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Transl Cancer Res. 2025 Dec 31;14(12):8418-8431. doi: 10.21037/tcr-2025-1255. Epub 2025 Dec 19.

ABSTRACT

BACKGROUND: Neuroblastoma (NB) is an embryonic cancer arising from neural crest cells. Long non-coding RNA (lncRNA) plays an important role in the development of tumors. Several studies have reported that LINC01296 and thyroid hormone receptor interacting protein 13 (TRIP13) acts as oncogenic regulators of cancer. However, their deep specific biological mechanisms in tumor metastasis are not known. Here, we aimed to elucidate whether LINC01296 or TRIP13 drives NB proliferation and progression, and to assess their potential as therapeutic targets.

METHODS: In this study, we utilized the NB cell line SK-N-SH to investigate the roles of LINC01296 and TRIP13 by bacterial transformation and polymerase chain reaction (PCR) verification. Cells were infected with lentivirus, and fluorescence expression was monitored. Total RNA was extracted for reverse transcription quantitative PCR (RT-qPCR). Cell proliferation was assessed by using Cell Counting Kit-8 (CCK-8) assay. Migration was evaluated using wound-healing assays, and invasion was tested via Transwell with Matrigel-coated chambers. Apoptosis was analyzed by flow cytometry. For in vivo studies, non-obese diabetic/severe combined immunodeficiency (NOD/scid) mice were subcutaneously injected with 1×10⁷ cells/mL suspended in Matrigel. Tumor growth was measured every 2 days for 23 days; tissues were harvested for paraffin sections or stored at -80 ℃. Immunohistochemistry (IHC) involved antigen retrieval, blocking with 5% normal serum, primary antibody incubation, and counterstaining. Confocal microscopy was used for imaging.

RESULTS: In this study, we found that compared with negative control (NC) group, overexpression of LINC01296 (OE-LINC01296) or TRIP13 (OE-TRIP13) both promoted the proliferation, migration and invasion of SK-N-SH cells, while inhibiting apoptosis; and vice versa. In addition, we further demonstrated that LINC01296 stabilised knockdown via short hairpin RNA (shRNA) (sh-LINC01296) + OE-TRIP13, and TRIP13 stabilised knockdown via shRNA (sh-TRIP13) + OE-LINC01296 decreased SK-N-SH cell proliferation, migration and invasion, while promoting apoptosis. We also established a subcutaneous transplantation tumor model in NB NOD/scid mice, and sh-LINC01296 or sh-TRIP13 inhibited tumor growth in mice, and the tumor growth in the sh-LINC01296 + OE-TRIP13 group and the sh-TRIP13 + OE-LINC01296 group was between the NC group and the sh-LINC01296 or sh-TRIP13 group.

CONCLUSIONS: These results suggest that LINC01296 may play a role as an oncogene in the development of tumorigenesis in NB by mediating TRIP13, and provide a marker for the prognosis of NB.

PMID:41510121 | PMC:PMC12776195 | DOI:10.21037/tcr-2025-1255

Case Reports Immunol. 2026 Jan 7;2026:1817159. doi: 10.1155/crii/1817159. eCollection 2026.

ABSTRACT

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocyte oxidative burst and may present in early life with severe or recurrent infections. We report a female infant born at 38 weeks’ gestation (birth weight 2700 g) who developed fever and presumed sepsis at 5 days of life, followed by multiple recurrent hospitalizations for febrile illness with suspected meningitis, diarrhea, dehydration, and failure to thrive. Cerebrospinal fluid (CSF) evaluations across episodes demonstrated pleocytosis with elevated protein and normal-to-low glucose, while Gram stain and CSF cultures were repeatedly negative, consistent with recurrent culture-negative meningitis. Laboratory assessment showed intermittent anemia, thrombocytosis, and episodes of significant neutropenia. Complement and immunoglobulin levels were within reference ranges, and flow cytometry demonstrated preserved T- and B-lymphocyte compartments. A flow cytometric dihydrorhodamine (DHR) oxidative burst assay was markedly abnormal (phorbol 12-myristate 13-acetate stimulation index 13%; Escherichia coli stimulation index 22.3%), supporting the diagnosis of CGD. At ~4.5 months of age, a sterile catheter urine culture grew multidrug-resistant Klebsiella pneumoniae at ≥100,000 CFU/mL with susceptibility limited to aminoglycosides; the patient was treated with amikacin 15 mg/kg/dose intravenously once daily for 10 days, with defervescence within 48 h, clinical recovery, and a repeat urine culture showing no growth. Genetic testing was not performed due to financial and social constraints, and longer-term outcomes beyond early infancy were unavailable in the record extract. This case underscores that recurrent culture-negative meningitis in early infancy should prompt evaluation for primary immunodeficiency and that early DHR testing can expedite CGD diagnosis and guide timely preventive management and specialist referral.

PMID:41509559 | PMC:PMC12776254 | DOI:10.1155/crii/1817159

J Paediatr Child Health. 2026 Jan 7. doi: 10.1111/jpc.70280. Online ahead of print.

ABSTRACT

AIM: To evaluate the diagnostic yield and clinical triage performance of a structured, multistep algorithm in children referred for suspected inborn errors of immunity (IEI) due to recurrent infections.

METHODS: This single-centre study included 705 children (0-18 years) referred for recurrent infections. All were screened using JMF and/or MENA criteria. Of these, 132 met at least one criterion and underwent stepwise immunologic evaluation, including advanced testing when indicated.

RESULTS: Of 705 children referred with recurrent infections, 132 (18.7%) met screening criteria and underwent structured immunologic evaluation. Inborn errors of immunity were diagnosed in 50 patients (7.1%), with a 71% diagnostic confirmation rate. Pathogenic variants were detected in 74%, immunoglobulin abnormalities in 78% and all showed lymphocyte subset disturbances. The most common classifications were antibody deficiencies (32%) and syndromic combined immunodeficiencies (28%). Half received intravenous immunoglobulin, and no mortality occurred during follow-up.

CONCLUSION: The structured diagnostic algorithm based on JMF and MENA criteria improved IEI diagnosis and enabled effective prioritisation of children presenting with non-infectious immune phenotypes. This model reduced unnecessary testing, supported efficient allocation of limited resources and facilitated timely diagnosis. The approach offers a practical, cost-effective solution particularly applicable in regions with high consanguinity rates and limited access to advanced immunologic diagnostics.

PMID:41498369 | DOI:10.1111/jpc.70280

J Orthop. 2025 Dec 12;73:177-183. doi: 10.1016/j.jor.2025.12.023. eCollection 2026 Mar.

ABSTRACT

INTRODUCTION: Total hip (THA) and knee arthroplasty (TKA) are widely successful procedures but remain susceptible to complications. Patients with primary immunodeficiency (PI) conditions may face increased postoperative risks, though data is limited. This study evaluated postoperative outcomes after THA and TKA in PI patients, hypothesizing higher complication rates compared with matched controls.

METHODS: A retrospective cohort study was conducted using the PearlDiver Mariner database (2010-2020). Patients undergoing primary THA or TKA were identified by CPT codes and matched 1:1 by age, sex, and Charlson Comorbidity Index, obesity, tobacco use, alcohol abuse, and osteoarthritis. Patients with PI conditions were identified with a comprehensive list of International Classification of Diseases (ICD) 9/10 codes. Postoperative complications were assessed at 90 days, 1 year, and 2 years. Multivariable logistic regression was used to identify independent associations with PI status.

RESULTS: After 1:1 matching, PI patients had significantly higher 90-day postoperative incidence of deep vein thrombosis (DVT), pneumonia, urinary tract infection (UTI), and any complication following THA. At 1 year, PI patients were found to have increased odds of periprosthetic joint infection (PJI), DVT, acute kidney injury (AKI), pneumonia, UTI, and any complication. 2 years postoperatively, PI was associated with increased odds of PJI revision. Within 90 days of TKA, PI patients displayed a higher incidence of surgical site infection (SSI), AKI, wound disruption, pneumonia, UTI, readmission, and any complication. After one year, PI patients had higher rates of PJI, SSI, DVT, AKI, wound disruption, pneumonia, UTI, readmission, and any complication. At 2 years follow up, there were no significant differences between groups.

CONCLUSIONS: In patients undergoing THA and TKA, PI was associated with significantly higher odds of infectious and medical complications, despite lower overall rates of metabolic comorbidities. These findings highlight the need for PI-specific perioperative protocols to improve both clinical outcomes and economic benefits.

PMID:41497825 | PMC:PMC12767844 | DOI:10.1016/j.jor.2025.12.023

Medicine (Baltimore). 2026 Jan 2;105(1):e46420. doi: 10.1097/MD.0000000000046420.

ABSTRACT

RATIONALE: Griscelli syndrome (GS) is a rare autosomal recessive disorder marked by partial oculocutaneous albinism, immunodeficiency, and neurological issues. It has 3 types based on genetic mutations. This report focuses on a patient with GS type 2, characterized by immune abnormalities and neurological symptoms, with only 160 cases documented globally.

PATIENT CONCERNS: A 1-year-old boy presented with hyperthermia, diarrhea, and vomiting, revealing hypopigmented skin and silvery-gray hair. He exhibited tachycardia, abdominal distension, hepatosplenomegaly, and signs of immunocompromise. Neurologically, he showed developmental delays and hyperreflexia. Lab tests indicated anemia, thrombocytopenia, and elevated triglycerides.

DIAGNOSES: Based on clinical history and laboratory tests diagnosed with GS type 2.

INTERVENTIONS AND OUTCOMES: The patient received symptomatic treatment, antibiotics, and frequent transfusions, with strict infection prevention due to limited resources for stem cell transplantation.

LESSONS: GS, identified in 1978, is a rare autosomal recessive disorder marked by partial albinism and immunodeficiency, with around 160 cases primarily from the Mediterranean. It comprises 3 types: GS1, GS2, and GS3, each with unique genetic and clinical features. GS1 exhibits partial albinism and neurological issues without immune effects due to MYO5A mutations. GS2 presents severe immunodeficiency and risks such as hemophagocytic lymphohistiocytosis linked to RAB27A mutations. GS3, caused by melanophilin gene mutations, has a better prognosis. Diagnosis involves hair microscopy and genetic testing, and while supportive treatments exist, early diagnosis is vital for improved outcomes. GS is a rare genetic disorder with varied symptoms, categorized into 3 types, requiring genetic testing for diagnosis and treatment ranging from management to stem cell transplantation.

PMID:41496009 | DOI:10.1097/MD.0000000000046420

J Clin Immunol. 2026 Jan 6. doi: 10.1007/s10875-025-01972-1. Online ahead of print.

ABSTRACT

Patient-reported outcomes are critical to multidisciplinary, patient-centred approaches in diseases requiring lifelong management. Among inborn errors of immunity (IEIs), reports on this subject are typically limited to specific diagnostic subgroups or focus narrowly on the route of immunoglobulin replacement therapy (IgRT), offering a restricted perspective. We aimed to evaluate the health-related quality of life (HRQoL) and IgRT-related treatment satisfaction (TS) of a heterogeneous cohort of IEI patients and identify factors influencing these outcomes to guide improving the health and well-being of IEI patients. We conducted a cross-sectional survey targeting IEI patients on IgRT, assessing TS (TSQM-9) and HRQoL (KINDL/SF-36). Patient/caregiver-reported data were integrated with clinical data to identify outcomes and influencing factors. The survey included 500 IEI patients (356 children, 144 adults) diagnosed 54% Primary Antibody Deficiency (PAD), 36% combined immunodeficiency, 7% immune-dysregulation, and 3% other IEIs. Non-PAD diagnoses, comorbidities, absence of school/work attendance, and IgRT-related systemic adverse reactions negatively impacted HRQoL. Severe infections and related hospitalizations adversely influenced both HRQoL and TS. The subcutaneous route of IgRT, particularly at home, was associated with higher TS due to its convenience and reduced school/work absenteeism. However, the IgRT route did not influence adult HRQoL. Patient-reported well-being and satisfaction in IEIs are multifactorial and cannot be solely attributed to the route of IgRT. Minimizing negative experiences related to the disease or its treatment and, where possible, encouraging patients to maintain school/work attendance or engage in activities that promote societal participation can enhance self-esteem, coping abilities, and overall well-being.

PMID:41493669 | DOI:10.1007/s10875-025-01972-1

Front Dent. 2025 Sep 13;22:37. doi: 10.18502/fid.v22i37.19830. eCollection 2025.

ABSTRACT

Myelodysplastic syndrome (MDS) is a bone marrow clonal stem cell disorder characterized by the inability of immature blood cells to mature. Oral squamous cell carcinoma (OSCC) has not been previously reported in MDS patients without underlying diseases. We present a case of poorly differentiated OSCC in a 27-year-old patient with MDS. A literature review revealed 11 case reports about solid tumors in different organs of MDS patients. Among these, 5 articles reported head and neck carcinoma but none of them reported oral cancer in MDS patients. MDS predisposes patients to hematopoietic and non-hematopoietic malignancies. The oral cavity is one of the critical sites that needs to be examined periodically and regularly in MDS patients to detect OSCC in its early stages.

PMID:41492562 | PMC:PMC12765349 | DOI:10.18502/fid.v22i37.19830

Eur J Med Res. 2026 Jan 5. doi: 10.1186/s40001-025-03709-7. Online ahead of print.

ABSTRACT

BACKGROUND: USP39 is involved in mRNA splicing and stress responses. This study analyzed USP39 expression and its clinical relevance in sepsis, aiming to provide a novel treatment target for sepsis.

METHODS: The RNA-seq datasets were used for analyzing the expression profile and clinical significance of USP39 in both sepsis and control groups. Functional pathway enrichment was performed using GSEA and GSVA with the clusterProfiler package (3.14.3). Immune infiltration was evaluated via single-sample GSEA (ssGSEA). The prognostic value of USP39 was assessed utilizing Cox regression, and its diagnostic performance was determined via receiver operating characteristic (ROC) curve analysis employing the survival (3.5.7) and pROC (1.18.5) packages, respectively. For single-cell RNA-seq (scRNA-seq) data (GSE175453), we performed quality control, normalization, principal component analysis (PCA), batch correction, clustering, and Uniform Manifold Approximation and Projection (UMAP) visualization employing the Seurat 4.4.0 package. THP-1 cells were treated with lipopolysaccharide (LPS) to mimic septic injury. USP39 was overexpressed via pcDNA3.1 transfection. Cellular assays were conducted to measure cell viability, apoptosis, and inflammatory cytokines (IL-1β, IL-6, TNF-α).

RESULTS: Our study found that USP39 was significantly downregulated in sepsis patients and was associated with age, diabetes, and Intensive Care Unit (ICU)-acquired infections. Functional enrichment analysis revealed that high USP39 expression was linked to metabolic processes, primary immunodeficiency, and spliceosome, and immune response and inflammation pathway. In addition, USP39 also exhibited a high diagnostic value and was identified as an independent prognostic marker in sepsis. ssGSEA revealed higher infiltration of CD8⁺ T cells, activated B cells, and CD4⁺ T cells in the high USP39 expression group, while Th17 and NK cells were more abundant in the low USP39 expression group. According to the results of scRNA-seq analysis, USP39 exhibited significant differential expressions in monocytes and T cells, with low expression observed in sepsis. Furthermore, in vitro experiments confirmed that overexpression of USP39 significantly enhanced cell viability and suppressed apoptosis in LPS-induced THP-1 cells while also inhibiting the expression of inflammatory cytokines.

CONCLUSION: The significant downregulation of USP39 was correlated with both clinical features and immune infiltration in sepsis, highlighting its role in immune regulation and its potential as a prognostic biomarker.

PMID:41491968 | DOI:10.1186/s40001-025-03709-7

Pharmazie. 2025 Dec 1;80(11):156-160. doi: 10.1691/ph.2025.5665.

ABSTRACT

Since many years, immunoglobulin G (IgG) substitution has been used to treat patients with primary immunodeficiencies (PID) to reduce the number of infections and the burden of disease. Nevertheless, many patients continue to suffer from persisting infections. In this SINUS study, a patient questionnaire consisting of 21 questions was used to assess the current situation in patients with PID. Of the 160 patients included, most showed a persistent tendency to infections (N=140, 87.5%). During the last 12 month, most of the patients suffered from upper and lower respiratory tract infections such as sinusitis (N=85, 60.7%), bronchitis (N=88, 62.9%), and pneumonia (N=10, 7.1%). Yet the presence of persistent infections was not inversely correlated with patient satisfaction. Therefore, the treating physicians need to carefully evaluate the infection history and additional therapeutic approaches are required for satisfying improvement in the patient’s infection control. Patients are open to explore new ways to achieve this goal.

PMID:41491392 | DOI:10.1691/ph.2025.5665

J Clin Invest. 2025 Nov 4;136(1):e196381. doi: 10.1172/JCI196381. eCollection 2026 Jan 2.

ABSTRACT

NK cells, or natural killer cells, might be interesting players to investigate further in the disease process of patients with deficiency of ADA2, a rare, recently discovered inborn error of immunity.

PMID:41480770 | DOI:10.1172/JCI196381