İntroduction: To evaluate the clinical, laboratory, and follow-up characteristics of pediatric patients diagnosed with food allergy (FA) in a tertiary pediatric immunology and allergy clinic. This retrospective study included 300 children diagnosed with FA between January 2018 and January 2022. Patients were classified into IgE-mediated, mixed-type, and non-IgE-mediated FA. Demographic features, clinical symptoms, diagnostic tests (skin prick test-SPT, specific IgE), nutritional patterns, and tolerance outcomes were analyzed. IgE-mediated FA was observed in 43.7%, mixed-type in 30.6%, and non-IgE-mediated in 25.7%. Cow's milk (67.3%) and egg white (50.6%) were the most frequent allergens. Anaphylaxis occurred in 6.3% of patients. Complementary feeding patterns varied across groups; dairy products were more common in the IgE-mediated group (40.6%), while vegetables were more frequently introduced in the non-IgE (65.7%) and mixed (37.5%) groups. Tolerance was most often achieved for cow's milk (80.1%), egg white (80.0%), and egg yolk (78.4%), with a median age of 3 years. In contrast, tolerance did not develop in 77% for walnut, 76.9% for hazelnut, and 71.4% for peanut. Primary immunodeficiency (PID) was identified in 21% of patients, predominantly transient hypogammaglobulinemia of infancy (79.0%). Multiple food allergies were significantly more frequent in patients with PID (42.8% vs. 35.8%, p=0.004). FA subtypes display distinct clinical and nutritional features. Routine immunologic evaluation may aid in the early identification of underlying PIDs in children with FA.

Inborn errors of immunity (IEI) are particularly prevalent in regions with high rates of consanguinity, yet the genetic profiles in these populations are underreported. This study aims to describe the clinical and molecular characteristics of IEI in a highly consanguineous population and investigate the impact of genetic diagnosis on patient management. This retrospective study included 52 patients with suspected IEI, as defined by the IUIS criteria. Clinical, immunological, and demographic data were recorded. Genetic analyses were performed primarily using next-generation sequencing (NGS) gene panels, and all pathogenic variants were confirmed by Sanger sequencing. Variants were interpreted in accordance with the ACMG guidelines. A total of 52 patients were included in the study, with 92% of the individuals born to consanguineous parents, comprising 28 females and 24 males. The mean age at diagnosis was 4.63 ± 2.5 years. The median duration of follow-up was three years. The overall incidence was 0.3% representing the proportion of patients diagnosed with IEI among those referred to our center during the study period. A high rate of consanguineous marriage was observed, reported in 92% of the cases. The most frequently represented category was Predominantly Antibody Deficiencies (PAD), accounting for 20 patients (38.5%), including 12 cases (23%) of transient hypogammaglobulinemia of infancy (THI) and 7 cases (13%) of selective IgA deficiency. Among the 52 patients, 3 (5.8%) were diagnosed with severe combined immunodeficiency (SCID): 1 patient had ADA deficiency, and two patients had DNA ligase IV deficiency (LIG4). Additionally, 14 patients (26%) were diagnosed with combined Immunodeficiencies (CID). Thirty patients were treated with IVIG, and 3 patients underwent HSCT. A molecular diagnosis was established in 33 patients (63%). Genetic findings influenced clinical management in 82% of variant-positive cases, including decisions regarding HSCT, targeted therapy, and genetic counseling. This study highlights the distinctive genetic characteristics of IEI in a population with high consanguinity, emphasizing the need to incorporate molecular diagnostics into standard immunology practice, particularly in areas where recessive disorders are prevalent.

Celiac disease (CD) and allergic diseases are immune-mediated disorders with overlapping clinical and immunologic features. The association between CD and selective immunoglobulin (Ig) A deficiency (sIgAD) is well-established, but limited data exist on the relationship between CD, other antibody deficiencies, and allergic diseases in children. This study aimed to evaluate the prevalence of allergic manifestations and immunologic abnormalities in children with CD. This prospective study included children with biopsy-confirmed CD, followed at a gastroenterology clinic from August 2022 to February 2023. Participants underwent comprehensive immunologic and allergic evaluation, including serum immunoglobulin levels, vaccine antibody responses, lymphocyte subgroup analysis, and allergy testing as clinically indicated. The cohort included 76 patients with a median age of 11 years and a median age at CD diagnosis of 5.8 years. Allergic manifestations included aeroallergen sensitivity (22.4%), allergic rhinitis (15.8%), allergic conjunctivitis (13.2%), food allergy (5.3%), and asthma and eczema (3.9% each). Immunologic evaluations revealed normal profiles in 69.7% of patients, while abnormalities included partial IgM deficiency (6.6%), unclassified hypogammaglobulinemia (5.3%), sIgAD (2.6%), and transient hypogammaglobulinemia of infancy (2.6%). Elevated IgE levels were observed in 13.2% of patients. This study highlighted a significant prevalence of allergic diseases and immunologic abnormalities in children with CD, extending beyond the commonly recognized association with sIgAD. These findings underscore the importance of comprehensive immunologic and allergic evaluation in children with CD.

Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic Primary Immunodeficiency (PID) in adults and children. Patients with CVID present with predominant antibody deficiency with varying degrees of impaired cellular immunity. CVID was previously a diagnosis of exclusion, which led to considerable uncertainty about which patients would qualify for subcutaneous or intravenous immunoglobulin (SCIG/IVIG) replacement. Over the last twelve years, several sets of diagnostic criteria have been published which identify these disorders with greater precision. These new CVID diagnostic criteria assist with decisions on treatment, particularly SCIG/IVIG replacement. With the advent of massively parallel genome sequencing technologies, it has become apparent that a significant proportion of individuals with a CVID phenotype have an underlying causative genetic defect. If such a pathogenic variant is identified, these individuals are removed from the overarching diagnosis of CVID and are deemed to have a CVID-like disorder caused by a specific Inborn Error of Immunity (IEI). New Zealand has had a long-standing customized PID genetic testing program. Two novel autosomal dominant pathogenic variants causing CVID-like disorders, consequent to haploinsufficiency of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NFKB1) and Transcription Factor 3 (TCF3), were identified in New Zealand families. The latter pathogenic variant was shown to have an epistatic interaction with TNFRSF13B (TACI) in a patient with a digenic CVID-like disorder. Epistasis is the synergistic, non-linear interaction between two or more genetic loci, leading to much more severe (or much milder) disease. This perspective reviews the current understanding of these disorders with contributions from three New Zealand-based studies: The Prospective NZ CVID and the NZ hypogammaglobulinemia sub-studies as well as a large retrospective case series of Transient Hypogammaglobulinemia of Infancy (THI). These clinical and genomic studies have offered insights into the complexities of these rare PIDs. This review examines current areas of uncertainty in the diagnosis of of these disorders.

Introduction: Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder characterized by reduced serum immunoglobulin G (IgG) levels in early infancy. Objective: This study aimed to identify potential risk factors associated with THI. Methods: Children with THI and normoglobulinemic healthy children were compared by using a questionnaire that addressed possible risk factors. Results: In total, 108 participants were enrolled, 54 patients with THI and 54 healthy controls. The median age at diagnosis of the patients with THI was 17 months (range, 4-38 months), and 40 (74.1%) were boys. In the control group, the median age was 22 months (range, 16-61 months), and 27 (50.0%) were boys. Male sex (p = 0.004), cesarean section birth (p = 0.003), low maternal education (p = 0.001), low paternal education (p = 0.004), analgesic use during pregnancy (p = 0.001), antibiotic use during pregnancy (p = 0.001), multivitamin use during pregnancy (p = 0.001), gestational diabetes or preeclampsia (p = 0.039), smoking exposure (p = 0.001), atopic disease (p = 0.001), and familial atopy (p = 0.001) were associated with THI, whereas low socioeconomic level (p = 0.001) and breast-feeding for > 6 months (p = 0.032) were less likely in the THI group. Conclusion: There are several features of pregnancy history and family demographics that are associated with THI.