Research

Iran J Allergy Asthma Immunol. 2025 Oct 29;24(6):860-866. doi: 10.18502/ijaai.v24i6.20163.

ABSTRACT

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessive disease with varying degrees of clinical phenotypes and disease severity. The phenotypic spectrum of the disorder has expanded from vasculitis with stroke to include pure red cell aplasia, bone marrow failure, autoimmune cytopenia, lymphoproliferation, and variable degrees of immunodeficiency. Here, we describe two cases of ADA2 deficiency: one presented with an early-onset stroke that resembled an early-onset polyarteritis nodosa (PAN), and the other as an adult-onset vasculitis that progressed to severe neutropenia with recurrent infection and lymphoproliferation. Patient 1, a 10-year-old male, had a reported pathogenic ADA2 homozygote variant; c.139G˃C (p.Gly47Arg), and patient 2, a 34-year-old male, had a reported likely pathogenic homozygous ADA2 variant; c.578C>T (p.Pro193Lys). Our second patient was the first DADA2 patient who showed that DADA2 is not a static disease and can progress from vasculitis to bone marrow failure in the course of the disease. Therefore, the previous recommendation introducing anti-TNF-α as a preferred treatment for vasculitis manifestations and hematopoietic stem cell transplantation as the preferred treatment for bone marrow failure can no longer apply. We should consider HSCT for DADA2 patients from the very beginning. The Physician has to be aware of this monogenic disorder’s varied presentation and multi-organ involvement. Early recognition and proper treatment are crucial for this potentially fatal disease.

PMID:41266270 | DOI:10.18502/ijaai.v24i6.20163

Pediatr Dermatol. 2025 Nov 20. doi: 10.1111/pde.70082. Online ahead of print.

ABSTRACT

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive primary immunodeficiency characterized by partial oculocutaneous albinism, neurologic involvement, and a predisposition to severe infections. Patients are particularly susceptible to developing hemophagocytic lymphohistiocytosis (HLH), which significantly worsens prognosis. We report the case of a 19-year-old male with CHS, under long-term immunosuppressive therapy for chronic HLH, who developed chronic VZV infection. Despite treatment with valacyclovir, the lesions progressed, and virological investigations confirmed the diagnosis of acyclovir-resistant varicella-zoster virus (VZV). The clinical course was marked by the appearance of neurological symptoms and a fatal outcome. To our knowledge, this is the first reported fatal case of chronic VZV infection with systemic dissemination in a patient with CHS. This case highlights the risk of resistance associated with long-term prophylaxis and the complexity of managing herpesvirus infections in immunocompromised patients receiving JAK inhibitors.

PMID:41262052 | DOI:10.1111/pde.70082

Front Pediatr. 2025 Nov 4;13:1663784. doi: 10.3389/fped.2025.1663784. eCollection 2025.

ABSTRACT

BACKGROUND: Cavernous sinus tuberculosis is an extremely rare manifestation of central nervous system tuberculosis in children, with only two cases reported worldwide. It can mimic malignancy or other inflammatory conditions. Its occurrence in children with primary immunodeficiency, particularly major histocompatibility complex (MHC) class II deficiency, has not yet been described.

CASE REPORT: We report an 11-year-old girl with a history of recurrent infections and chronic otitis media. She presented with right orbital swelling, severe headaches, and exophthalmos. Imaging revealed an extensive mass in the sinonasal and orbital regions, extending to the skull base and cavernous sinus. A computed tomography-guided biopsy and histopathology, supported by PCR testing for Mycobacterium tuberculosis, confirmed extensive orbital and cervicofacial tuberculosis. An immunological evaluation and genetic analysis revealed familial MHC class II deficiency. The patient received anti-tuberculosis therapy [isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) followed by isoniazid and rifampin (HR)], leading to clinical and radiological improvement. She continues with intravenous immunoglobulin replacement therapy every 21 days while awaiting a bone marrow transplantation.

CONCLUSIONS: This case highlights the importance of considering tuberculosis in atypical cavernous sinus lesions in children, especially in endemic regions. Severe or unusual infections should prompt evaluation for underlying immunodeficiency.

PMID:41262919 | PMC:PMC12623361 | DOI:10.3389/fped.2025.1663784

Pediatr Blood Cancer. 2025 Nov 18:e70006. doi: 10.1002/pbc.70006. Online ahead of print.

ABSTRACT

Revaccination in pediatric post-hematopoietic stem cell transplant (HSCT) patients is important for preventing vaccine-preventable infections. Published guidelines recommend revaccination based on time elapsed post-transplant, though the optimal timing remains unclear. Since May 2019, our institution adopted an accelerated revaccination schedule commencing 6 months post-HSCT and we report our experience. Our study supports the accelerated revaccination schedule, as most pediatric patients were able to mount sufficient immune responses using hepatitis B seroconversion as a surrogate. With the accelerated revaccination schedule, this could also potentially shorten the vulnerable period where patients are at risk of severe vaccine-preventable infections.

PMID:41254854 | DOI:10.1002/pbc.70006

ACG Case Rep J. 2025 Nov 17;12(11):e01891. doi: 10.14309/crj.0000000000001891. eCollection 2025 Nov.

ABSTRACT

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder causing hypogammaglobulinemia. Although rare, nodular regenerative hyperplasia is the most common liver complication in CVID, which can progress to noncirrhotic portal hypertension. We report a case of a young male with CVID presenting with recurrent parastomal bleeding secondary to noncirrhotic portal hypertension from CVID-associated nodular regenerative hyperplasia.

PMID:41256184 | PMC:PMC12622657 | DOI:10.14309/crj.0000000000001891

Turk Arch Pediatr. 2025 Oct 14;60(6):632-639. doi: 10.5152/TurkArchPediatr.2025.25204.

ABSTRACT

OBJECTIVE: Sepsis remains a major cause of morbidity and mortality in pediatric intensive care units (PICUs). Community-acquired sepsis presents distinct challenges in children due to immature immunity, variable clinical features, and emerging antimicrobial resistance. This study aimed to evaluate the clinical characteristics, microbiological profile, treatment, and mortalityrelated possible risk factors for mortality in pediatric community-acquired sepsis.

MATERIALS AND METHODS: This retrospective single-center study included 107 previously healthy children diagnosed with community-acquired sepsis and admitted to the PICU between February 2020 and June 2023. Demographic, clinical, laboratory, and microbiological data were retrieved from electronic medical records. Patients were analyzed based on culture positivity and survival status.

RESULTS: Among 1853 PICU admissions, 107 met the inclusion criteria. The median age was 2.5 years, and the overall mortality rate was 6.5%. Blood culture positivity was 14%, with Staphylococcus aureus as the most common pathogen (46.7%), followed by Pseudomonas and Acinetobacter species (13.3% each). Pulmonary involvement was the most common infection site (28%). Mortality was significantly associated with acute kidney injury (AKI), invasive mechanical ventilation, and longer ventilation duration. Culture positivity correlated with longer hospital and noninvasive ventilation duration.

CONCLUSION: Staphylococcus aureus was the leading cause of pediatric community-acquired sepsis. Critical complications such as AKI, mechanical ventilation, and a higher number of red blood cell transfusions were linked to mortality. All children with proven gram-negative sepsis were under 1.5 years, and 2 were later diagnosed with primary immunodeficiency, suggesting that early gram-negative infections in infants may reflect an underlying immune defect, as immunodeficiencies predispose to sepsis caused by unusual or atypical pathogens. Timely diagnosis and careful management are vital for better outcomes in vulnerable patients.

PMID:41257475 | DOI:10.5152/TurkArchPediatr.2025.25204

Front Immunol. 2025 Oct 30;16:1570328. doi: 10.3389/fimmu.2025.1570328. eCollection 2025.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI) are a heterogeneous group of different disorders characterized by a defect in the function and/or components of the immune system. Malignancy is the second common cause of death following recurrent infections.

AIM: We present our experience in Children Cancer Hospital Egypt (CCHE-57357) in diagnosing IEI patients who first presented with malignancy rather than infections.

METHODS: Data of 19 IEI patients with malignancy referred to the immunology clinic was collected. The reasons for referral were stunted growth or presence of bronchiectasis at presentation, persistent eczema, significant chemotoxicity, history of recurrent infection either during or after stoppage of chemotherapy, and relapse of lymphoid malignancy after auto-BMT.

RESULTS: The patients comprised 14/5 men/women. Their median age at diagnosis with malignancy was 7 years (1.5-16 years). In addition, 13/19 had lymphoma (Hodgkin’s/non-Hodgkin’s) and 6/19 patients had leukemia. Moreover, 9/19 had history of repeated infections, 4/19 had failure to thrive, 5/19 had clubbing, 4/19 had bronchiectasis, 3/19 had significant chemotoxicity, 8/19 had low immunoglobulin, 12/19 had abnormal lymphocyte subsets, and 3/19 had a relapse of the original disease. Genetic testing was done to 18/19. The diagnoses based on genetic and/or immunological investigation according to the IUIS classification were 7/19 (37%) immune-dysregulation, 4/19 (21%) combined immunodeficiency with syndromic features, 3/19 (15.7%), combined immunodeficiency, 3/19 (15.7%) predominantly antibody defect, and 2/19 (10.5%) bone marrow failure defect.

CONCLUSION: Collaborative work between immunologist and oncologist helped in diagnosing patients with IEI who first presented with malignancy.

PMID:41246311 | PMC:PMC12611879 | DOI:10.3389/fimmu.2025.1570328

Front Immunol. 2025 Oct 30;16:1662899. doi: 10.3389/fimmu.2025.1662899. eCollection 2025.

ABSTRACT

Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional corepressor involved in immune regulation via IRF1-mediated interferon signaling inhibition. Pathogenic IRF2BP2 variants are associated with common variable immunodeficiency, primarily affecting B-cell maturation. We report a 47-year-old female with immunodeficiency and systemic inflammation, including primary biliary cholangitis and unclassified arthritis, who was detected to carry a novel heterozygous de novo missense variant in the IRF2BP2 gene (c.1663T>A; p. Cys555Ser). Immunophenotyping revealed naïve B-cell predominance, with a loss of memory B cells and impaired plasmablast differentiation, indicating late-stage disturbed B-cell differentiation/maturation. CD4⁺ T cells demonstrated Th1 polarization with reduced Th2 subsets, whereas Th17 and Treg populations exhibited no obvious changes. Considering that IRF2BP2 negatively regulates STAT1-driven transcription via IRF1 suppression, the observed Th1 polarization suggests improved STAT1 activity. This case underscores the combined humoral and cellular immune dysregulation due to IRF2BP2 dysfunction, expanding the clinical spectrum to encompass inflammatory phenotype.

PMID:41246352 | PMC:PMC12611837 | DOI:10.3389/fimmu.2025.1662899

ASM Case Rep. 2025 Aug 5;1(6):e00060-25. doi: 10.1128/asmcr.00060-25. eCollection 2025 Nov.

ABSTRACT

BACKGROUND: Medicopsis romeroi only rarely causes infection in immunocompromised individuals. We report a rare case of invasive infection in a specific primary immunodeficiency not arising from primary cutaneous infection.

CASE SUMMARY: A 16-year-old male with chronic granulomatous disease (CGD) developed progressively enlarging diffuse pulmonary nodules in the setting of admission with obstructive hydrocephalus. A transthoracic biopsy grew a dematiaceous mold, identified as Medicopsis romeroi through DNA sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA (rDNA). The nodules progressed despite a combination of posaconazole, isavuconazole, terbinafine, and liposomal amphotericin B. A course of HLA-compatible granulocytes was initiated, resulting in stabilization of the infection.

CONCLUSION: This is a rare case of M. romeroi causing an invasive fungal infection of a visceral organ, the second documented M. romeroi infection in a CGD patient, and a report of a novel treatment regimen for this pathogen.

PMID:41244279 | PMC:PMC12584179 | DOI:10.1128/asmcr.00060-25

J Allergy Clin Immunol. 2025 Nov 14:S0091-6749(25)01126-1. doi: 10.1016/j.jaci.2025.10.033. Online ahead of print.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI), or primary immune disorders (PID), predispose individuals to infections, autoimmunity, inflammation, allergy, and malignancy. Malignancies are a major cause of morbidity and mortality in IEI/PID patients, with poorer outcomes compared to the general population.

OBJECTIVES: This European Society for Immunodeficiencies Registry (ESID-R) study aimed to determine the frequency and types of malignancies in IEI/PID patients and to assess clinical management approaches across Europe.

METHODS: Descriptive analyses were performed on malignancy data within each IEI category. Additionally, an ESID-R survey (05/2022-03/2024) collected data on management strategies and challenges.

RESULTS: Of 19,959 IEI/PID patients, 1,783 (8.9%) developed malignancies, of whom 27.1% presented malignancy as first manifestation of IEI/PID. A total of 1,210 malignancies were specified; B-cell non-Hodgkin lymphoma was most common (24.2%). Detailed malignancy-IEI/PID association maps are provided. Predominantly antibody deficiencies accounted for 59.1% of malignancy cases, with a higher median age at first malignancy (43.6 years) compared to other IEI/PID categories, e.g., combined immunodeficiencies with syndromic or associated features (11.7 years). Survey findings revealed oncological treatment was modified due to IEI/PID in 21.5% of cases, with assumed negative impacts of IEI/PID on complications and outcomes (in 27.4% and 30.7%, respectively). IEI/PID influenced transplant decisions in 16.5% of cases. Management practices like interdisciplinary decision finding and guideline availability were recorded.

CONCLUSION: This study provides comprehensive epidemiological data on malignancies in IEI/PID, highlighting the need for tailored screening and management. Survey results emphasize the real-world challenges and support the development of IEI/PID-specific oncologic surveillance guidelines and treatment strategies.

PMID:41242640 | DOI:10.1016/j.jaci.2025.10.033