10, tumor necrosis factor-α, interferon-γ, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1 have been observed in COVID-19 patients. This review aims to assess the relationship between inflammatory markers, including C-reactive protein, and micronutrients (vitamins D and C, zinc, and copper) with the severity of COVID-19 infection in patients with type 2 diabetes. A narrative review was conducted through a comprehensive literature search of English-language articles published between 2000 and 2025. The databases searched included PubMed, Scopus, the ISI Web of Science, Cochrane, and Embase. Search terms included COVID-19, infections, type 2 diabetes mellitus, interleukins, and micronutrients. English-language scientific articles, systematic reviews, and meta-analyses were included, while studies lacking sufficient information, letters, comments, and editorials were excluded. Evidence suggests that immune-boosting components such as proteins, vitamins, and minerals can enhance immunity to infections. Vitamins D and C, zinc, and copper play supportive roles in immune function, potentially modulating the inflammatory response in COVID-19 patients with type 2 diabetes. High levels of inflammatory cytokines correlate with increased disease severity in this population. Understanding the interplay between inflammatory markers and micronutrients may guide improved therapeutic strategies for managing COVID-19 in diabetic patients. Further research is warranted to clarify these relationships and optimize clinical outcomes.
Osteoarthritis (OA) is the most common form of arthritis, characterized by pathological changes in joint components. Increasing evidence suggests that helper T (TH) lymphocytes play a pivotal role in the inflammatory processes associated with OA. Curcumin, the primary polyphenolic compound found in Curcuma longa, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of curcumin on the gene expression of key transcription factors of TH1 and TH2 cells and to explore their associations with clinical and immunological parameters in patients with knee OA. This mechanistic sub-study presents a secondary molecular analysis of RNA biospecimens from a previously completed double-blind, placebo-controlled clinical trial involving 30 patients with knee OA. Participants were randomly assigned to receive either 80 mg/day of nano-micelle curcumin or a placebo for 3 months. Expression levels of T-box transcription factor 21 (T-bet) and GATA binding protein 3 (GATA3), the key transcription factors of TH1 and TH2 cells, respectively, were quantified using SYBR Green-based real-time PCR. Their associations with changes in visual analogue scale (VAS) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and percentages of CD4+ and CD8+ T cells were analyzed. Curcumin administration significantly reduced T-bet gene expression compared to baseline and showed a positive correlation with the frequency of CD8+ T cells, while GATA3 expression remained unchanged. These findings may provide a novel molecular perspective on curcumin's potential to influence CD8+ T cell dynamics by modulating TH1-associated transcriptional programs.
SARS-CoV-2 infection causes significant acute and long-term morbidity, including persistent pulmonary and muscular dysfunction in athletes. Physical exercise alters circulating microRNA (miR) profiles, and specific microRNAs have documented roles in inflammation, immune regulation, muscle metabolism, and regeneration. This study characterizes circulating microRNAs relevant to COVID-19 pathogenesis and post-viral recovery, including miR-155, miR-146a, the let-7 family, miR-21, miR-424, miR-1, miR-133, miR-499, miR-208, miR-486, and miR-22, and examines how different exercise modalities may modulate these microRNAs to support pulmonary and muscular function in post-COVID-19 athletes. miR-155 and miR-146a are highlighted as modulators of innate and adaptive inflammatory signaling and as mediators of cytokine responses implicated in severe COVID-19. Moreover, several microRNAs, such as miR-21, miR-155, miR-146a, and the let-7 family, converge on NF-κB and related pathways, linking altered miR expression to immune dysregulation and cytokine-driven tissue injury. Additionally, muscle-enriched and metabolism-associated microRNAs regulate myogenesis, mitochondrial biogenesis, and key metabolic pathways (PGC-1α, AMPK, mTOR)-processes essential for muscle repair, endurance recovery, and respiratory muscle support after SARS-CoV-2 infection. Different types of exercise produce distinct miR signatures; notably, moderate-intensity exercise consistently promotes anti-inflammatory and pro-repair miR patterns. We emphasize the therapeutic potential of moderate-intensity exercise as a non-pharmacological strategy to regulate miR expression, reduce cytokine-mediated damage, and support functional recovery in post-COVID-19 athletes. To our knowledge, this is the first study to link exercise-driven miR changes with functional pulmonary and muscular recovery in athletic populations recovering from COVID-19, supporting moderate-intensity exercise as a promising strategy for rehabilitation and performance restoration.
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.
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 lead to delay diagnosis. Moreover, these conditions often present atypically in immunocompromised hosts; therefore, a vigilant clinical approach is essential for early identification and management.
Long COVID syndrome (LCS) is characterized by persistent multi-system manifestations with an unclear underlying pathophysiology. Identifying the genetic and immunological factors associated with LCS is essential for improved risk stratification and clinical management. This study investigated whether incorporating HLA-DRB1* and HLA-DQB1* genotyping data could enhance the predictive value of laboratory parameters for identifying individuals at higher risk of developing LCS. Demographic characteristics and relevant clinical history data were extracted from the medical records of 88 individuals diagnosed with LCS (LCS+) and 96 individuals without LCS (LCS−). Serum levels of anti-receptor binding domain IgG (anti-RBD IgG), anti-β2-glycoprotein I IgG (anti-β2GPI IgG), and C-reactive protein (CRP) were measured. Low-resolution genotyping was performed to identify HLA-DRB1* and HLA-DQB1* alleles. Logistic regression analysis was employed to examine the associations between HLA alleles and LCS status. Subsequently, mediation analysis was conducted to explore the potential mechanistic roles of anti-RBD IgG, CRP, and anti-β2GPI IgG in these observed relationships. The LCS+ group exhibited a significantly higher frequency of the HLA-DRB1*01 allele and a lower frequency of the HLA-DRB1*11 than the LCS− cohort. Serum levels of both CRP and anti-β2GPI IgG were substantially higher in the LCS+ cohort, whereas anti-RBD IgG levels were significantly lower. After adjusting for key variables, HLA-DRB1*01 and HLA-DRB1*11 remained significantly associated with LCS. Mediation analysis suggested that these HLA associations might be partially mediated by CRP, anti-RBD IgG, and anti-β2GPI IgG levels. Our findings indicate that the combination of HLA-DRB1*01 and HLA-DRB1*11 allele screening with serological profiling (anti-RBD IgG, CRP, and anti-β2GPI IgG) may contribute to refining predictive models of LCS susceptibility, though clinical utility requires validation in larger, independent cohorts.
Chemokines and their receptors play a central role in mediating the migration of pathogenic T cells into the central nervous system of patients with multiple sclerosis (MS). Vitamin D and curcumin are known to possess anti-inflammatory and immunomodulatory properties; however, their combined effects on T-cell chemokine receptor expression in MS remain poorly defined. In this study, we investigated the in vitro effects of vitamin D, curcumin, and their combination on CD4+ and CD8+ T cells expressing CXCR3, CCR6, and CCR4 in patients with relapsing-remitting MS (RRMS). Peripheral blood mononuclear cells were collected from patients in relapse (n=10), remission (n=14), and healthy controls (n=15) and analyzed using flow cytometry. Relapse patients exhibited elevated frequencies of CXCR3+CD4+ T cells compared to healthy controls, which normalized following treatment. Increased CCR6+CD4+ T cells and CXCR3+CD8+ T cells were also observed in patients, with a significant reduction achieved only after combined treatment with vitamin D and curcumin. The combined treatment further decreased the mean fluorescence intensity of CXCR3 and CCR6 on T cells in relapse patients, while vitamin D alone specifically reduced CCR4+CCR6+CD4+ T cells, a TH17-like subset enriched during relapse. These findings indicate that vitamin D and curcumin, particularly in combination, modulate T-cell activity by downregulating chemokine receptor expression and may represent a promising adjunctive approach for controlling immune cell migration in MS.
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
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.
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.
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.
Eosinophilic gastrointestinal diseases (EGIDs) are chronic, TH2-mediated conditions. Eosinophilic esophagitis (EoE) is the most common type, while non-EoE EGIDs affect other gut segments. This retrospective study of 111 patients (50 EoE and 61 non-EoE) from 2011 to 2022 compared the clinical aspects of these 2 types. Dysphagia and food impaction dominated in EoE, while abdominal pain, nausea, and diarrhea were more common in non-EoE EGIDs. Atopic comorbidities were frequent. Diagnostic delays>1 year were more common in EoE (72% vs 47.5%). The overall clinical response rate was 88.29%, with most patients using food avoidance (90.99%) and proton pump inhibitors (94.59%). Clinical relapses occurred in 38.88% over the mean follow-up of 4.62 years and were unaffected by therapy type. Failure to thrive was seen in 26.7%, with no significant intergroup difference. This study highlights a prolonged diagnostic delay in EoE vs non-EoE EGIDs. Both groups showed similar, favorable response rates, underscoring a need for greater awareness. Prospective studies with standardized measures are required to optimize management.
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.
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 symptoms were partially controlled using daily tranexamic acid and weekly anti-androgenic agents, while 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.
