Allergologia et immunopathologia最新文献

Background: Bronchial asthma (BA) frequently coexists with obstructive sleep apnea syndrome (OSAS). The obesity-inflammation axis may underlie this overlap, but pragmatic predictors and biomarker utility remain incompletely defined.

Objective: To identify clinical predictors of OSAS in BA and evaluate the diagnostic performance of leptin (LEP), interleukin-6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR), individually and in combination.

Materials and methods: In a prospective study, 263 adults with BA were enrolled and classified into OSAS (n=124) and non-OSAS (n=139) groups by polysomnography. The OSAS group was stratified by apnea-hypopnea index (AHI) into mild (n=59), moderate (n=42), and severe (n=23). Clinical variables were compared with univariate tests. Independent predictors were identified using binary logistic regression. Serum LEP and IL-6 (immunoassays) and NLR (hematology) were measured. Biomarker-AHI relationships were assessed by Spearman's correlation. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves and DeLong's test.

Results: On univariate analysis, OSAS cases were older and more often male, with higher rates of obesity, severe BA, neck circumference >40 cm, rhinitis, and gastroesophageal reflux disease (GERD). Logistic regression confirmed obesity, severe BA, neck circumference >40 cm, rhinitis, and GERD as independent predictors. LEP, IL-6, and NLR were significantly higher in OSAS than non-OSAS and increased progressively across AHI strata. LEP correlated strongly with IL-6, IL-6 with NLR, and LEP with NLR to a lesser extent (all P<0.001). For diagnosing BA-OSAS, AUCs were 0.746 (LEP), 0.771 (IL-6), 0.742 (NLR), and 0.826 for their combination, which outperformed individual markers (DeLong, P<0.05).

Conclusion: Obesity, neck circumference >40 cm, severe BA, rhinitis, and GERD independently predict OSAS in BA. LEP, IL-6, and NLR correlate with OSAS severity, and their combined use provides superior diagnostic value for identifying BA-OSAS comorbidity and may aid targeted screening and referral. (≈240 words).

Background: In southern Europe, allergy to Alternaria alternata (A. alternata) and Olea europaea (O. europaea) pollen are prevalent, significantly contributing to allergic conditions like asthma and rhinitis. This study investigates the effectiveness and safety of immunotherapy in pediatric patients utilizing a glutaraldehyde-polymerized allergen extract mixture of A. alternata and O. europaea.

Methods: This real-world, retrospective, observational study included pediatric patients diagnosed with rhinitis with or without asthma, co-sensitized to A. alternata and O. europaea. Patients received immunotherapy with a mixture of individually polymerized allergen extracts of A. alternata and O. europaea, each at a concentration of 10,000 TU/mL. Effectiveness was assessed by comparing rhinitis and asthma severity and medication requirements before and after at least 6 months of treatment. Safety was evaluated by documenting local and systemic adverse reactions.

Results: A total of 49 patients were included, with a median treatment duration of 9 months. Prior to treatment, 84% (41/49) of patients had moderate-severe rhinitis, which significantly decreased to 49% (24/49) posttreatment (p=0.001). Asthma severity also improved considerably, with the proportion of patients experiencing intermittent-mild asthma rising from 8% pretreatment to 61% posttreatment. The use of medication for both rhinitis and asthma also declined. Out of 424 injections, only two local reactions were reported (0.47%), with no systemic reactions.

Conclusion: Immunotherapy using a mixture of glutaraldehyde-polymerized A. alternata and O. europaea extract is both safe and effective in reducing the severity of rhinitis and asthma in children. This treatment exhibits a high safety profile, with a very low incidence of adverse reactions, making it a promising therapeutic option for pediatric patients with coexisting sensitivities to these common allergens.

Background: Primary immunodeficiency diseases (PIDs) are an expanding group of rarely observed immune system disorders. Various clinical conditions, such as autoimmunity, immune dysregulation, and inflammation, could affect multiple organ systems in PID patients. The heart may be one of these organs; however, studies on this topic are rare. Atrial fibrillation (AF) is a significant cause of mortality and morbidity in the community and an increased P-wave dispersion (PWD) and atrial electromechanical delay (AED) are well-known markers indicating a predisposition to AF. We aimed to determine whether AED and/or increased PWD predict the early risk of AF in PID patients.

Methods: This single-center, prospective controlled study included 61 PID and 60 control group patients. All participants underwent resting electrocardiography, echocardiography, and atrial electromechanical conduction time (AECT) monitoring using tissue Doppler imaging evaluated by an experienced cardiologist.

Results: The PID group had a statistically significantly higher Pmax, Pmin, and PWD values, compared to the control group (102 [92-108] vs. 88 [82-99] ms, P < 0.001; 74 [70-80] vs. 68 [62-72] ms, P < 0.001; 26 [22-30] vs. 21 [18-26] ms, P = 0.001, respectively). Right atrial delay and interatrial delay were discovered to be statistically significantly higher in PID group (4 [2-6] vs. 2 [2-4] ms, P < 0.001; 6 [4-8] vs. 4 [4-6] ms, P = 0.039, respectively). Left atrial delay was also discovered to be high in the PID group, although this difference was not statistically significant (6 [4-6] vs. 4 [3-6] ms; P = 0.05).

Conclusion: We demonstrated that the well-known predictors of AF, AECT, and PWD were increased in PID patients. This result aids in the follow up and survival of PID patients, who experience multiple complications, by enabling the early identification of AF-related mortality and morbidity risk.

Curcumin, a flavonoid derived from turmeric, has demonstrated antioxidant, anti-inflammatory, and anti-allergic effects. This study evaluated the therapeutic efficacy of intranasal curcumin in an allergic rhinitis (AR) rat model. Forty rats were randomized into five groups: a Sham control, an AR model with no treatment (negative control), an AR model treated with intranasal mometasone furoate (positive control), and an AR model treated with intranasal curcumin. Allergic symptoms (sneezing, itching, nasal discharge) were evaluated by both unblinded and blinded observers. Serum ovalbumin (OVA)-specific IgE levels were measured using ELISA. Nasal mucosal histopathology (edema, cilia loss, goblet cell hyperplasia, inflammation, eosinophilia) was assessed by light microscopy. Intranasal curcumin significantly improved histopathological findings and reduced allergic symptoms, with efficacy comparable to steroid treatment. Intranasal curcumin alleviated allergic rhinitis symptoms and inflammation, suggesting a promising, low-cost alternative for AR management.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common culprits of drug hypersensitivity. Previous classifications, including the European Academy of Allergy and Clinical Immunology (EAACI) and the European Network for Drug Allergy framework, left a subset of patients unclassified under the "blended" category, particularly those with anaphylaxis not fitting into standard groups. The World Allergy Organization (WAO) 2025 guidelines introduced new subcategories, such as mixed NSAID-exacerbated cutaneous disease (NECD) and mixed NSAID-exacerbated respiratory disease (NERD) to address this gap.

Objective: To evaluate how patients with reliable histories of NSAID hypersensitivity were reclassified under the WAO 2025 system, and to determine whether the new categories address the limitations of the previous framework.

Methods: We retrospectively analyzed 527 patients with cross-reactive NSAID hypersensitivity confirmed by clinical history and/or aspirin provocation testing at a tertiary allergy center. Patients were classified according to both EAACI 2019 and WAO 2025 guidelines. Demographics, comorbidities (asthma, rhinitis, urticaria, and nasal polyps), laboratory findings (immunoglobulin E, eosinophils, and tryptase), and provocation test outcomes with alternative NSAIDs were evaluated. Statistical analyses included Chi-square/Fisher's Exact tests and logistic regression.

Results: According to EAACI 2019, patients were classified as NECD (n = 228, 43.3%), NERD (n = 27, 5.1%), NSAID-induced urticaria/angioedema (NIUA) (n = 165, 31.3%), single NSAID-induced urticaria/angioedema/anaphylaxis (SNIUAA) (n = 55, 10.4%), and blended (n = 53, 10.1%). Using WAO 2025 guidelines, the blended category was eliminated and redistributed: NIUA increased to 197 (37.4%), mixed NECD (n = 7, 1.3%), and mixed NERD (n = 13, 2.5%) were newly defined. Other groups (NECD, NERD, SNIUAA) remained unchanged. Provocation testing confirmed high tolerability to paracetamol (97.8%), nimesulid (96.1%), meloxicam (94.1%), and celecoxib (92.2%), while aspirin challenge had the highest positivity (22.2%). Atopy was significantly associated with salicylate reactions (p = 0.048), and male gender with salicylate hypersensitivity (p = 0.0087).

Conclusion: The WAO 2025 classification successfully reallocated previously blended cases, particularly into NIUA, mixed NECD, and mixed NERD, thereby improving diagnostic clarity. This updated framework reduces ambiguity and may enhance patient management by better reflecting clinical heterogeneity.

Background: Cutaneous infections caused by dermatophytes and non-dermatophytes fungi have become significant public health and veterinary concern.

Objective: The current study deals with the distribution, characterization, and antifungal susceptibility profile of these fungi.

Materials and methods: A total of 40 sample were screened by KOH mount; positive samples were cultured on SDA. Purified isolates were identified by macroscopic and microscopic characters. Molecular characterization by PCR and sanger sequencing of ITS region confirmed the fungi. Evolutionary trees were constructed using MEGA 11. Different treatment options were evaluated, including amphotericin B, nystatin, fluconazole, itraconazole, and essential oil of Nigella sativa. Initially molecular docking was performed against selected fungal targets (5eqb and 5v5z) using molecular-operating environment (MOE v.2018.01) and Maestro modeling interface 12.3. In vitro antimycotic activity was performed by agar disc diffusion, followed by micro-broth dilution method.

Results: KOH mount revealed that 65% (13/20) samples positive for fungal components. Culture positivity for samples was 23.07% for dermatophytes and 76.92% for non-dermatophytes. Dermatophytes were detected in skin samples. However, non-dermatophytes were isolated from all types of samples. Sequence analysis confirmed the distribution of Arthroderma multifidum, Aspergillus sydowii, and Aspergillus sublatus. In-silico analysis revealed itraconazole as the most effective antimycotic agent with -7.93 kcal/mol (5eqb) and -10.89 (5v5z) kcal/mol. In vitro analysis strengthens docking analysis, itraconazole was the most effective agent with the highest mean ZOI against A. multifidum (72.00±3.46 mm), A. sydowii (62.00±3.00 mm), and A. sublatus (64.00±1.73 mm). Moreover, essential oil of N. sativa was the most effective antifungal against A. sydowii (ZOI; 31.00±3.46 mm, MIC; 3.125±0.00 mg/mL).

Conclusion: The current study is the first report of A. sydowii and A. sublatus in onychomycosis and hair infections in Pakistan. This study provides awareness about the existence of new fungal pathogens and highlights the availability of effective treatment options for emerging fungal infections.

Background: Ankylosing spondylitis (AS), a long-term autoimmune disorder characterized by systemic inflammation, manifests as gradually worsening arthritis predominantly affecting the spinal column and sacroiliac joints. While emerging biologic agents have broadened treatment possibilities, their clinical application raises notable safety considerations.

Objective: To comprehensively summarize recent advancements in bDMARD applications (including tumor necrosis factor-alpha inhibitors (TNFi), interleukin 17 inhibitors (IL17i), and Janus kinase inhibitors (JAKi)) for AS management.

Material and methods: A thorough bibliographic search was conducted to identify studies meeting the inclusion criteria in the Pubmed (MEDLINE) and EMBASE databases in July 2025 for nearly a year. Our search strategy included both medical subject headings (MeSH) and free text terms relevant to the biologics.

Results: A total of 147 studies were screened and 37 clinical studies were ultimately selected in this review, drawing on peer-reviewed studies released within the previous calendar year. Adalimumab, infliximab, etanercept, golimumab, certolizumab pegol, secukinumab, bimekizumab, ixekizumab, tofacitinib, upadacitinib, and baricitinib had greater remittance in AS, with some side effects.

Conclusion: This comprehensive analysis assesses therapeutic outcomes and adverse effects of TNFi, IL17i, and JAKi in AS care.

Lipopolysaccharide (LPS) is a potent inducer of cytokine-mediated inflammatory responses. Although autophagy and LPS-induced inflammatory responses are related, it is unclear how autophagy regulates these inflammatory responses. We aimed to determine the effect of autophagy on the LPS-induced myeloid differentiation factor 88 (MyD88)/mitogen-activated protein kinase (MAPK)/nuclear transcription factor kB (NF-κB) signaling pathways in the inflammatory responses. We also determined the effect of autophagy on the MyD88-independent signaling pathway activated by LPS. To determine the effect of autophagy on LPS-induced inflammatory responses in RAW264.7 cells, we examined various in vitro assays by knockdown of autophagy-related protein 5 (ATG5), a key component of autophagy. ATG5 knockdown suppressed pro-inflammatory cytokines, including interleukin 6 and tumor necrosis factor α in LPS-stimulated RAW264.7 cells. Moreover, ATG5 knockdown also affected both MyD88-dependent (MAPK/ NF-κB) and MyD88-independent (interferon regulatory factor 3) signaling pathways. This study demonstrates that dysfunctional autophagy suppresses LPS-induced inflammatory responses through both MyD88-dependent and MyD88-independent pathways in RAW264.7 cells. We propose that targeting autophagy regulation is a promising therapeutic approach for many diseases in which inflammatory responses contribute to their onset and progression of the disease.

Objective: This study aimed to investigate whether esculentoside A (EsA) alleviates airway inflammation by modulating JAK2/STAT3-mediated mitochondrial apoptosis in an ovalbumin (OVA)-induced murine model of asthma.

Methods: Female BALB/c mice were sensitized and challenged with OVA to establish the asthma model. EsA (15 mg/kg) was administered intraperitoneally from day 17 for seven consecutive days. JAK2 inhibitor (Fedratinib, 60 mg/kg) and JAK2 agonist (C-A1, 100 μg/kg) were used to further validate the involvement of the JAK2/STAT3 pathway. Histological analysis, ELISA, Western blot, TUNEL, and mitochondrial function assays were performed to evaluate inflammatory response, apoptosis, and signaling pathways.

Results: EsA treatment significantly alleviated airway inflammation, as shown by reduced peribronchial inflammatory infiltration and lower inflammation scores, and decreased goblet cell hyperplasia and PAS staining scores. ELISA results showed that EsA significantly reduced IL-4, IL-13, and TNF-β levels in BALF and decreased serum OVA-specific IgE. Western blot revealed that EsA downregulated phosphorylated JAK2 and STAT3 levels, as well as proapoptotic markers (Bax, Cyt C, and cleaved Caspase-3), while upregulating the antiapoptotic protein Bcl-2. These effects were comparable to those of Fedratinib and were reversed by JAK2 agonist C-A1. Furthermore, EsA restored mitochondrial membrane potential (JC-1 ratio increased) and reduced mitochondrial ROS production, indicating improved mitochondrial function. TUNEL assays corroborated the antiapoptotic effect of EsA.

Conclusion: : EsA ameliorates OVA-induced airway inflammation in mice, likely by suppressing the JAK2/STAT3 signaling pathway and attenuating mitochondrial-dependent apoptosis. These findings suggest that EsA holds therapeutic potential as a novel anti-asthmatic agent targeting inflammatory and mitochondrial pathways.

Hymenoptera stings are a common occurrence worldwide, with a significant proportion of the general population experiencing at least one sting during their lifetime. The order Hymenoptera includes several species, such as honey bees, hornets, bumblebees, and yellow jackets, that cause hypersensitivity reactions. The most common form of hypersensitivity is systemic sting reaction mediated by specific immunoglobulin E (sIgE) to venom components. The prevalence of systemic sting reaction in the general population is estimated to be approximately 3%, while gross local reactions are reported in 2.4-26.4% of individuals, with higher proportions in beekeepers. Identification of the offender insect is crucial for proper diagnosis and treatment, but many patients are unable to correctly distinguish the responsible venom. Standard diagnostic tools, such as intradermal testing and Hymenoptera venom sIgE tests, play an important role in determining venom sensitivity. However, cross-reactivity between different venoms makes accurate identification difficult. In this study, we aim to analyze the clinical history of patients with Hymenoptera venom hypersensitivity and evaluate the diagnostic approach. Understanding these factors is important to improve diagnostic accuracy and optimize patient management. Further research is needed to improve diagnostic tools and develop personalized treatment strategies to reduce the risk of severe allergic reactions in susceptible individuals. Our study suggests that diagnostic tests should be performed rapidly in reactions that develop after an Apis sting, especially due to the significant decrease in Apis sIgE levels.