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Ann Allergy Asthma Immunol. 2025 Oct 5:S1081-1206(25)01224-4. doi: 10.1016/j.anai.2025.09.026. Online ahead of print.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI) have been increasingly well characterized on the molecular and genetic levels. Their clinical recognition and management among practicing allergist-immunologists remain challenging.

OBJECTIVE: To evaluate the consultative practices of allergist-immunologists in diagnosing and managing IEIs by identifying subtypes encountered, current approaches, multidisciplinary collaboration, barriers, and educational needs.

METHODS: The American College of Allergy, Asthma, and Immunology distributed a 30-question web-based survey assessing IEI experience via SurveyMonkey to U.S.-based members over a four-week period during the spring of 2024.

RESULTS: Most IEI consultations originated from outpatient primary care settings (82%), with 56% of respondents providing both outpatient and inpatient consultations. Frequently encountered IEIs included common variable immunodeficiency (CVID) (100%), specific antibody deficiency (99%), selective IgA deficiency (97%), and C1 esterase inhibitor deficiency (90%). Less frequently encountered were Chediak-Higashi syndrome (40.5%) and type I interferonopathies (41%). The greatest need for subspecialty input was from hematology/oncology for quantitative phagocyte cell defects (89%) and ALPS-FAS (74%). Severe combined immunodeficiency (SCID) and defects of cytotoxicity (50%) most often required expert immunology consultation. The top educational priorities were genetic testing (61%) and gene therapy (60%). The major barriers were complexity and wide range of IEIs (39%) and low referral volume (36%). Comfort levels and need for knowledge varied significantly by practice type and clinician age. A major limitation of this study was the over representation of academic practitioners.

CONCLUSION: This ACAAI study provides insight into the current consultative practices and management of allergist-immunologists engaging in IEI care. These findings highlight the critical need for enhanced training, improved access to multidisciplinary support, and targeted continuing education to optimize care for patients with these complex disorders.

PMID:41057108 | DOI:10.1016/j.anai.2025.09.026

J Pediatr Nurs. 2025 Oct 6;85:623-630. doi: 10.1016/j.pedn.2025.09.025. Online ahead of print.

ABSTRACT

PURPOSE: This study investigated the effects of watching Epic Roller Coasters with virtual reality (VR) or a tablet on pain, fear, and emotional behaviors related to peripheral venous catheterization in children before intravenous immunoglobulin (IVIG) administration.

DESIGN AND METHODS: A crossover randomized controlled study was conducted with children aged 4-12 years who had primary immunodeficiency disorder (PID). Participants were randomized into two groups: VR/tablet group (n = 15) and Tablet/VR group (n = 16). Pain was measured during the procedure. Fear and emotional appearance were measured at 3 time points (before catheter insertion, during catheter insertion/during interventions, post-intervention).

RESULTS: In the VR/Tablet group, 46.7 % (n = 7) and in the Tablet/VR group, 50 % (n = 8) of the children were female. In both groups, the mean pain was lower in those who underwent VR and higher in those who used tablets (F = 26.44, p < 0.001). While the fear (F = 14.58, p < 0.001) and emotional appearance (F = 8.312, p < 0.001) scale scores increased when switching from VR to tablet, the fear scores decreased when switching from tablet to VR. While the fear and emotional appearance scale scores were lower in the VR group, the scores were higher in the tablet group (p < 0.05).

CONCLUSIONS: VR application was more effective than tablets in reducing pain, fear, and negative emotional behaviors related to IV catheterisation in children with PID.

PRACTICE IMPLICATIONS: VR was more effective than tablet use in reducing pain, fear, and negative emotions during IV access in children with PID. It is a practical non-pharmacological application in the nursing care of children with PID.

PMID:41056743 | DOI:10.1016/j.pedn.2025.09.025

Medicine (Baltimore). 2025 Oct 3;104(40):e44935. doi: 10.1097/MD.0000000000044935.

ABSTRACT

This study actively monitors patients with primary immunodeficiency under the age of 18 to understand the risk of adverse reactions after vaccination and provide references for developing vaccination evaluation measures for children with special health conditions. A questionnaire survey was conducted on patients diagnosed with primary immunodeficiency, collecting diagnosis and treatment information as well as the vaccination records of live vaccines. Two stool samples were collected for virus detection and the vaccine-derived poliovirus was analyzed. A total of 26 primary immunodeficiency patients were enrolled among 3312 monitored cases, including 5 cases of severe combined immunodeficiency, 7 cases of primary antibody deficiency, and 14 cases of other types of immunodeficiency. Among the 21 cases with clear vaccination records, the vaccination rate of BCG and oral poliovirus vaccine were 95.24% and 71.43%, respectively. Among them, the vaccination rates of both vaccines for patients with severe combined immunodeficiency were 100% and 60.00%, respectively; and for patients with primary antibody deficiency were 100%. It was found that 1 patient with severe combined immunodeficiency had disseminated BCG infection after vaccination, and type Ⅲ immunodeficiency-associated vaccine-derived poliovirus was detected in his stool samples. The proportion of primary immunodeficiency patients receiving live vaccines is high, and there is a risk of adverse reactions after vaccination. It is recommended to improve the awareness and ability of recognizing vaccination for children with immunodeficiency, promote the active monitoring of children with immunodeficiency in hospitals, and adjust the immunization strategy for polio vaccine in a timely manner.

PMID:41054950 | DOI:10.1097/MD.0000000000044935

Blood Adv. 2025 Oct 6:bloodadvances.2025018106. doi: 10.1182/bloodadvances.2025018106. Online ahead of print.

NO ABSTRACT

PMID:41052414 | DOI:10.1182/bloodadvances.2025018106

Front Immunol. 2025 Sep 19;16:1646135. doi: 10.3389/fimmu.2025.1646135. eCollection 2025.

ABSTRACT

T-cell activation is a highly regulated process requiring both antigen recognition via the T-cell receptor (TCR) and co-stimulatory signaling, notably through the co-stimulatory receptor CD28. Here, we introduce an optogenetic platform for reversible and tunable full activation of human T cells that does not require genetic modification. We engineered opto-CD28-REACT, a recombinant protein comprising an anti-CD28 single-chain variable fragment, GFP, and phytochrome-interacting factor 6 (PIF6). This construct binds CD28 and thereby attaches PIF6 to CD28. Upon red light (630 nm) illumination, PIF6 binds to PhyB tetramer-coated beads, triggering CD28 signaling that can be attenuated by far-red light (780 nm) in 2 min. We show that opto-CD28-REACT synergizes with opto-CD3ϵ-REACT-a complementary optogenetic tool targeting the TCR complex-to induce light-dependent activation of both Jurkat cells and primary human T cells. Co-stimulation through both opto-REACT systems promotes ERK phosphorylation, upregulation of the activation markers CD69 and CD25, interleukin-2 (IL-2) secretion, and T-cell proliferation, reaching levels similar to conventional antibody-mediated stimulation. This strategy enables precise optical control over TCR and CD28 signaling in non-genetically modified T cells, offering a powerful approach for dissecting the regulatory dynamics of T-cell activation and advancing applications in synthetic immunology.

PMID:41050677 | PMC:PMC12491302 | DOI:10.3389/fimmu.2025.1646135

Front Med (Lausanne). 2025 Sep 19;12:1624815. doi: 10.3389/fmed.2025.1624815. eCollection 2025.

ABSTRACT

BACKGROUND: Existing studies substantiate the notion that CGB5 plays a pivotal role in various cancers, including gastric and ovarian cancers, and is strongly associated with patient prognosis. However, to date, there have been no comprehensive reports investigating the role of CGB5 in pan-cancer analysis.

METHODS: In this study, an in-depth investigation of CGB5 in pan-cancer was conducted through multiple public databases, including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), UALCAN, cBioPortal Platform, Gene Set Cancer Analysis (GSCA), Kaplan-Meier Plotter, TIMER, TISIDB, SangerBox Website, and Metascape database. The genomic, transcriptomic, epigenetic, immune microenvironmental, and clinical prognostic significance of CGB5 across various cancers was systematically analyzed. Furthermore, CGB5 expression in gastric cancer cells was experimentally detected, and the potential mechanisms underlying its impact on prognosis were elucidated.

RESULTS: This study shows that CGB5 exhibits diverse expression patterns in most tumors, including high, low, or no significant expression changes. Compared to normal tissues, CGB5 is significantly up-regulated in six tumor types, such as liver, lung, and gastric cancers. Its expression correlates positively with tumor stroma content and immune grading but negatively with immunological markers. Additionally, CGB5 is associated with specific immune sub-types in various cancers, including endometrial, testicular germ cell, and gastric adenocarcinoma, and closely linked to clinical features of gastric cancer patients. CGB5 primarily involves immune-related pathways, such as “Primary immunodeficiency,” “CD8 TCR signaling pathway,” and “PD-1 checkpoint signaling.”

CONCLUSION: This study demonstrates that CGB5 expression is closely associated with immune cell infiltration across cancer types, showing significant variation in infiltration patterns among tumor types. CGB5 is significantly up-regulated in various malignancies and strongly correlates with cancer patient prognoses, specifically in malignancies like GC and PAAD. Overall, these findings indicate CGB5 as a promising biomarker for pan-cancer diagnosis and prognosis.

PMID:41048937 | PMC:PMC12491329 | DOI:10.3389/fmed.2025.1624815

J Allergy Clin Immunol Glob. 2025 Jul 23;4(4):100540. doi: 10.1016/j.jacig.2025.100540. eCollection 2025 Nov.

ABSTRACT

BACKGROUND: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare inborn error of immunity caused by defects in IL-12 or IFN-γ signaling pathways, essential for intracellular pathogen control. While classically linked to nontuberculous mycobacteria, MSMD also predisposes to bacterial, fungal, and viral infections.

OBJECTIVE: We sought to provide a practical framework for diagnosing and managing MSMD in African settings. Recommendations integrate clinical evaluation, baseline immunologic testing, and molecular diagnostics.

METHODS: A review of clinical presentation, diagnostic strategies, and therapeutic approaches was conducted, emphasizing applicability in resource-limited environments.

RESULTS: MSMD presents across a wide clinical spectrum that includes severe disseminated early-onset infections and localized later-onset disease. While classically characterized by increased susceptibility to nontuberculous mycobacteria, MSMD also predisposes to bacterial, fungal, and viral infections. Standard immunologic screening often yields unremarkable findings, necessitating a tiered diagnostic approach that includes molecular testing for confirmation. Long-term antimicrobial therapy remains the cornerstone of management, with prophylaxis warranted in recurrent or severe cases. Early identification significantly reduces morbidity and mortality. Molecular diagnostic methods facilitate genotype-guided management, enabling precision medicine approaches in this context.

CONCLUSION: Timely recognition of MSMD, particularly in tuberculosis-endemic settings, is critical to prevent severe disease progression. A structured diagnostic algorithm, combined with molecular testing and individualized treatment strategies, enhances outcomes. MSMD underscores the significance of genotype-driven management.

PMID:41048447 | PMC:PMC12492193 | DOI:10.1016/j.jacig.2025.100540

Orphanet J Rare Dis. 2025 Oct 3;20(1):500. doi: 10.1186/s13023-025-03942-7.

ABSTRACT

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by pathogenic ATM gene variants, characterised by progressive cerebellar ataxia, telangiectasia, immunodeficiency, and cancer predisposition. While its immunological and oncological complications are well-documented, clinical heterogeneity, particularly in cases with elevated IgM, poses diagnostic challenges.

METHODS: Following written informed consent, we retrospectively analysed four pediatric A-T patients followed in our clinic. Clinical, laboratory, and radiological data were reviewed, including immunoglobulin levels, vaccine antibody responses, lymphocyte subsets, and alpha-fetoprotein (AFP) levels. Diagnosis was established based on clinical and laboratory findings, supported by whole-exome sequencing (WES) and targeted ATM gene sequencing.

RESULTS: Our findings further support the association between the hyper-IgM phenotype and increased immune dysfunction in A-T. We report the first globally documented case of lupus vulgaris in an A-T patient and identify a previously unreported ATM variant in our country, expanding the disease spectrum. These findings highlight the need for further research on regional genetic variations and their clinical implications.

CONCLUSION: This study highlights the importance of early diagnosis and genetic testing, particularly in atypical presentations. The recognition of novel infectious and autoimmune associations, along with novel variants, underscores the necessity of comprehensive, multidisciplinary follow-up and regional genetic screening efforts.

PMID:41044616 | DOI:10.1186/s13023-025-03942-7

Clin Exp Immunol. 2025 Oct 3:uxaf066. doi: 10.1093/cei/uxaf066. Online ahead of print.

ABSTRACT

Children with recurrent infections present a diagnostic challenge due to the wide overlap between normal childhood infections and primary immunodeficiency diseases (PIDs). Predominantly antibody deficiencies (PADs) are the most common category of PID in this population. While many PAD cases are identified through markedly low immunoglobulins levels or reduced B cell counts, some demonstrate subtler forms such as IgG subclass deficiency (IGGSD) or specific antibody deficiency (SAD), which may present similar clinical symptoms but normal standard laboratory parameters. Diagnosing these conditions in children is particularly challenging due to the overlap with physiological immune immaturity and the high incidence of infections in early childhood. Clinicians must carefully distinguish between benign infection patterns and true immunodeficiencies to avoid missed diagnoses and unnecessary investigations. This review summarizes key findings on IGGSD and SAD, highlights their clinical relevance in paediatric practice, and evaluates current challenges in diagnosis and classification. We also discuss the overlap between these conditions and propose a structured approach to improve diagnostic consistency. Addressing these knowledge gaps is essential to optimize care for children with recurrent infections and suspected antibody deficiencies.

PMID:41039842 | DOI:10.1093/cei/uxaf066

Rev Alerg Mex. 2025 Sep 30;72(3):100. doi: 10.29262/ram.v72i3.1542.

ABSTRACT

INTRODUCTION: In allergic patients with recurrent respiratory infections, the association of antibody deficiencies, both selective and specific to polysaccharide responses, has been described.

CASE REPORT: Male, no significant family history. At age 5, presented with cervical and axillary lymphadenopathy; biopsy ruled out malignancy, followed by remission. At age 7, developed nasal symptoms and wheezing. Admitted to Allergy at age 9 and diagnosed with asthma and rhinitis, sensitized to dust mites and grass. Good response to immunotherapy in the first 2 years; during the third year, developed recurrent respiratory and gastrointestinal infections every 15 days. At age 13, further workup was decided. Physical Examination: Weight 69 kg, height 1.7 m, obstructive turbinates, central bifid uvula, grade I tonsils, no lymphadenopathy, cardiopulmonary system unremarkable. Studies: Hemoglobin 15.6 g/dL, Hematocrit 46%, WBC 4005/μL, Lymphocytes 1200/μL (20%), Eosinophils 210/μL (3.6%), Platelets 219,000/μL. Low IgA 23 mg/dL (45-236), low IgM 27 mg/dL (52-242), IgE 11.9 IU/mL (≤3100), normal IgG 1060 mg/dL (560-1760), reconfirmed. Flow cytometry normal with normal B lymphocytes. Pneumococcal polysaccharide vaccine challenge showed adequate response to only 4 serotypes (<50% response). Management: Temporary treatment with prophylactic antibiotics and immunostimulants, with improvement in infectious episodes. Currently off prophylaxis. Discussion: Adolescent with quantitative IgA and IgM deficiency, currently normal IgG levels but impaired response to polysaccharide vaccine. Maintained under immunological surveillance due to potential progression to common variable immunodeficiency.

CONCLUSION: Recurrent or invasive infections in treated asthma patients warrant investigation for antibody deficiency.

PMID:41037725 | DOI:10.29262/ram.v72i3.1542