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BMC Cancer. 2025 Jun 5;25(1):1005. doi: 10.1186/s12885-025-14211-y.

ABSTRACT

BACKGROUND: Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon cancer who experienced explosive tumor growth. A clinical multidisciplinary team (MDT) collaborated with bioinformaticians to provide precise treatment and elucidate the biological mechanisms underpinning this growth.

METHODS: A 28-year-old male patient diagnosed with colon cancer experienced explosive tumor growth. Peripheral bloods (PB) during immunotherapy were collected for immune cytokine analyses and flow cytometry assays on immune cell subsets. To further examine the underlying mechanisms of this explosive-growth, we conducted whole exome sequencing (WES) and RNA-sequencing (RNA-seq) of samples taken at different time points.

RESULTS: The patient was diagnosed with Lynch syndrome. We implemented an immunotherapy and performed PB immune cytokine assays before, during, and after this therapy. Our observations suggested that immunotherapy may remodel interferon-gamma (IFN-γ) signaling and enhance T cell-mediated immune responses. By exploring explosive tumor growth mechanisms, we observed that tumors had significantly less insertion and deletion (INDEL) mutations and INDEL-derived neoantigens. Additionally, they had deficient antigen presentation functions as characterized by decreased IFN-γ signaling activity.

CONCLUSIONS: Neoantigen loss and decreased IFN-γ signaling activity contributed to explosive tumor growth in this patient. Recovered IFN-γ signaling may lead to effective immunotherapy outcomes.

PMID:40474074 | DOI:10.1186/s12885-025-14211-y

Microb Pathog. 2025 Jun 3:107776. doi: 10.1016/j.micpath.2025.107776. Online ahead of print.

ABSTRACT

Fungal infections, which affect approximately one billion people worldwide, pose significant health challenges due to their unique eukaryotic cell structures, requiring specialized treatments. Common fungal infections, such as dermatophyte-related conditions, vary from superficial to severe. Their prevalence is increasing due to factors like immunosuppression and acquired immunodeficiency syndrome (AIDS). While topical treatments are the primary approach, they often encounter limitations such as poor skin penetration. Additionally, conventional formulations require high doses and frequent administration. Recent advancements, including novel carriers, aim to overcome these challenges and reduce local side effects. This review highlights the innovations in transdermal drug delivery systems for antifungal agents, focusing on azoles, polyenes, echinocandins, allylamines, and other antifungal agents. Innovative delivery technologies, such as liposomes, microneedles, and microemulsions, are underscored to enhance skin permeation, improve drug stability, and ensure sustained release. The review emphasizes the improved efficacy and antifungal activity of these systems compared to traditional methods. It also addresses their safety and clinical potential, offering new strategies to improve treatment outcomes for fungal skin infections.

PMID:40473124 | DOI:10.1016/j.micpath.2025.107776

Cureus. 2025 May 5;17(5):e83507. doi: 10.7759/cureus.83507. eCollection 2025 May.

ABSTRACT

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare and complex primary immunodeficiency disorder. The classic clinical triad of APS-1 includes chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Clinically, APS-1 presents with significant variability and is characterized by autoimmune dysfunction affecting both endocrine organs (including the parathyroids, adrenal glands, thyroid, gonads, and pituitary) as well as non-endocrine tissues (such as the skin, liver, kidneys, lungs, eyes, and intestines). Here we present a 23-year-old female with a history of abnormal body movement associated with posturing and transient loss of consciousness, along with a history of recurrent oral ulceration, itchy patches over intertriginous areas, and pigmentation of skin. Her examination was suggestive of low blood pressure, oral and cutaneous candidiasis, and hyperpigmentation of the skin. Routine investigations showed very low serum calcium, low parathyroid hormone (PTH) levels, and low early morning cortisol levels, and pathological calcification of the basal ganglia was noted on CT brain. As the patient met the diagnostic criteria of APS-1, she was treated accordingly and responded well.

PMID:40470404 | PMC:PMC12135895 | DOI:10.7759/cureus.83507

Front Cell Infect Microbiol. 2025 May 21;15:1570382. doi: 10.3389/fcimb.2025.1570382. eCollection 2025.

ABSTRACT

OBJECTIVES: This study aimed to analyze the clinical characteristics and genetic features of children with adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine. The goal was to improve understanding of this condition, provide insights into early diagnosis and intervention, and support stratified management.

METHODS: Clinical data of 35 children hospitalized at Kunming Children’s Hospital between January 2014 and June 2024 with complete records and diagnosed with BCG vaccine adverse reactions were collected. Cases were classified into two groups: disseminated BCG disease (BCG-D) and BCG-itis. Children with primary immunodeficiency (PID) were further divided into severe combined immunodeficiency (SCID) and non-SCID groups. Clinical characteristics, immunological profiles, genetic backgrounds, and outcomes were compared between the groups.

RESULTS: Among the 35 cases, 25 were male, and 10 were female, with a median age of onset of 2 months (1-4 months). Eight cases (22.9%) were diagnosed with BCG-D, while 27 cases (77.1%) were classified as BCG-itis. Sixteen cases (45.7%) were confirmed to have PID, including SCID (7 cases, 20.0%), chronic granulomatous disease (6 cases, 17.1%), Mendelian susceptibility to mycobacterial disease (2 cases, 5.7%), and fas associated via death domain (FADD) gene mutation (1 case, 2.6%). Compared to the BCG-itis group, the BCG-D group exhibited significantly higher rates of fever, hepatosplenomegaly, elevated white blood cell counts, neutrophil counts, and C-reactive protein (CRP) levels, along with lower red blood cell counts and hemoglobin levels (p<0.05). Similarly, the SCID group showed significantly lower age, lymphocyte counts, IgM levels, CD3, CD4, and CD8 cell ratios, but higher CD19 cell ratios and mortality rates compared to the non-SCID group (p<0.05). Twenty-seven (77.1%) cases were discharged after improvement, and eight children (22.9%) succumbed to the condition, including six with SCID gene mutations (representing 85.7% of the total SCID cases), one with an interleukin 12 receptor subunit beta 1(IL12RB1) mutation, and one who was not genetically tested but diagnosed with disseminated BCG disease.

CONCLUSIONS: In children presenting with adverse reactions to the BCG vaccine, the presence of fever, hepatosplenomegaly, elevated neutrophil levels, and CRP should prompt evaluation for disseminated BCG disease and assessment of immunological status. Early identification of underlying PID, particularly SCID, is crucial, given the high mortality and poor prognosis associated with the condition, necessitating timely interventions.

PMID:40470261 | PMC:PMC12133749 | DOI:10.3389/fcimb.2025.1570382

Cutan Ocul Toxicol. 2025 Jun 4:1-9. doi: 10.1080/15569527.2025.2511721. Online ahead of print.

ABSTRACT

PURPOSE: Primary immune deficiencies (PIDs) can present with a wide range of clinical findings. This review aims to evaluate PIDs in which cutaneous findings are common.

MATERIALS AND METHODS: English literature regarding cutaneous manifestations of primary immunodeficiencies was reviewed using PubMed between January 2005 and March 2023.

RESULTS: Cutaneous findings in PIDs can be broadly classified into two main groups: infectious and non-infectious. The most prevalent skin finding in PIDs is cutaneous infections (bacterial, fungal, and viral), and these infections often manifest as early-onset, recurrent, treatment-resistant, or atypical cases. Eczema is being the most frequent among non-infectious findings. Cutaneous manifestations, such as erythroderma, telangiectasia, granulomatous dermatitis, and autoimmune symptoms like alopecia and vitiligo can also occur.

CONCLUSION: Cutaneous manifestations in PIDs can assist clinicians in making early diagnoses, enabling patients to receive appropriate therapy promptly.

PMID:40465559 | DOI:10.1080/15569527.2025.2511721

Front Biosci (Landmark Ed). 2025 May 20;30(5):27231. doi: 10.31083/FBL27231.

ABSTRACT

Inborn errors of immunity (IEIs) are a group of more than 485 disorders that impair immune development and function with variable reported incidence, severity, and clinical phenotypes. A subset of IEIs blend increased susceptibility to infection, autoimmunity, and malignancy and are known collectively as primary immune regulatory disorders (PIRDs). Programmed cell death, or apoptosis, is crucial for maintaining the balance of lymphocytes. Genetic-level identification of several human inherited diseases with impaired apoptosis has been achieved, such as autoimmune lymphoproliferative syndrome (ALPS), caspase-8 deficiency state (CEDS), X-linked lymphoproliferative syndrome (XLP), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway disorders. The consequences of this disease are manifested by abnormal lymphocyte accumulation, resulting in clinical features such as lymphadenopathy, hepatomegaly, splenomegaly, and an increased risk of lymphoma. Additionally, these disorders are often associated with autoimmune disease, particularly involving blood cells. Understanding the molecular pathogenesis of these conditions has provided critical insights into the signaling pathways that regulate apoptosis and lymphocyte activation, shedding light on mechanisms of immune dysregulation. This review focuses on the intersection between apoptosis, autoimmunity, and lymphoproliferation, discussing how dysregulation contributes to the development of these immune disorders. These conditions are characterized by excessive lymphocyte accumulation, autoimmunity, and/or immunodeficiency. Understanding their molecular pathogenesis has offered new insights into the signaling mechanisms that regulate apoptosis and lymphocyte activation.

PMID:40464495 | DOI:10.31083/FBL27231

Orphanet J Rare Dis. 2025 Jun 3;20(1):270. doi: 10.1186/s13023-025-03749-6.

ABSTRACT

BACKGROUND: The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity-sharing manifestations including increased infection susceptibility, eczema, and raised serum IgE. Pulmonary complications are responsible for high morbidity and mortality rates in patients with HIES. This study examines the progression of pulmonary disease in adult patients with HIES and compares the subsequent findings with existing literature.

METHODS: Ten adult patients with HIES diagnosed at Peking Union Medical College Hospital (PUMCH) from January 2016 to October 2023 were included in this study. Diagnosis was confirmed using the National Institutes of Health (NIH) criteria and whole-exome sequencing. Clinical data on pulmonary disease progression, microbiology, imaging and histology were collected. A systematic literature review was conducted for comparison.

RESULTS: Recurrent pulmonary infections led to significant structural lung damage, with 90.0% (9/10) of patients developing bronchiectasis and pneumatocele. Early infections (0-10 years) were predominantly due to Staphylococcus aureus (80.0%,8/10), while later stages (6-22 years) showed a shift to more complex infections with Aspergillus/fungus (70.0%,7/10), Mycobacterium tuberculosis (50.0%, 5/10), and Pseudomonas aeruginosa (40.0%, 4/10). Imaging revealed extensive bronchiectasis and pneumatocele formation. Histological examinations demonstrated acute inflammation (40%, 2/5), granuloma formation (80%, 4/5), and eosinophilic infiltration (100%, 5/5). Comparatively, our findings are consistent with previous reports that suggest a higher incidence of pulmonary structural damage in patients with the signal transducer and activator of the transcription 3 (STAT3) mutations than in those with other gene variants. However, our cohort showed a faster progression from initial infection to structural damage, highlighting the need for early intervention.

CONCLUSION: The progression of pulmonary disease in HIES patients underscores a critical three-step process: initial recurrent infections, development of structural lung damage, and subsequent reinfections that aggravate the damage. This rapid transition from infection to structural damage, especially in patients with STAT3 mutations, highlights the importance of early and aggressive intervention. Managing reinfections after structural lung damage is essential to prevent further deterioration and to improve long-term outcomes.

PMID:40462219 | DOI:10.1186/s13023-025-03749-6

J Fish Dis. 2025 Jun 3:e14145. doi: 10.1111/jfd.14145. Online ahead of print.

ABSTRACT

Schizothorax prenanti is an important economic Cyprinidae fish endemic to the upper reaches of the Yangtze River in China. The wild population of S. prenanti continues to decline and has been listed as an endangered fish because of environmental pollution and overfishing. Herein, the skin cell line (SPSK) of S. prenanti was established using the tissue block method to aid in protecting S. prenanti at the cellular level and provide a skin cell line that can be applied in functional genomics and disease aetiology of the spring viraemia of carp virus (SVCV), which is highly infectious in Cyprinidae fish. The SPSK cell line was sub-cultured to more than 30 generations at 24°C in L-15 medium supplemented with 15% fetal bovine serum (FBS). Karyotype analysis further revealed that the chromosome number of SPSK ranged between 140 and 149, with 146 accounting for the highest proportion. Significant fluorescent signals were observed after transfection of SPSK with pEGFP-N1 and Cy3-siRNA, with a 30% and 90% transfection efficiency, respectively. Severe cytopathic effects (CPE) were also observed when SPSK was infected with SVCV, and the SVCV glycoprotein gene was detected by RT-PCR, indicating that SPSK was susceptible to SVCV. To further explore the mechanism of bacterial infection, transcriptome analysis was conducted for LPS treated SPSK cells and 9099 differentially expressed genes were identified. These genes significantly enriched into pathways including the Haematopoietic Cell Lineage and Primary immunodeficiency. Furthermore, seven predominantly expressed epidermal maker genes were identified by transcriptomic data, suggesting that SPSK cells were mainly derived from skin epidermis, composed of epidermal stem cell, Merkel cell, and immune cell. The establishment and characterisation of SPSK revealed its application in functional genomics and aetiology studies, making it a favourable tool for exploring disease control in S. prenanti and recovering fish resources.

PMID:40459177 | DOI:10.1111/jfd.14145

Front Immunol. 2025 May 19;16:1549768. doi: 10.3389/fimmu.2025.1549768. eCollection 2025.

ABSTRACT

Severe Combined Immunodeficiency (SCID) is a widely underdiagnosed congenital disease that is fatal by 2-years old if left untreated. Most cases of SCID are diagnosed from the prompting of family history while other cases are sporadic and have no indicators for diagnosis besides the onset of debilitating infections. T-cell Receptor Excision Circle Newborn Screening (TREC NBS) offers an accessible way of flagging for SCID and other T-cell lymphopenia; however, the test implementation rate is low, particularly in Asian countries. This review of the literature will explore the significance of TREC NBS for diagnosing SCID with a focus on the potential impact of widespread implementation on infant healthcare in Southeast and East Asian countries including South Korea, Japan, China, Mongolia, Taiwan, Malaysia, Singapore, and Thailand.

PMID:40458401 | PMC:PMC12127307 | DOI:10.3389/fimmu.2025.1549768

Pediatr Int. 2025 Jan-Dec;67(1):e70085. doi: 10.1111/ped.70085.

ABSTRACT

PURPOSE: Severe combined immunodeficiency (SCID) is a pediatric emergency, and rapid genetic diagnosis is necessary for proper patient management, leading to successful stem cell transplantation and gene therapy. Ataxia telangiectasia (AT) requires early diagnosis to prevent infectious diseases and early detection of cancer. We aimed to diagnose patients with SCID/AT as quickly as possible and link them to the best treatments via the primary immunodeficiency database in Japan (PIDJ) network.

METHODS: For 111 patients with suspected combined immunodeficiency, including SCID/AT, we analyzed T-cell receptor excision circle (TREC) and sequenced 29 causative genes of SCID, including ATM, by ion semiconductor sequencing using multiplex polymerase chain reaction amplicons. In some cases, DNA extracted from dried blood spots was used for the analysis.

RESULTS: Approximately 70.8% of 0-1-year-old patients and 26.5% of the patients >2 years old with low TREC were diagnosed genetically, including ADA, ATM, IL2RG, IL7R, JAK3, RAG1, RAG2, DCLRE1C, NHEJ1, and LIG4. However, only 6.9% of patients with normal TREC were genetically diagnosed (STIM1 and ATM) in our panel. In Japan, all patients had been genetically diagnosed after infection or other life-threatening conditions, and >80% of patients are linked to appropriate treatment after diagnosis.

CONCLUSIONS: Target gene sequencing, including SCID and AT genes, was useful for the diagnosis of patients with combined immunodeficiency with low TREC and to lead them to prompt treatment and better prognosis.

PMID:40457861 | DOI:10.1111/ped.70085