Omenn syndrome is a rare form of severe combined immunodeficiency characterized by immune dysregulation, recurrent infections, erythroderma, eosinophilia, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) remains the definitive treatment; however, outcomes are particularly challenging in patients with active severe infections before transplantation. Here, we report the case of a female infant who presented with persistent diarrhea and recurrent otitis media at 2 months of age and was diagnosed at 3 months with genetically confirmed Omenn syndrome caused by a homozygous pathogenic RAG1 variant (c.1187G>A; p.Arg396His). Her clinical course was complicated by recurrent multidrug-resistant bacterial bloodstream infections, Candida auris fungemia, acute kidney injury, disseminated intravascular coagulation, and respiratory failure requiring pediatric intensive care admission. Because she was clinically unstable for conventional conditioning chemotherapy, she underwent unconditioned matched unrelated donor peripheral blood stem cell transplantation at 8 months of age. Despite persistent mixed donor chimerism and absent Bcell engraftment, she demonstrated progressive donor-derived T-cell recovery, normalization of CD4/CD8 ratio, resolution of recurrent infections, and sustained clinical stability. To our knowledge, reports describing unconditioned matched unrelated donor HSCT in genetically confirmed Omenn syndrome complicated by multidrug-resistant bacterial infections and Candida auris fungemia remain extremely limited. This case highlights that unconditioned HSCT may provide clinically meaningful immune reconstitution when standard conditioning is not feasible.
Despite the success of single-target antigen CART therapy against CD19, there are certain limitations that need to be investigated properly to build a universal treatment for hematologic cancer. Other than CD19, there have been many reports on CD30 and CD20, which are also clinically relevant in different types of hematologic malignancies, but no reports have been published yet that target both antigens as bispecific targets on a single cell. Therefore, we developed a tandem receptor that targets dual antigens with a single receptor and likely reduces tumor marker escape mutations. In this study, we employed a gene editing strategy to disrupt TCRs and a target-specific integration of CAR receptors into T cells to develop a novel CAR model to address tumor-off-target limitations.
To support the study of Kr & uuml;ppel-like factor 2 (KLF2) regulatory mechanisms on cytotoxic T lymphocytes (CTLs), we studied a possibility with a web-based bioinformatics module that enables researchers to identify putative KLF2-binding promoter regions in genomic DNA sequences. After a KLF2 protein structure with C2H2 zinc finger domain and binding-site analysis, we successfully set up a tool to integrate Python-based sequence parsing and motif identification routines to locate CACCC motifs near potential start codons (e.g., ATG) across reading frames associated with key CTL genes such as TNF-alpha and IFN-gamma. The tool supports visualization and sequence upload functionality through a static website interface, making it accessible for researchers and clinicians investigating KLF2-mediated transcriptional control in tumor-infiltrating lymphocytes (TILs). This work supplements our primary study on spatial-temporal regulatory networks involved in TIL reactivation by KLF2 down-regulation.
Lactic acid bacteria and polyphenols are known to have various health-promoting effects. Pediococcus sp. KB1 (KB1) is a probiotic that was isolated from pickled suguki turnips and has been shown to have potential immunomodulatory activity and strong resistance to gastric acid. Rosmarinic acid (RA) is a phenolic compound commonly found in Lamiaceae plant species, known for its broad anti-inflammatory properties. However, the underlying mechanisms of the combined effects of KB1 and RA on pollinosis remain unclear. The aim of this study was to investigate the effects of oral administration of KB1 and RA on symptom amelioration and anti-inflammatory activity using a murine model of pollinosis. Our results showed that the KB1 + RA group had attenuated sneezing and nasal rubbing in our murine model of cedar pollinosis. The KB1 + RAgroup exhibited decreased serum histamine levels and reduced Cry j1-specific IgE levels. In both the KB1 and KB1 + RA groups, spleen tissue weight was significantly reduced. In addition, in the KB1 + RA group, increased mRNA expression levels of IL-10, IL-27, IFN-gamma, and Foxp3 in the spleen, along with reduced Fc epsilon RI-alpha protein expression, were found. These observations suggest that the combined administration of KB1 + RA may alleviate symptoms by regulating the Th1/Th2 balance and anti-inflammatory cytokines. These results suggest that KB1 and RA may serve as potential natural anti-inflammatory agents for the management of pollinosis.
Background/objective: CD40 ligand (CD40L/CD154), a member of the TNF superfamily, plays a critical role in immune regulation. Primarily expressed on CD4+ T cells, the CD40-CD40L interaction is essential for B-cell activation, antibody production, and isotype class switching. CD40L expression on T cells has been linked to Mycobacterium tuberculosis (MTB)-stimulated IFN-gamma production by peripheral blood mononuclear cells. This study aimed to determine the serum concentration of soluble CD40L (sCD40L) and its surface expression on CD4+ T cells in newly diagnosed tuberculosis (TB) patients and in TB patients undergoing anti-tuberculosis treatment (ATT) for 2-3 months. Materials and methods: Ninety-two subjects infected with MTB were recruited and divided into two groups; Group I consisted of 46 newly diagnosed TB patients without prior treatment, and Group II included 46 TB patients receiving ATT for the last 2-3 months. Serum sCD40L concentration of each participant was measured using ELISA, while its surface expression on CD4+ T cells was analyzed via flow cytometry. Results: Serum sCD40L levels were significantly lower in (Group I) newly diagnosed TB patients (median = 11.1 ng/mL, IQR = 1.19-20.8) compared to (Group II) patients undergoing ATT (median = 17.4 ng/mL, IQR = 8.9-27.8), with a statistically significant difference between the groups (p = 0.000). The surface expression of CD40L on CD4+ T cells was also lower in Group I (median = 2.9, IQR = 0.16-13.99) compared to Group II (median = 3.22, IQR = 0.01-12), though the difference was not statistically significant (p = 0.893). Conclusion: Newly diagnosed TB patients exhibited reduced levels of sCD40L, which increased following 2-3 months of anti-tuberculosis treatment. These findings suggest that CD40L may play a role in the immune response to tuberculosis and that its levels are modulated by treatment.
Immunotherapy has transformed cancer treatment paradigms by harnessing the body's immune system to combat malignancies. However, hypersensitivity reactions (HSRs) associated with these agents pose significant challenges in oncology nursing. This review provides an in-depth analysis of HSRs to cancer immunotherapy regarding incidence, clinical manifestations, and management, and discusses the crucial role of nurses in early detection, patient education, and supportive care. A narrative review approach was used. Literature was systematically searched in PubMed, Embase, CINAHL, and Scopus databases for studies published up to 2025, focusing on immunotherapy-related HSRs, nursing management strategies, and evidence-based care guidelines. Relevant clinical guidelines and position statements from the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and the National Comprehensive Cancer Network (NCCN) were also reviewed. Oncology nurses must be aware of HSRs and enhance their nursing practices in order to mitigate risks and optimize patient outcomes.
Extracellular vesicles (EVs) constitute a diverse group of micro- and nano- sized membranous lipid bilayer particles secreted by prokaryotic and eukaryotic cells. They are enriched with bioactive constituents, including lipids, proteins, mRNAs, and miRNAs. EVs play a crucial role in cell-cell communication and facilitate trans-membrane signaling. Particularly, plant-derived EVs exhibit excellent bioaccessibility and minimal immunogenicity and they play a significant role in maintaining cellular homeostasis. These plant vesicles are considered safe, and their efficacy in the prevention and treatment of various diseases has been well documented in preclinical studies. In this mini-review, we attempted to summarize the in vitro and in vivo research of plant EVs for skincare and regenerative management. Collectively, plant-derived EVs, including Dendropanax morbifera, Panax ginseng, Aloe vera, broccoli, Olea europaea, and Physalis peruviana, exert strong potential for depigmentation, skin protection, anti-aging, and antioxidant/anti-inflammatory effects, highlighting their promise as multifunctional bioactive agents and delivery vehicles in cosmetic and therapeutic applications. Despite the demonstrated ability of plant EVs to enter skin cells and deliver protective compounds, their utilization in the cosmetic and cosmeceutical industries is in its nascent stages. Considering their demonstrated capabilities, we emphasized the need for comprehensive clinical research and discussed the innovations, challenges, and opportunities to fully explore their potential for skincare and regenerative applications.
The transactivator of transcription (Tat) protein is a transactivative transcription factor of the Human Immunodeficiency Virus Type 1 (HIV-1) that contains multiple functional domains and exhibits diverse biological activities, including the activation of viral gene expression and the regulation of host cellular pathways. In immune cells, Tat profoundly affects the function of immune cells by inducing apoptosis, modulating immune responses, promoting inflammation, and impairing antigen presentation. In this review, we provided a comprehensive overview of Tat's molecular structure, its function, and its impact on the gene transcription of hose cells. Furthermore, the multidimensional mechanisms by which immune cells T cells, B cells, macrophages, and dendritic cells are impacted by Tat were also reviewed. We state that Tat is potentially regarded as a therapeutic target, emphasizing the importance of developing targeted intervention strategies.
Objective: Yupingfeng granules (YPFs), a traditional Chinese herbal formulation, have been widely used in managing allergic diseases; yet, their molecular mechanisms remain unclear. In this study, we aimed to determine whether YPFs alleviate pediatric asthma by modulating alternative splicing in immune-related genes. Methods: Fifty-four children with asthma were randomized to receive standard treatment with or without YPF for 30 days. Clinical outcomes were assessed using C-ACT/TRACK scores and serum IgE levels. RNA sequencing of peripheral blood lymphocytes was conducted before and after treatment to identify differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs). Correlations between key RASEs and IgE changes were analyzed. Results: YPF significantly improved asthma control and reduced serum IgE compared to standard therapy alone (p < 0.05). RNA-seq analysis identified 66 significant RASEs, mainly exon skipping events. Notably, splicing changes in CD83 and PPP2CA were strongly correlated with IgE reduction (r = 0.58 and 0.62, respectively; p < 0.05). Enrichment analysis revealed involvement of pathways such as cAMP signaling and ABC transporters. Conclusion: YPF may exert immunomodulatory effects in pediatric asthma by regulating alternative splicing of immune genes, especially CD83 and PPP2CA, thereby reducing IgE levels. These findings suggest a novel post-transcriptional mechanism for traditional herbal therapy in allergic airway disease.
In this study, we reported a rare case of Harel-Yoon syndrome (HAYOS) caused by a mutation in the ATAD3A gene on chromosome 1p36.33. A 34-day-old female infant presented with the chief complaints of "intermittent irritability and poor feeding for 8 days, worsening over the past hour." Laboratory investigations revealed hyperammonemia and lactic acidosis. Cardiac injury biomarkers and inflammatory markers were elevated. Echocardiography indicated cardiac insufficiency and cardiomyopathy. Both parents were phenotypically normal, non-consanguineous, and had no family history of inherited disorders. Further whole-exome sequencing (including mitochondrial DNA) identified a heterozygous missense variant, c.1582C>T (p.Arg528Trp), in the ATAD3A gene in the proband. This was confirmed to be a de novo variant, leading to a diagnosis of HAYOS. This variant was classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines and constitutes the genetic etiology of HAYOS in this patient. We summarized the clinical characteristics of this case and reviewed the relevant literature. This report expands the known genotype-phenotype spectrum associated with ATAD3A gene variants and enhances clinical recognition and diagnostic capabilities for this rare disorder.
Background: Long-term oral aspirin (Asp) therapy poses challenges in children with Kawasaki Disease (KD) complicated by coronary artery aneurysms (CAA), especially when frequent epistaxis is present. Objective: This study seeks to evaluate the efficacy and safety of a reduced-dose aspirin regimen for an antiplatelet therapy during the subacute and convalescent phases of KD. Methods: This retrospective study included 554 pediatric KD patients (350 males, 204 females; median age: 2.5 years). The patients were divided into two groups based on their aspirin dosage initiated one week after fever subsidence: The observation group (OG, n = 253) received low-dose Asp (1.5-2.5 mg/kg/day), while the control group (Ctrl, n = 301) received standard-dose Asp (3-5 mg/kg/day). Results: The incidence of bleeding was significantly lower in the OG compared to the Ctrl group (p < 0.05). In both groups, the coronary thrombi either shrank or resolved after one year following alteplase therapy, provided that the international normalized ratio (INR) was maintained at 2.0-3.0 and arachidonic acid (AA) inhibition remained below 20%, with no significant intergroup difference (p > 0.05). Aspirin resistance (AR) was observed in 17 OG patients, which resolved after increasing the Asp dose to 3-5 mg/kg/day for one week. Mural thrombosis occurred in six patients (3 per group), none of whom had AR. Conclusion: Reducing aspirin to a half-dose regimen after intravenous immunoglobulin (IVIG) treatment in the subacute and recovery phases of KD is both safe and effective, thereby significantly lowering the risk of bleeding without compromising the antithrombotic efficacy.
Klebsiella pneumoniae is a significant etiological agent of both community-acquired and nosocomial infections, characterized by its pronounced vulnerability to drug resistance. Preventive measures, such as vaccine research, are essential since no effective and viable vaccine currently exists. Pili, a critical virulence component in Klebsiella pneumoniae, promote bacterial adherence and have very low variability relative to other virulence factors, rendering them a viable target for vaccination. The 65.5 kDa pili protein has been recognized as a possible antigen owing to its significant antigenicity. This study sought to assess the immunogenic response by quantifying IgG, IgG1, and IgG2a levels in BALB/c mice following the delivery of the 65.5 kDa pili protein. A total of 24 mice were categorized into three groups: PBS, adjuvant, and pili. Serum concentrations of IgG, IgG1, and IgG2a were assessed via ELISA. Statistical analysis was conducted utilizing the ANOVA test with a 95% confidence interval. The data indicate that vaccination with the 65.5 kDa pili protein elicits a robust humoral immune response characterized by increased IgG and IgG1 production, suggesting a Th2-biased response, while showing no significant impact on IgG2a levels, which are typically associated with Th1-mediated immunity. In summary, the 65.5 kDa pili protein shows promise as a vaccine candidate for Klebsiellapneumoniae by inducing a strong IgG and IgG1-mediated immunological response in BALB/c mice. Future studies should use flow cytometry to assess immune cell activation, cytokine profiling for Th1/Th2 responses, and antigen-specific assays to explore T-cell activation. Research on dose optimization, adjuvant screening, immunity duration, and challenge studies with virulent Klebsiella pneumoniae is crucial. Proteomic analysis and epitope mapping can aid in refining vaccine design.
The COVID-19 global vaccination campaign was justified as a necessary exit strategy from an unprecedented public health, social, and economic crisis. However, concerns about adverse effects post-vaccination-particularly autoimmune reactions-have received comparatively less attention in the peer-reviewed literature. This protocol outlines a two-phase qualitative coding study that builds on a completed scoping review of 109 peer-reviewed articles to evaluate how associations between COVID-19 vaccination and autoimmune disorders are interpreted and framed. Accordingly, rather than adjudicating the scientific truth of vaccine-related claims, the study will examine whether interpretations are proportionate to the evidence presented and internally consistent. Phase 1 will focus on biological plausibility by extracting mechanistic explanations, such as molecular mimicry, bystander activation, and cytokine dysregulation, and assessing whether the mechanistic evidence reported aligns with authors' conclusions. Phase 2 will focus on epistemic integrity by applying a typology to analyze the evidentiary consistency between claims about vaccine-related harms and benefits within studies. Quotations will be extracted and analyzed for causal reasoning, rhetorical framing, and evidentiary symmetry. Articles will be double-coded, with inter-rater reliability assessed and adjudicated through discussion. By integrating mechanistic and epistemic analyses, the planned study will provide a framework for evaluating the interpretive standards applied to vaccine safety claims. Rather than reaffirming or rejecting specific biomedical positions, it will document how scientific knowledge is framed, qualified, or selectively emphasized-highlighting interpretive practices that have shaped evidence-based discourse within a climate of perceived urgency and institutional consensus.
This study sought to identify potential biomarkers of thyroid cancer, such as visfatin, resistin, IL-17, and IL-23 levels, alongside investigating their involvement in the progression of the disease. Methods: This study included 56 patients that have thyroid cancer and 47 healthy people whose sexes and ages were matched to the healthy group. The sandwich enzyme-linked immunosorbent assay (ELISA) kit, which is widely available and dependable, was utilized to measure the level of interleukin-17, interleukin-23, visfatin, and resistin within the serum of the patient and control groups. These biochemical values were plotted against a receiver operator characteristic (ROC) curve to determine their potential diagnostic use. Results: The serum levels of Interleukin-17 (255 +/- 25.82 pg/mL), IL-23 (461.03 +/- 29.97 pg/mL), visfatin (19.42 +/- 2.91 ng/mL), and resistin (25.3 +/- 1.9 mu g/L) were all noticeably higher in the thyroid cancer patients; the ROC analysis indicated that these serum concentrations may be used as potential biomarkers for thyroid cancer diagnoses. Conclusion: In contrast to IL-17 and IL-23, which demonstrated stronger specificities (94.1% and 83.7%, respectively) and closer associations with thyroid cancer pathogenesis, the resistin and visfatin levels were significantly elevated in patients with thyroid cancer and showed diagnostic potential in the ROC analysis (AUC > 0.8). However, their non-specific pro-inflammatory roles and wider variability in metabolic conditions (e.g., obesity, insulin resistance) may limit their reliability as early diagnostic biomarkers. Therefore, resistin and visfatin need to be further validated in bigger cohorts to evaluate the confounding impacts, while IL-17 and IL-23 may be more suited for early identification.
Psoriasis after vaccination, namely “Psoriasis Vaccinalis”, has been described with several vaccines. More recently, emerging reports have linked coronavirus (COVID-19) vaccines to exacerbation or new-onset psoriasis. We report 2 female patients who developed severe new-onset palmoplantar pustular psoriasis following vaccination against COVID-19 (one received a deactivated vaccine, and one received an mRNA vaccine). The patients developed the psoriatic lesions 1 and 2 weeks after the vaccinations, respectively. The patients were primarily diagnosed in a primary care facility or through self-diagnosis with skin/deep soft tissue infections of the hand or foot, and started topical antibiotics before seeking dermatological consultations, where the diagnosis of psoriasis was concluded and confirmed by skin biopsies. The patients were successfully treated with anti-psoriasis topical and/or systemic medications. Psoriasis Vaccinalis has been previously described with several vaccines. COVID-19 vaccines are not an exception, and new-onset pustular psoriasis can occur after any type of COVID-19 vaccination, thereby mimicking a skin infection in its early stage. Primary care clinicians should remain vigilant for potential cases of vaccine-induced psoriasis to prevent misdiagnosis and facilitate a timely referral to dermatology.
