Hande Üçler Çınar

Purpose: Hyper-IgM syndromes (HIGM) are primary immunodeficiencies characterized by defective class-switch recombination (CSR) and impaired humoral immunity. While genetic causes such as CD40L and AICDA mutations are well established, a detailed comparison of B cell maturation dynamics across HIGM subtypes remains limited. To comprehensively characterize B cell immunophenotypes and functional responses in patients with HIGM and to delineate mutation-specific differences in B cell maturation and proliferation. Method: Four patients with genetically confirmed HIGM (one CD40L and three homozygous AICDA mutations, c.70C>T; p.R24W) and age- and sex-matched healthy controls were studied. Peripheral blood mononuclear cells were analyzed by multiparameter flow cytometry to define B cell subsets based on CD19, CD20, CD24, CD27, CD38, IgD, and IgM expression. B cell proliferation was assessed following CpG stimulation. Results: All patients exhibited a marked reduction of class-switched memory B cells (CD27⁺IgD⁻) and accumulation of naive B cells (CD27⁻IgD⁺), consistent with defective CSR. The CD40L -deficient patient demonstrated profound depletion of plasmablasts and precursor skewing, reflecting failure of germinal center formation. In contrast, AID patients showed preserved CD27 expression with variable expansion of transitional and plasmablast populations, suggesting intact T cell–dependent activation but intrinsic failure of CSR. Functional assays revealed heterogeneous proliferative responses in CD40L deficiency and AICDA -deficient patient, but impaired proliferation in another AICDA -deficient individual, highlighting inter-individual variability. Conclusion: Detailed immunophenotyping reveals distinct B cell maturation arrest points in CD40L - versus AICDA -associated HIGM. Flow cytometric analysis of B cell subsets provides valuable insights into disease mechanisms, supports differential diagnosis, and may inform clinical monitoring and therapeutic decision-making in HIGM.

Objective: This study aimed to systematically evaluate pediatric patients referred with suspected penicillin allergy and determine the rate of confirmed penicillin allergy.Materials and Methods: A retrospective study was conducted on 57 patients who presented to the Pediatric Allergy and Immunology Department of Istanbul Kanuni Sultan Süleyman Training and Research Hospital with suspected penicillin allergy between August 2023 and August 2025. All patients underwent specific IgE testing for amoxicillin, ampicillin, penicillin G, and penicillin V. Skin testing was performed in patients with parenteral drug reactions. Oral drug provocation testing was conducted in patients with negative specific IgE and skin tests.Results: The mean age was 7.4±4.9 years (median: 6 years). The most common suspected drug was amoxicillin-clavulanate (77.2%). Urticaria/angioedema (61.4%) was the most frequent reaction type. Specific IgE positivity was detected in only 3 patients (5.3%). Drug provocation testing was performed in 53 patients, with 51 patients (96.2%) tolerating the drug without complications and 2 patients (3.8%) showing positive reactions. Penicillin allergy was confirmed in 6 patients (10.5%), whereas it was excluded (delabeled) in 51 patients (89.5%).Conclusion: Our study demonstrated that 89.5% of penicillin allergy labels were incorrect. The low sensitivity of specific IgE testing was confirmed. Direct drug provocation testing is safe and effective in low-to-moderate-risk patients.

Background/Objectives: We aimed to evaluate the etiologic distribution of markedly elevated IgE (≥2000 IU/mL) and the association of parasitic infections with longitudinal IgE dynamics and National Institutes of Health Hyper-IgE Syndrome (NIH-HIES) score trajectories in pediatric patients. Methods: We retrospectively enrolled 127 pediatric patients with IgE ≥2000 IU/mL and ≥1 year of longitudinal follow-up at a tertiary allergy clinic (2019–2024). The primary outcome was the IgE reduction percentage difference between parasitic and non-parasitic groups. Results: Atopic sensitization was identified in 81.0% of tested patients; genetic evaluation was performed in 40 patients (31.5%), with confirmed IEI in one patient (0.8% of the cohort; 2.5% of those evaluated). Parasitic infections were present in 24.4% of patients (n = 31; intestinal parasites 15.7%, scabies 8.7%, hydatid cyst 1.6%; two patients had concurrent intestinal parasitosis and scabies). Median IgE reduction was 63.8% vs. 27.0% in parasitic versus non-parasitic groups (p < 0.001), persisting after multivariable adjustment (p < 0.001). Parasitic infection independently predicted IgE normalization below 2000 IU/mL (OR = 8.26; 95% CI: 2.76–24.68; p < 0.001). All three NIH-HIES inflammatory components (IgE, eosinophilia, eczema) regressed more often in the parasitic group (all p ≤ 0.01); no patient reached the ≥40-point HIES threshold. Conclusions: Parasitic infections produce a clinical phenotype overlapping with hyper-IgE syndrome, constituting a reversible phenocopy of primary immune dysregulation. In populations with substantial parasitic prevalence, parasitological evaluation may be a useful consideration in children with markedly elevated IgE and indeterminate clinical scores; however, this approach should complement rather than replace comprehensive clinical assessment.