Polina Kostova

Pediatric food allergy is an increasing public health challenge associated with severe allergic reactions, psychosocial burden, and healthcare inequalities. This study aimed to characterise molecular sensitisation patterns among Bulgarian children with suspected food allergy using component-resolved diagnostics and to evaluate family quality of life in a healthcare setting without access to epinephrine auto-injectors. A total of 1163 pediatric patients underwent molecular allergy testing using the ALEX² multiplex platform, while 90 caregivers completed structured quality-of-life questionnaires. A sensitisation threshold of >0.10 kUA/L was applied to maximise sensitivity for molecular profiling and co-sensitisation analyses. Tree nut allergens showed the highest sensitisation prevalence, predominantly involving Ana o 3, Pis v 1, Jug r 1, Cor a 9, and Cor a 14. Younger children showed a predominance of stable storage protein sensitisation, whereas older children more frequently demonstrated PR-10-associated cross-reactive profiles. Correlation analyses identified strong co-sensitisation clustering among phylogenetically related allergen families, particularly cashew-pistachio, walnut-hazelnut, mammalian milk, and fish allergens. Questionnaire responses revealed substantial psychosocial burden related to fear of anaphylaxis, chronic hypervigilance, restricted daily activities, and inadequate emergency preparedness. These findings highlight the importance of molecular risk stratification and underscore major unmet needs in pediatric food allergy management in Bulgaria.

Introduction: Airway remodelling in children with severe recurrent episodes of bronchial obstruction starts very early, from preschool age – a period in which the diagnosis of asthma is not yet confirmed. Assessing these early structural changes presents a challenge in clinical practice. Due to the limitations of invasive methods, reliable noninvasive markers of these changes are sought. Galectin-3 (Gal-3), a regulator of inflammatory and fibrotic processes, and Krebs von den Lungen-6 (KL-6), a marker of alveolar epithelial damage, are considered as indicators of lung remodelling. Methods: Forty-eight children were studied: 26 children under 4 years of age with recurrent episodes of wheezing (RW) and 22 with cystic fibrosis (CF). Children with RW were divided into two subgroups: those with a low frequency (≤3 episodes/year) and those with a high frequency (>6 episodes/year) of bronchoobstructive symptoms. CF patients were stratified according to genotype (ΔF508 homozygous or heterozygous), and all underwent computed tomography (HRCT). Serum Gal-3 and KL-6 levels were measured by the ELISA method. The correlation between Gal-3 and KL-6 and clinical severity in children with recurrent wheezing at preschool age, and between Gal-3 and KL-6 and radiologically confirmed structural lung changes in children with cystic fibrosis, was assessed. Results: Elevated Gal-3 levels were found in children with RW from infancy. Although the differences in median Gal-3 levels did not reach statistical significance in the two RW subgroups, children with a high frequency of wheezing were 1.76 times more likely to have elevated Gal-3 (>26 ng/mL) compared to those with a low frequency of RW (p = 0.02). In CF, Gal-3 levels were significantly higher in children with confirmed structural lung disease on HRCT compared to those without pathological changes (38.35 vs. 11.63 ng/mL, p = 0.001). The highest Gal-3 values were found in ΔF508 homozygous patients with bronchiectasis. KL-6 levels remained within the normal range for the pediatric population across all groups and did not correlate with the frequency of bronchoobstructive manifestations, genotype, or CT findings. Conclusion: Galectin-3 is a reliable biomarker for pediatric pulmonology practice, reflecting early pulmonary changes in children with frequent recurrent bronchoobstructive episodes and a risk of persistent manifestations, and it correlates with structural damage in cystic fibrosis patients. KL-6 has no diagnostic value in the early stages of pulmonary pathology.

Background: Recurrent infections in children may indicate underlying inborn errors of immunity. Early detection by combined immunologic and genetic testing is essential for accurate diagnosis and targeted intervention. Methods: This prospective study included 60 pediatric patients aged ≤18 years with recurrent infections, evaluated between 2022 and 2024. The median age at enrollment was 6.2 years ([IQR] 3.6–11.3). Immunological assessment included flow cytometric immunophenotyping of lymphocyte subsets, serum immunoglobulin profiling (IgG, IgA, IgM, IgE and IgG subclasses), complement (C3, C4), and vitamin D measurement. Microbiological cultures of sputum or pharyngeal swabs were collected. Whole Exome Sequencing (WES) was performed for genetic evaluation and results verified by Sanger sequencing. Results: A subset of patients had reduced CD4+ T cells, memory B cells or NK cells. Hypogammaglobulinemia, particularly of IgG2 and IgA subclasses, was common. Pathogenic bacteria, mainly Haemophilus influenzae and Staphylococcus aureus, were isolated in 45% of cases. WES identified pathogenic or likely pathogenic variants in TNFRSF13B, CFTR, IL10RA, MEFV and other genes. A possible association between MBL2 c.161 G>A and altered CD4+ T cell percentages, lower NK cell numbers and reduced CD8+ effector T cells could indicate immunomodulatory effects. Conclusion: Comprehensive immunogenetic profiling reveals distinct patterns of immune dysregulation and genetic susceptibility, supporting personalized diagnostic and therapeutic strategies, including immunoglobulin substitution, immunomodulation, and genetic counseling.

Food allergy is characterized by an abnormal immune reaction that occurs reproducibly upon exposure to a specific food. This immune response can lead to a variety of symptoms, the prevalence of food

Elevated immunoglobulin E (IgE) is a hallmark of allergic diseases. However, high IgE levels also occur in a number of other infectious and noninfectious diseases. In most cases, elevated IgE levels indicate allergy, eczema, or chronic skin infection. Very high IgE levels are not uncommon in patients with active eczema but more often indicate monogenic atopic disorder or inborn errors of immunity with an atopic phenotype. We conducted a retrospective study of 385 children with suspected immune deficiency referred to the clinic over a 9-year period. Measurement of IgE, IgG, IgA, IgM, and IgG subclasses in blood samples revealed that nearly one-third of the patients had elevated serum IgE levels. Most of the cases with elevated IgE were children with underlying atopy—mainly atopic dermatitis and, to a lesser extent, bronchial asthma—whereas 40.12% (37 children) had no atopy at all. In the most severe cases (with extremely elevated IgE or severe dermatitis), we confirmed genetic mutations for underlying immunodeficiency. Our results indicate that allergic phenotype should not be underestimated and that children with more severe allergic disease should be evaluated for an underlying inborn error of immunity. If inborn error of immunity (IEI) is suspected, a comprehensive immunologic evaluation is required. Genetic testing helps identify the specific genetic abnormality, which provides important insight into the immunopathogenesis of the disease and accurate determination of optimal therapy.

Background. It is presently known that several subsets of T-regulatory (Treg) cells, both natural and inducible maintain tolerance to environmental allergens. But the relative importance of distinct phenotypically defined Treg subsets for the clinical manifestations of IgE-mediated allergy has not been elucidated yet.The aim of the study was to investigate the phenotype and number of different Treg subpopulations from patients with IgE-mediated allergy compared with healthy non-allergic individuals.Materials and methods. A group of 20 patients with clinically manifested IgE allergy and a group of 10 healthy no allergic controls were included in the study. Peripheral blood samples were taken after informed consent. Percentage and absolute count (AC) of the following regulatory subsets: naive (CD45RO-FoxP3lo), memory (RO+FoxP3+), effector (Treg eff, RO+FoxP3hi), induced (CD39+CD134+), Thl7/Treg (CD196+FoxP3+CD4Treg); Tr1 (IL-10+FoxP3-), were determined using standard 8-parameter flow cytometry (BD FACSCanto II).Results and discussion. The share and AC of FoxP3+CD4 Treg was significantly decreased in sensitized patients as compared to controls (mean 0,6% vs. 3,3%, p0.05 and 8,7 vs. 55 cells/μl p0.001). In addition, a significantly decreased level of Tr1 cells was observed in the patients with allergy, 0,4% vs. 2,1 % in healthy controls (p0,05) as well for subset of Thl7/Treg (mean 7,7% vs. 28,4% in healthy persons, p0.01).Conclusion. The significantly decreased number of FoxP3+CD4 Treg as well as periphery induced Tr1 and Thl7/Treg cells in patients with respiratory allergy lead to dysregulation and loss of peripheral immune tolerance, which is the pathophysiological basis for development of widely spread allergic diseases like allergic rhinitis and bronchial asthma.