ImmunoTargets and Therapy最新文献

{"title":"VISTA Confers Renal Protection in Murine Hemorrhage/Infection-Induced Acute Kidney Injury: Associations with Altered NGAL and HMGB1 Expression.","authors":"Yuan Yuan, Lei Fang, Yangliang Yang, Mengzhi Pan, Daoqin Gao, Chuan Geng, Baoji Hu","doi":"10.2147/ITT.S641577","DOIUrl":"https://doi.org/10.2147/ITT.S641577","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) represents a serious complication associated with both short- and long-term morbidity and mortality in critically ill patients. Severe trauma complicated by infection represents a high‑risk clinical trigger for AKI. V‑domain immunoglobulin suppressor of T‑cell activation (VISTA) is an immune‑checkpoint molecule with immunomodulatory functions, yet its role in trauma‑sepsis‑induced AKI remains incompletely defined.</p><p><strong>Methods: </strong>In this experimental study, male wild‑type (WT) and VISTA‑deficient (VISTA^-/-) C57BL/6 mice were utilized to establish a two‑hit murine AKI model combining hemorrhagic shock and cecal ligation and puncture (Hem/CLP). Blood and kidney tissues were collected 24 hours after hemorrhage/CLP. VISTA expression on neutrophils and monocytes in peripheral blood was assessed by flow cytometry. Serum creatinine and blood urea nitrogen were measured according to manufacturer protocols. Cytokine levels were determined by ELISA, and corresponding mRNA expression was analyzed via RT-PCR. Kidney injury severity was evaluated histologically by pathologists. Protein levels of neutrophil gelatinase-associated lipocalin and high mobility group box 1 were examined by Western blot.</p><p><strong>Results: </strong>VISTA expression was significantly elevated on circulating neutrophils and monocytes following injury (all <i>p</i> < 0.05). Histopathological assessment revealed aggravated kidney injury in the AKI model (<i>p =</i> 0.0056), which was further exacerbated in VISTA-deficient mice (<i>p =</i> 0.0357). Consistent with this, serum creatinine (<i>p =</i> 0.014) and blood urea nitrogen (<i>p =</i> 0.005) levels were markedly higher in VISTA-deficient mice compared to controls. Pro-inflammatory cytokines IL-6 (<i>p =</i> 0.0335) and TNF-α (<i>p =</i> 0.0283) were increased in AKI mice and further elevated in VISTA-deficient mice (<i>p =</i> 0.0014 and 0.0001, respectively), whereas anti-inflammatory IL-10 showed a converse trend (<i>p =</i> 0.0056 and 0.0019, respectively). RT-PCR confirmed corresponding changes in cytokine mRNA expression. Western blot analysis indicated decreased neutrophil gelatinase-associated lipocalin (<i>p <</i> 0.0001) and increased high mobility group box 1 protein (<i>p =</i> 0.0009) levels in VISTA-deficient mice.</p><p><strong>Conclusion: </strong>Collectively, our results demonstrate that VISTA‑deficient mice develop more severe early‑phase hemorrhage/sepsis‑induced AKI. Altered NGAL and HMGB1 protein expression occur in parallel with VISTA‑associated renal protection; further functional validation is required to establish causal mechanistic relationships and to evaluate the translational potential of VISTA‑targeted approaches.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"641577"},"PeriodicalIF":4.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential Benefits of Biologic Therapies Beyond Respiratory Allergy.","authors":"Rossella Sica, Francesco Catamerò, Simone Foti Randazzese, Francesca Galletta, Amelia Licari, Gian Luigi Marseglia, Francesca Mori, Remo Poto, Federica Pulvirenti, Silvia Ricci, Mattia Giovannini, Sara Manti","doi":"10.2147/ITT.S624173","DOIUrl":"https://doi.org/10.2147/ITT.S624173","url":null,"abstract":"<p><p>Severe pediatric asthma is a heterogeneous inflammatory disease that is most commonly driven by type 2 (T2) inflammation. Because respiratory viral infections are the leading triggers of asthma exacerbations in children, this review examines the effects of biologic therapies on infection-related outcomes and antiviral immune function, beyond their established role in asthma control. We conducted a structured narrative review of literature published from January 2000 through February 2026 using PubMed/MEDLINE, EMBASE, Scopus, and the Cochrane Library databases. Studies evaluating infection-related outcomes and immune effects of biologic therapies in pediatric asthma were analyzed. Available evidence consistently indicates that biologics have favorable infectious safety profiles without increasing the risk of serious or opportunistic infections. Anti-IgE therapy (omalizumab) showed the strongest evidence of direct immunomodulatory effects, including restoration of interferon-mediated antiviral responses and reduction of virus-triggered asthma exacerbations. Anti-IL-5 and anti-IL-5 receptor therapies have corticosteroid-sparing effects and preserve immune competence despite eosinophil depletion. Dupilumab and tezepelumab similarly provide sustained efficacy and stable safety profiles without increasing infectious burden. Real-world evidence from the COVID-19 pandemic further indicates that biologic-treated children do not have greater susceptibility to SARS-CoV-2 infection or more severe disease. Overall, biologic therapies appear to provide targeted immunomodulation rather than broad immunosuppression, preserving host defense while controlling severe pediatric asthma. These findings suggest that biologic therapies may positively influence immune competence beyond asthma control, with implications for infection susceptibility and antiviral defense. Further prospective pediatric studies with standardized endpoints and long-term follow-up are needed to define their immunological impact and optimize precision-medicine strategies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"624173"},"PeriodicalIF":4.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Multifaceted Roles of STAT6: Implications for Precision Immunotherapeutics.","authors":"Hiba Narvel, Daisuke Nishizaki, Shumei Kato, Razelle Kurzrock","doi":"10.2147/ITT.S585744","DOIUrl":"10.2147/ITT.S585744","url":null,"abstract":"<p><p>STAT6, located on chromosome 12, encodes a transcription factor whose SH2 domain is central to its activation. While classically a Th2 mediator, aberrant STAT6 activation is observed in diverse malignancies. This review focuses on the molecular and functional landscape of STAT6, primarily in cancer and tumor immunology, while also surveying its emerging roles in allergy, infection, and autoimmunity to illustrate context-dependent signaling and identify areas for future investigation. In tumors, STAT6 fosters immunosuppression by polarizing macrophages toward M2 phenotypes and upregulates checkpoint ligands, while promoting oncogenic phenotypes (survival, angiogenesis, metastasis) through crosstalk with STAT3, NF-κB, and others. STAT6 can be activated both canonically (IL-4/IL-13 via JAKs) and noncanonically (eg, STING signaling). Somatic hotspot mutations (notably D419) enhance DNA binding and nuclear retention, and germline polymorphisms to gain-of-function alleles span a continuum of allergic phenotypes. In infection, STAT6 is essential for helminth clearance but may antagonize protective Th1 responses against viruses and bacteria. In autoimmunity, its role is context-dependent: pathogenic in some settings, regulatory in others. STAT6 emerges as a context-specific \"switch node\" in immunity and cancer. Its multifaceted contributions highlight the need for further research to determine whether therapeutic targeting-and if so, which biomarker-guided, context-dependent strategies-might be feasible in selected disease settings.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"585744"},"PeriodicalIF":4.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Single-Cell-Derived CD8+ T-Cell State Plasticity Score for Prognostic Stratification and Characterization of Immune Responsiveness in Hepatocellular Carcinoma.","authors":"Le Xing, Dan He, Dong-Mei Li, Zhong Liang, Chen Yue, Cheng-Yang Zhang, Ying-Chen Hou, Chen-Yu Jiang, Guang-Ding Zhou, Hongjiao Yu, Yan-Ling Zhang, Yan-Xia Shi, Lin-Hai Li, Ming Liu","doi":"10.2147/ITT.S626002","DOIUrl":"10.2147/ITT.S626002","url":null,"abstract":"<p><strong>Background: </strong>T cells play a central role in antitumor immunity. Emerging evidence indicates that T-cell plasticity and differentiation states are associated with clinical outcomes and responses to cancer immunotherapy. CD8⁺ T cells that retain differentiation potential are thought to sustain effective antitumor immunity. However, robust quantitative metrics for assessing tumor-infiltrating CD8⁺ T-cell state plasticity and defining its clinical significance in hepatocellular carcinoma remain lacking.</p><p><strong>Methods: </strong>We integrated publicly available single-cell RNA-sequencing datasets from HCC cohorts to characterize CD8⁺ T-cell states using unsupervised pseudotime reconstruction and supervised ordinal transcriptional modeling. We used genes showing progressive changes along the inferred state axis and enriched in CD8⁺ T cells to develop a T-cell State Plasticity score using Cox proportional hazards and LASSO regression in the training cohort. The model was evaluated in independent bulk transcriptomic cohorts.</p><p><strong>Results: </strong>Supervised psupertime analysis validated the predefined Tcm-Tem-Tpex-Ttex ordinal axis in held-out cells, supporting the existence of an ordered CD8⁺ T-cell state continuum in HCC. The CD8⁺ T-cell State Plasticity score robustly stratified clinical outcomes across multiple large HCC cohorts. High-risk scores, indicative of reduced CD8⁺ T-cell state plasticity, were associated with adverse clinical outcomes and an immunosuppressive tumor immune microenvironment.</p><p><strong>Conclusion: </strong>CD8+ T-cell states are associated with tumor immune characteristics and clinical outcomes in HCC. This single-cell-derived T cell plasticity scoring system provides a quantitative framework for prognostic prediction and immune landscape evaluation, with potential implications for clinical decision-making.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"626002"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Nonspecific Autoantibodies with Recurrent Pregnancy Loss and Pregnancy Outcomes Following Immunological Intervention: A Single-Centre Retrospective Cohort Study.","authors":"Xinying Xie, Yalan Mo, Ma Huang, Pengzhong Hou","doi":"10.2147/ITT.S630100","DOIUrl":"10.2147/ITT.S630100","url":null,"abstract":"<p><strong>Background: </strong>Immune dysfunction has been implicated in the aetiology of recurrent pregnancy loss (RPL). While there are currently clear guidelines for the diagnosis and treatment of connective tissue diseases and typical/atypical antiphospholipid syndrome, with highly effective outcomes, none exist for patients with RPL who, despite a lack of clinical symptoms, have abnormal levels of two or more immune-related markers. This study aimed to evaluate the relationship between non-specific autoantibodies and RPL, as well as the impact of immunotherapy on pregnancy outcomes in patients with RPL and positive antinuclear antibody (ANA) profiles.</p><p><strong>Methods: </strong>A comparison was made between the prevalence of ANAs in patients with recurrent spontaneous abortion (RPL) and that in women with normal pregnancies. Additionally, the pregnancy outcomes of 102 pregnant women-who were found to be positive for a profile of two or more ANAs during follow-up at our hospital's rheumatology and immunology outpatient clinic and reproductive medicine department-were assessed following early immunomodulatory treatment [hydroxychloroquine (HCQ, 0.2 g per dose, twice daily) + glucocorticoids (prednisone 5-10 mg/day) + aspirin 0.1 g/day]. We then compared these outcomes with those of ANA-positive pregnant women attending the Reproductive Medicine Department who did not receive immunotherapy.</p><p><strong>Results: </strong>In the observation group of 102 cases, 76 women gave birth successfully following early immunological intervention, with a normal pregnancy rate of 76/87 (87.4%). In the control group of 90 cases, the normal pregnancy rate was 27/64 (42.2%). A comparison of the sustained pregnancy rates between the two groups revealed a statistically significant difference (χ² = 34.69, P < 0.001). A higher proportion of women with abnormal ANA levels were observed in the group with normal pregnancies. Among women with recurrent pregnancy loss (RPL) and abnormal ANA levels, the higher the ANA positivity rate, the higher the miscarriage rate; women with RPL and abnormal ANA levels achieved a significantly higher pregnancy success rate following immunotherapy than those who did not receive immunotherapy.</p><p><strong>Conclusion: </strong>In patients with recurrent pregnancy loss who exhibit autoimmune features, higher ANA titres, a greater number of positive ANA specificities, elevated IgG levels, and decreased complement levels are each independently associated with an increased likelihood of recurrent miscarriage. Importantly, early immunomodulatory intervention appears to mitigate these adverse pregnancy outcomes.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"630100"},"PeriodicalIF":4.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACBP/DBI Neutralization Stimulates Anticancer Immune Responses by Upregulating Lamin A in T Cells.","authors":"Sijing Li, Carlos López-Otín, Maria Chiara Maiuri, Isabelle Martins, Guido Kroemer","doi":"10.2147/ITT.S604318","DOIUrl":"10.2147/ITT.S604318","url":null,"abstract":"<p><strong>Introduction: </strong>Acyl CoA binding protein (ACBP, encoded by the gene <i>diazepam binding inhibitor</i>, DBI) is a tissue stress hormone involved in pathological aging that mediates immunosuppression. The antibody-mediated neutralization of ACBP/DBI enhances anticancer immune responses in the context of chemoimmunotherapy. ACBP/DBI inhibition also upregulates the expression of the anti-aging gene <i>Lmna</i> coding for Lamin A in tumor-infiltrating T lymphocytes. This study was designed to explore the role of <i>Lmna</i> in the anticancer effects of ACBP/DBI neutralization.</p><p><strong>Methods: </strong>We generated mice lacking <i>Lmna</i> expression in T lymphocytes due to a conditional knockout. Mice bearing orthotopic (cutaneous) MCA205 fibrosarcomas were treated with an anti-ACBP/DBI monoclonal antibody in the context of chemoimmuntherapy (oxaliplatin combined with a PD-1 blocking antibody), and tumor growth was monitored.</p><p><strong>Results: </strong>As compared to immunocompetent control mice, in which ACBP/DBI neutralization plus chemoimmunotherapy was highly efficient in reducing MCA205 growth, mice lacking ACBP/DBI in T cells largely failed to respond to the therapeutic intervention. This result was undistinguishably observed in both female and male mice.</p><p><strong>Discussion: </strong>Altogether, these results indicate that <i>Lmna</i> expression by T lymphocytes is required for the anticancer effects of the combination of chemoimmunotherapy and ACBP/DBI neutralization. We conclude that lamin A, a factor required for optimal T cell activation, is causally involved in the immunostimulatory effects of ACBP/DBI neutralization.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"604318"},"PeriodicalIF":4.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Myeloid-Specific Endogenous TRP1-CAR Knock-in Mouse Model for Melanoma-Targeted Immunotherapy.","authors":"Yuxin Hao, Xin Chen, Min Wang, Jinxiang Han, Jihong Pan, Luo Zhang, Xiushan Yin","doi":"10.2147/ITT.S628775","DOIUrl":"10.2147/ITT.S628775","url":null,"abstract":"<p><strong>Background: </strong>Malignant melanoma is highly aggressive and prone to therapeutic resistance. Chimeric antigen receptor macrophage (CAR-M) therapy is promising for solid tumors, but conventional ex vivo-engineered CAR-M has limited in vivo persistence, complicating longer-term safety evaluation. This study established a myeloid-specific, endogenously expressed tyrosinase-related protein 1 (TRP1)-CAR mouse model to assess antitumor activity and safety.</p><p><strong>Methods: </strong>TRP1-CAR was conditionally knocked into the Rosa26 locus and crossed with Lysozyme 2 <i>(Lyz2)</i>-Cre mice to generate mice with myeloid-specific TRP1-CAR expression (TRP1-CAR^M). CAR signals and baseline observations were assessed by flow cytometry, tissue immunofluorescence, histopathology, and hematology. Phagocytosis, cytotoxicity, and inflammation-related gene expression were evaluated in vitro. A syngeneic B16-Fluc-GFP melanoma model was used in two independent cohorts to assess tumor growth, survival, intratumoral CD8⁺ T-cell infiltration, and histopathology.</p><p><strong>Results: </strong>CAR signals were detected in peripheral blood and in F4/80-positive macrophage-containing areas of the lung, liver, and spleen. No overt histopathological abnormalities or hematological changes were observed in the tissues examined under baseline conditions. TRP1-CAR^M-BMDMs showed enhanced phagocytic and cytotoxic activity against B16-Fluc-GFP cells, accompanied by altered inflammation-related gene expression in the co-culture system. In vivo, TRP1-CAR^M mice showed delayed tumor growth (P < 0.0001) and prolonged survival (P = 0.0005), with increased intratumoral CD8⁺ T-cell infiltration.</p><p><strong>Conclusion: </strong>This myeloid-specific TRP1-CAR knock-in model showed in vitro antitumor activity and delayed melanoma progression in vivo. It provides a proof-of-concept framework for investigating antitumor activity and preliminary safety observations associated with sustained endogenous CAR expression.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"628775"},"PeriodicalIF":4.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newcastle Disease Virus - Induced Interferons Regulate PD-L1 and MICA Expression in Human Tumor and Normal Cells.","authors":"Teridah Ernala Ginting, Young Othiwi Larasati, Vina Cornelia, Nur Rahmaniah Hidayat, Salomo Christian, Kamaluddin Zarkasie, Irawan Yusuf","doi":"10.2147/ITT.S614889","DOIUrl":"10.2147/ITT.S614889","url":null,"abstract":"<p><strong>Purpose: </strong>To explore whether NDV and/or NDV-induced IFNs regulate programmed death-1 ligand (PD-L1) expression and modulate the balance between inhibitory and stimulatory immune signals.</p><p><strong>Materials and methods: </strong>Human non-malignant (NB1RGB and HEK293) and tumor (A549 and U87MG) cell lines were used. Cells were either infected with Newcastle disease virus (NDV) LaSota strain or treated with interferons (IFNs). PD-L1 expression was analyzed by flow cytometry, Western blotting, and immunofluorescence. The relationship between PD-L1, as an immune inhibitor, and major histocompatibility complex class I polypeptide-related sequence A (MICA), as an immune activator, was evaluated using duplex chromogenic in situ hybridization. To investigate whether the NDV-induced shift in the PD-L1/MICA axis was sufficient to activate natural killer group 2 member D (NKG2D) receptor-possessing cells within peripheral blood mononuclear cells (PBMCs), IFN-γ production was measured in PBMCs following 24 hours of co-culture with tumor and normal cell lines previously infected with NDV or treated with IFN-λ.</p><p><strong>Results: </strong>NDV infection and IFN treatment resulted in a reduction of PD-L1 expressions in specific cell types. This decrease was accompanied by a concurrent increase in MICA expression, as demonstrated by in situ hybridization. The shift in balance between PD-L1 and MICA correlated with enhanced activation of NKG2D receptor-expressing immune cells, evidenced by increased IFN-γ secretion.</p><p><strong>Conclusion: </strong>These findings suggest that NDV may exert antitumor effects by modulating the balance between inhibitory checkpoint molecules and stimulatory ligands, specifically through downregulation of PD-L1 and upregulation of MICA. This mechanism highlights the potential of NDV to enhance cytotoxic immune responses and supports its further development as a novel strategy in cancer immunotherapy.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"614889"},"PeriodicalIF":4.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Clinical and Prognostic Features of Acute and Chronic Active Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis in Adults: A Scoping Review.","authors":"Tiankuo Gao, Chun Yang, Yingxin Zhu, Junling Hu, Chen Gong, Yini Wang, Yue Song","doi":"10.2147/ITT.S621828","DOIUrl":"10.2147/ITT.S621828","url":null,"abstract":"<p><p>Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a major subtype of secondary HLH and is increasingly recognized as a heterogeneous entity. However, the clinical differences between acute EBV-HLH (AEBV-HLH) and chronic active EBV infection-associated HLH (CAEBV-HLH) have not been systematically characterized. We conducted a scoping review of PubMed up to December 7, 2024, and identified 168 eligible articles involving 714 adult patients with EBV-HLH, including 584 with AEBV-HLH and 130 with CAEBV-HLH. Epidemiologic features, clinical manifestations, treatment patterns, and prognostic factors were summarized and compared between the two subgroups. Patients with AEBV-HLH showed more severe HLH-related abnormalities, including lower blood counts and higher ferritin, triglyceride, lactate dehydrogenase, and plasma EBV-DNA levels, whereas central nervous system involvement was more frequent in CAEBV-HLH. The median overall survival was significantly longer in CAEBV-HLH (8.9 months) than AEBV-HLH (2.4 months, P=0.005). In the overall cohort, ferritin >5000 μg/L, soluble CD25 >10000 U/mL, EBV-DNA >10000 copies/mL, and receiving hematopoietic stem cell transplantation (HSCT) were independently associated with better overall survival. In subgroup analyses, soluble CD25, EBV-DNA, and HSCT remained independent predictors in AEBV-HLH, whereas undergoing HSCT was the only independent prognostic factor in CAEBV-HLH. These findings support distinct clinical and prognostic characteristics between AEBV-HLH and CAEBV-HLH, especially in adults. AEBV-HLH is characterized by a more fulminant inflammatory presentation, whereas CAEBV-HLH more often follows a chronic course with greater extensive organ. HSCT appears to be central to long-term outcome in both subtypes.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"621828"},"PeriodicalIF":4.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal B Cell Receptor Repertoire Profiling of Heavy- and Light-Chain Features in Injured Rat Spinal Cord Tissue After Traumatic Spinal Cord Injury.","authors":"Taotao Lin, Chao Qin, Ruixiong Du, Qijian Lu, Zhiyi Wang, Rongcan Wu, Hailin Lin, Xianfeng Lin, Gang Chen, Wenge Liu, Zhenyu Wang","doi":"10.2147/ITT.S627135","DOIUrl":"10.2147/ITT.S627135","url":null,"abstract":"<p><strong>Purpose: </strong>B cell receptor (BCR) repertoire features detectable in injured spinal cord tissue after traumatic spinal cord injury (SCI) remain poorly characterized. This study performed an exploratory longitudinal analysis of immunoglobulin heavy-chain (IGH) and light-chain (IGL) repertoire features in injured rat spinal cord tissue.</p><p><strong>Methods: </strong>Adult male Sprague-Dawley rats underwent traumatic SCI using a modified Allen's weight-drop model. Lesion-centered spinal cord tissues were collected at 1, 3, 7, 14, and 28 days post-injury, with four biological replicates per time point. BCR repertoire sequencing was used to assess functional sequence composition, isotype or constant-region distribution, sequencing saturation, diversity indices, germline-divergence metrics, V/J gene usage, V-J pairing, CDR3 length distribution, dominant clonotype abundance, and repertoire similarity. Uninjured baseline libraries failed construction; therefore, analyses were restricted to post-injury samples and interpreted descriptively.</p><p><strong>Results: </strong>Productive BCR sequences were detected across injured spinal cord samples, and saturation curves supported repertoire coverage in most samples. IGH repertoires showed greater inter-sample heterogeneity in isotype composition, diversity indices, germline-divergence metrics, V/J gene usage, V-J pairing, CDR3 length distribution, dominant clonotype abundance, and clonotype sharing. In contrast, IGL repertoires were predominantly IgK-associated and showed a restricted CDR3 length distribution centered at 11 amino acids, with higher repertoire sharing. These heavy- and light-chain contrasts are best interpreted as repertoire-architecture differences within the post-injury dataset.</p><p><strong>Conclusion: </strong>Injured male rat spinal cord tissue contained detectable BCR repertoire signals with descriptive variation across post-injury time points, supporting the feasibility of longitudinal repertoire profiling in this setting. These data provide a receptor-level resource for SCI neuroimmunology and support future studies to clarify antigen specificity, functional relevance, and translational potential of post-injury B-cell responses.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"627135"},"PeriodicalIF":4.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}