Research

Int Arch Allergy Immunol. 2026 Feb 19:1-16. doi: 10.1159/000551104. Online ahead of print.

ABSTRACT

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.

METHODS: 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.

RESULTS: 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).

CONCLUSION: FA subtypes display distinct clinical and nutritional features. Routine immunologic evaluation may aid in the early identification of underlying PIDs in children with FA.

PMID:41712476 | DOI:10.1159/000551104

Int J Dermatol. 2026 Feb 18. doi: 10.1111/ijd.70341. Online ahead of print.

NO ABSTRACT

PMID:41709310 | DOI:10.1111/ijd.70341

Pediatr Int. 2026 Jan-Dec;68(1):e70326. doi: 10.1111/ped.70326.

ABSTRACT

BACKGROUND: Clinical manifestations of Chédiak-Higashi syndrome (CHS), an autosomal recessive disorder caused by LYST gene variants, include immunodeficiency and neurologic deficits. This study investigated the effects of defective LYST on neurodegenerative features by the morphological analysis of organelles in dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) derived from CHS patients.

METHODS: iPSCs derived from CHS patients were analyzed by immunostaining with antibodies against microtubule-associated protein 2 and tyrosine hydroxylase, periodic acid-Schiff (PAS) staining, electron microscopy, and staining with a fluorescent probe to monitor autophagy.

RESULTS: iPSC-derived neurons contained PAS-positive giant granules and lipofuscin-like granules. Electron microscopy revealed enlarged lysosomes with electron-dense granules and filament-like structures. The number and brightness of autophagosomes and autolysosomes were markedly increased in CHS iPSC-derived neurons under basal culture conditions. CHS iPSC-derived neuronal mitochondria were enlarged, polymorphic, and hypertrophic.

CONCLUSIONS: CHS iPSC-derived neurons contained abnormal organelles, including lysosomes, autophagosomes, and mitochondria, which may be related to the neurodegenerative features of CHS.

PMID:41703749 | DOI:10.1111/ped.70326

Front Immunol. 2026 Feb 2;17:1758410. doi: 10.3389/fimmu.2026.1758410. eCollection 2026.

ABSTRACT

INTRODUCTION: 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.

METHOD: 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.

RESULTS: 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.

CONCLUSION: 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.

PMID:41705238 | PMC:PMC12907321 | DOI:10.3389/fimmu.2026.1758410

Expert Rev Clin Immunol. 2026 Feb 16. doi: 10.1080/1744666X.2026.2633137. Online ahead of print.

ABSTRACT

INTRODUCTION: Inborn errors of immunity (IEIs), also known as primary immunodeficiency diseases (PIDs) since 2017 Inborn Errors of Immunity Committee classification, comprise a heterogeneous group of genetic disorders resulting in impaired immune development and function. Malignancy is a major challenge in IEIs, particularly in those with defects in DNA repair, tumor suppression, immune surveillance, or chronic inflammatory control, highlighting the close interplay between immune dysfunction and oncogenesis.

AREAS COVERED: Hematologic malignancies, especially non-Hodgkin lymphomas, predominate in IEIs, though epithelial tumors also occur and present at younger ages with poorer outcomes. Both intrinsic factors – such as genomic instability and defective lymphocyte maturation – and extrinsic factors, including chronic inflammation, oncogenic viral infections, and iatrogenic exposures, contribute to cancer development. Subtypes such as ataxia-telangiectasia, Nijmegen breakage syndrome, Wiskott – Aldrich syndrome, and common variable immunodeficiency show particularly high malignancy rates. Defects in specific immune pathways, including CD40L or IL-10 receptor signaling, may predispose to organ-specific or virus-driven cancers.

EXPERT OPINION: Although hematopoietic stem cell transplantation remains curative for select IEIs, post-transplant malignancy risk persists. A deeper understanding of shared molecular pathways linking immunodeficiency and cancer is essential to refine early diagnosis, risk stratification, and targeted management in this vulnerable population.

PMID:41693687 | DOI:10.1080/1744666X.2026.2633137

Rare Dis Orphan Drug J. 2025 Oct 14;4(4):rdodj.2025.42. doi: 10.20517/rdodj.2025.42.

ABSTRACT

Inborn errors of immunity (IEIs), also known as primary immunodeficiencies, are a group of rare inherited disorders that affect the immune system. They result in severe, opportunistic infections, severe autoimmune manifestations and a predisposition to malignancy. The only curative treatment for many years has been allogenic haematopoietic stem cell transplantation (alloHSCT). However, this requires the availability of a suitable donor and has risks of morbidity and mortality. Autologous gene therapy (GT) abrogates the immunological complications of alloHSCT and uses the patient’s own cells, removing the need for a donor. Preclinical proof-of-concept and clinical trials in humans have demonstrated that GT is safe and effective and can be used to correct a variety of IEIs. In this review, we outline the progress in developing GT for IEIs over the last four decades. We describe the gene editing technologies available to correct IEIs and their current applications. We also examine advances in GT development, the challenges to its application, and discuss future developments in the field, including emerging in vivo approaches.

PMID:41693912 | PMC:PMC7618722 | DOI:10.20517/rdodj.2025.42

JPGN Rep. 2025 Oct 23;7(1):11-13. doi: 10.1002/jpr3.70099. eCollection 2026 Feb.

ABSTRACT

Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare autosomal recessive primary immunodeficiency. Patients with DOCK8 deficiency typically present at early age with allergic manifestations, cutaneous and respiratory infections, raised immunoglobulin E, and they have an increased risk of developing malignancies. Hematopoetic stem cell transplantation (HSCT) is the only curative treatment for DOCK8 deficiency. We present a female paediatric patient with DOCK8 deficiency who was assessed for HSCT, but underwent liver transplantation fist in view of decompensated liver disease. The patient, unfortunately, succumbed secondary to infectious complications in the post-op period.

PMID:41695074 | PMC:PMC12894047 | DOI:10.1002/jpr3.70099

Shock. 2025 Dec 11. doi: 10.1097/SHK.0000000000002768. Online ahead of print.

ABSTRACT

BACKGROUND: Sepsis is a persistent systemic inflammatory disease involving multiple organ failure caused by a dysregulated immune response to infection. As primary effector cells in innate immunity, neutrophils significantly contribute to combating infections and mediating inflammatory responses. The aim of this study was to evaluate the prognostic significance of neutrophil-related genes (NRGs) in sepsis and their relationship with the immune microenvironment.

METHODS: This study was drawing on transcriptomic data and clinical characterization of sepsis patients from the GEO database. Sepsis prognostic genes were discovered through a combination of differential analysis, weighted gene co-expression network analysis (WGCNA), and univariate cox regression analysis. Molecular subtypes of sepsis were identified by consensus clustering methods, survival differences between subtypes were compared and gene enrichment analysis was performed. Further univariate cox regression analysis and LASSO combined were performed to identify sepsis feature genes. Utilizing multivariate cox regression analysis, a prognostic model was developed, and its predictive capability was subsequently examined through receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analyses. Subsequently, immune cell infiltration and gene enrichment were assessed in the various risk groups.

RESULTS: This study identified the presence of two molecular subtypes in sepsis, with Cluster1 patients having significantly better survival than Cluster2. The prognostic model based on NRGs (RCBTB2, KRT23, KLF9, GIMAP4 and CD84) in this study significantly differentiated the survival prognosis of high risk and low risk patients. The low risk patient group showed significant enrichment in immune related pathways (T cell receptor signaling and primary immunodeficiency), while the high risk group primarily exhibited significant enrichment in metabolism related pathways (glycine serine and threonine metabolism).

CONCLUSION: Risk models constructed on the basis of NRGs are effective in predicting survival outcomes and immune profiles of sepsis patients, providing a new perspective on the link between NRGs and sepsis.

PMID:41697141 | DOI:10.1097/SHK.0000000000002768

J Clin Immunol. 2026 Feb 14. doi: 10.1007/s10875-026-01993-4. Online ahead of print.

NO ABSTRACT

PMID:41688586 | DOI:10.1007/s10875-026-01993-4

Transpl Infect Dis. 2026 Feb 13:e70155. doi: 10.1111/tid.70155. Online ahead of print.

ABSTRACT

BACKGROUND: Infection is a common complication following umbilical cord blood transplantation (UCBT), yet comprehensive data on pediatric patients with inborn errors of immunity (IEIs) in China are scarce. This study aimed to characterize infection profiles and their prognostic implications in this population.

METHODS: We retrospectively analyzed 165 IEIs patients undergoing UCBT between January 2015 and June 2020. The post-transplantation period was divided into early (≤ 30 days) and middle (31-100 days) stages.

RESULTS: Within 100 days, 115 patients (69.7%) experienced 217 infection episodes. Engraftment failure was an independent predictor of infection risk within 100 days (OR = 2.97, p = 0.04). Low pre-transplantation IgM levels and graft-versus-host disease (GVHD) prophylaxis with calcineurin inhibitors (CNIs) plus mycophenolate mofetil (MMF) increased early-stage infection risks (p < 0.05). Infections at the middle stage were correlated with Grade II-IV acute GVHD (p = 0.03). Bloodstream infections (BSIs) were linked to CNIs combined with MMF and lower total nucleated cell counts in cord blood (p < 0.05). Early-stage infected group exhibited significantly poorer survival versus uninfected and middle-stage groups (p < 0.001). Patients without bacterial infections had higher survival rates than those with carbapenem-resistant or non-resistant infections (p < 0.05). BSIs were associated with poor prognosis (p < 0.05), while cytomegalovirus infection showed no significant survival impact (p = 0.05).

CONCLUSIONS: Infections are highly prevalent in IEIs children post-UCBT, with early-stage events and BSI portending poorer outcomes. These findings advocate for risk-stratified surveillance and preemptive strategies in high-risk subgroups.

PMID:41688817 | DOI:10.1111/tid.70155