Pub Date : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.clim.2025.110660
Jun Han , Qifeng Yao , Qiuyue Huang , Zuoyou Ding , Guohao Wu
Cancer cachexia involves severe skeletal muscle and adipose tissue loss. The role of Apolipoprotein E (ApoE) in adipose remodeling remains unclear. This study investigated ApoE's function in cancer cachexia. We found cachectic patients had decreased plasma ApoE but elevated expression in subcutaneous adipose. In vitro, ApoE knockdown in adipocytes downregulated both lipogenesis and lipolysis genes. In vivo, ApoE−/− mice were protected against adipose wasting in a cachexia model. Single-cell RNA sequencing revealed ApoE deficiency altered immune cell dynamics, increasing total macrophages and enriching a specific Cbr2+ macrophage subpopulation with an M2-like phenotype. This was confirmed by immunofluorescence showing enhanced M2 macrophage infiltration in adipose tissue. We conclude that ApoE is a critical regulator of adipose homeostasis and immune modulation in cancer cachexia, representing a promising diagnostic and therapeutic target.
{"title":"Single-cell sequencing reveals APOE deletion alleviates adipose wasting in cancer cachexia via macrophage repolarization","authors":"Jun Han , Qifeng Yao , Qiuyue Huang , Zuoyou Ding , Guohao Wu","doi":"10.1016/j.clim.2025.110660","DOIUrl":"10.1016/j.clim.2025.110660","url":null,"abstract":"<div><div>Cancer cachexia involves severe skeletal muscle and adipose tissue loss. The role of Apolipoprotein E (ApoE) in adipose remodeling remains unclear. This study investigated ApoE's function in cancer cachexia. We found cachectic patients had decreased plasma ApoE but elevated expression in subcutaneous adipose. In vitro, ApoE knockdown in adipocytes downregulated both lipogenesis and lipolysis genes. In vivo, ApoE<sup>−/−</sup> mice were protected against adipose wasting in a cachexia model. Single-cell RNA sequencing revealed ApoE deficiency altered immune cell dynamics, increasing total macrophages and enriching a specific Cbr2+ macrophage subpopulation with an M2-like phenotype. This was confirmed by immunofluorescence showing enhanced M2 macrophage infiltration in adipose tissue. We conclude that ApoE is a critical regulator of adipose homeostasis and immune modulation in cancer cachexia, representing a promising diagnostic and therapeutic target.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110660"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-25DOI: 10.1016/j.clim.2025.110661
Wei Qiu , Ya Huang , Yan Gu , Yichi Sun , Ping Yue , KaiDe Xia , Shichao Zhang
Emerging data have revealed that m1A modification and its regulators are key participants in tumorigenesis and progression. The cell-free miRNAs have been demonstrated to circulate stably in the serum, making them biomarker candidates for cancer diagnosis. Here we included 16,902 serum samples to develop a diagnostic signature named m1A-miRNA signature based on serum circulating m1A-related miRNAs for cancer detection. The m1A-miRNA signature presented excellent accuracy, and the area under the curve (AUC) was 0.991 in the training cohort. The diagnostic capability of the m1A-miRNA signature was not affected by sexual distinction, age and non-cancer disease. As far as distinguishing cancer types is concerned, the signature exerted superior ability in identifying the types of glioblastoma multiforme, gastric cancer and lung cancer. We also found that the m1A-miRNA signature showed a satisfactory AUC in the early diagnosis of pan-cancer. Additionally, the accuracy of the m1A-miRNA signature was further verified by clinical samples.
{"title":"A novel diagnostic signature constructed based on serum-circulating m1A-related miRNAs for cancer detection","authors":"Wei Qiu , Ya Huang , Yan Gu , Yichi Sun , Ping Yue , KaiDe Xia , Shichao Zhang","doi":"10.1016/j.clim.2025.110661","DOIUrl":"10.1016/j.clim.2025.110661","url":null,"abstract":"<div><div>Emerging data have revealed that m<sup>1</sup>A modification and its regulators are key participants in tumorigenesis and progression. The cell-free miRNAs have been demonstrated to circulate stably in the serum, making them biomarker candidates for cancer diagnosis. Here we included 16,902 serum samples to develop a diagnostic signature named m1A-miRNA signature based on serum circulating m<sup>1</sup>A-related miRNAs for cancer detection. The m1A-miRNA signature presented excellent accuracy, and the area under the curve (AUC) was 0.991 in the training cohort. The diagnostic capability of the m1A-miRNA signature was not affected by sexual distinction, age and non-cancer disease. As far as distinguishing cancer types is concerned, the signature exerted superior ability in identifying the types of glioblastoma multiforme, gastric cancer and lung cancer. We also found that the m1A-miRNA signature showed a satisfactory AUC in the early diagnosis of pan-cancer. Additionally, the accuracy of the m1A-miRNA signature was further verified by clinical samples.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110661"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-13DOI: 10.1016/j.clim.2025.110656
Chrysanthi Sidiropoulou , Garyphallia Poulakou , Evdoxia Kyriazopoulou , Elisavet Tasouli , Efthymia Giannitsioti , Anna Strikou , Maria Tsilika , Eirini Christaki , Vassiliki Rapti , Vassiliki Evangelopoulou , Nikoletta Rovina , Nathalie Iannotti , Emanuele Nicastri , Eleonora Taddei , Helena Florou , Andrea Angheben , Matteo Bassetti , Lorenzo Dagna , Antonio Torres , Spyros Foutadakis , Evangelos J. Giamarellos-Bourboulis
Post-Acute COVID-19 syndrome (PACS) is heterogeneous in phenotype and functional state. This prospective, observational study studied adults six months after acute COVID-19. We defined clinical phenotypes and profiled plasma mediators grouped into functional pathways (IL-1, IL-17, IFNγ/IFNγ-related cytokines, pro−/anti-inflammatory clusters). A subset underwent RNA-seq and ChIP-seq experiments. Three cohorts were analyzed (Exploratory n = 46; Discovery n = 591; Validation Cohort n = 289). PACS compatible symptoms were identified in 69.6 %; 59.2 % and 54.7 % respectively. Five phenotypes emerged. IL-1 cytokines (OR: 3.17, 95 % CIs: 1.94–5.19, p: 4.5 × 10−6), IL-17 cytokines (OR: 2.45, 95 % CIs: 1.47–4.07 p: 5.88 × 10−4) and the anti-inflammatory biomarkers (OR: 2.15, 95 % CIs: 1.34–3.45, p: 1.5 × 10−3) were upregulated in PACS patients. Respiratory phenotype was correlated with IL-1 upregulation (OR 4.23; 95 % CIs, 1.69–10.8, p = 0.0025). Transcriptomic and epigenomic changes were observed. Distinct phenotypes of PACS are driven by different immunological mechanisms at the DNA, transcriptomic, and protein levels.
Pub Date : 2026-02-01Epub Date: 2025-12-21DOI: 10.1016/j.clim.2025.110659
Temesgen E. Andargie , Han Su , Moon Kyoo Jang , Xin Tian , Andrew H. Karaba , Sean Agbor-Enoh
The association between circulating cytokines and allograft injury due to allograft rejection (AR) remains poorly defined. We hypothesize that cytokines correlate with the degree of allograft injury during AR. This case-control study measured cytokines and cell-free DNA in 88 heart transplant plasma samples (54 AR, 34 non-rejecting (NR) controls) and 26 healthy controls. AR patients exhibited higher levels of total and percent donor-derived cfDNA (%dd-cfDNA) and proinflammatory cytokines, and lower levels of type II cytokines/chemokines and Th17/23 axis cytokines compared to NR or HCs. The cfDNA levels positively correlated with proinflammatory cytokines and negatively with MDC and cytokines of the Th17/IL-23 axis. A Lasso regression model combining cytokines and %dd-cfDNA (AUC = 0.93) showed better AR diagnostic performance than either cytokines or %dd-cfDNA alone. The study concluded that inflammatory and regulatory cytokine levels correlate with allograft injury, and combining cytokines with %dd-cfDNA may enhance AR detection.
{"title":"Systemic cytokine profiling enhances the performance of dd-cfDNA to detect cardiac rejection","authors":"Temesgen E. Andargie , Han Su , Moon Kyoo Jang , Xin Tian , Andrew H. Karaba , Sean Agbor-Enoh","doi":"10.1016/j.clim.2025.110659","DOIUrl":"10.1016/j.clim.2025.110659","url":null,"abstract":"<div><div>The association between circulating cytokines and allograft injury due to allograft rejection (AR) remains poorly defined. We hypothesize that cytokines correlate with the degree of allograft injury during AR. This case-control study measured cytokines and cell-free DNA in 88 heart transplant plasma samples (54 AR, 34 non-rejecting (NR) controls) and 26 healthy controls. AR patients exhibited higher levels of total and percent donor-derived cfDNA (%dd-cfDNA) and proinflammatory cytokines, and lower levels of type II cytokines/chemokines and Th17/23 axis cytokines compared to NR or HCs. The cfDNA levels positively correlated with proinflammatory cytokines and negatively with MDC and cytokines of the Th17/IL-23 axis. A Lasso regression model combining cytokines and %dd-cfDNA (AUC = 0.93) showed better AR diagnostic performance than either cytokines or %dd-cfDNA alone. The study concluded that inflammatory and regulatory cytokine levels correlate with allograft injury, and combining cytokines with %dd-cfDNA may enhance AR detection.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110659"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human endogenous retrovirus W (HERV-W) has been linked to multiple sclerosis (MS), yet its pathogenic role remains unclear. Epstein–Barr virus (EBV), a key MS risk factor, can transactivate HERVs, suggesting a potential interplay. We analyzed immune responses to a HERV-W₁₀₃–₁₁₀ peptide homologous to EBV EBNA1₃₈₆–₄₀₅ in sera from Japanese MS patients (n = 44), neurological controls (n = 28), and healthy controls (n = 48), including an unrelated control antigen (BCG) to assess general humoral activation. MS patients exhibited elevated antibodies to both peptides, indicating cross-reactive immunity. In C57BL/6 J mice, pre-immunization with either peptide modestly modulated experimental autoimmune encephalomyelitis (EAE), whereas combined pre-immunization exacerbated disease, expanding CD4+ and CD8+ T cells and promoting systemic activation. These results support a model in which EBV-driven HERV-W activation elicits cross-reactive humoral and cellular responses that amplify neuroinflammation in MS.
{"title":"Cross-reactive HERV-W and EBV peptides elicit antibody responses in MS patients and synergistically exacerbate neuroinflammation in EAE","authors":"Davide Cossu , Yuji Tomizawa , Tamami Sakanishi , Stefano Ruberto , Taku Hatano , Nobutaka Hattori","doi":"10.1016/j.clim.2025.110644","DOIUrl":"10.1016/j.clim.2025.110644","url":null,"abstract":"<div><div><em>Human endogenous retrovirus W</em> (HERV-W) has been linked to multiple sclerosis (MS), yet its pathogenic role remains unclear. <em>Epstein–Barr virus</em> (EBV), a key MS risk factor, can transactivate HERVs, suggesting a potential interplay. We analyzed immune responses to a HERV-W₁₀₃–₁₁₀ peptide homologous to EBV EBNA1₃₈₆–₄₀₅ in sera from Japanese MS patients (<em>n</em> = 44), neurological controls (<em>n</em> = 28), and healthy controls (<em>n</em> = 48), including an unrelated control antigen (BCG) to assess general humoral activation. MS patients exhibited elevated antibodies to both peptides, indicating cross-reactive immunity. In C57BL/6 J mice, pre-immunization with either peptide modestly modulated experimental autoimmune encephalomyelitis (EAE), whereas combined pre-immunization exacerbated disease, expanding CD4<sup>+</sup> and CD8<sup>+</sup> T cells and promoting systemic activation. These results support a model in which EBV-driven HERV-W activation elicits cross-reactive humoral and cellular responses that amplify neuroinflammation in MS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110644"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-16DOI: 10.1016/j.clim.2025.110657
Hui Wu , Xianglin Chu , Huahua Zhong , Ying Huang , Hongxia Yang , Guoyan Qi , Lei Jin , Ran Chen , Wenji Jia , Ji Xiong , Liewen Pang , Chongbo Zhao , Jie Song , Sushan Luo
The efficacy of eculizumab as a perioperative treatment in patients with thymoma-associated myasthenia gravis (TAMG) has not been evaluated. This prospective study included patients with TAMG who received standard-of-care therapy (Soc group, n = 20) or combined with eculizumab (Ecu group, n = 13). At 1 week, the Ecu group showed a marked improvement compared to the Soc group, as evidenced by a reduction in Quantitative Myasthenia Gravis (QMG) (7.39 ± 3.47 vs 0.25 ± 5.13, P= 0.0001), Manual Muscle Test (MMT) (6.39 ± 4.66 vs 0.15 ± 3.96, P = 0.0003), and MG Activities of Daily Living (MG-ADL) (4.85 ± 3.16 vs 0.30 ± 3.47, P = 0.0006). No significant differences were observed in operative time, or intraoperative blood loss. The rate of postoperative myasthenic crisis was 9.1 % (1/13) in the Ecu group, compared to 20 % (4/20) in the Soc group (P = 0.33). This study highlights the role of eculizumab in TAMG as a rapid symptom-control treatment before thymomectomy.
{"title":"Eculizumab as a new option for perioperative treatment in thymoma-associated myasthenia gravis","authors":"Hui Wu , Xianglin Chu , Huahua Zhong , Ying Huang , Hongxia Yang , Guoyan Qi , Lei Jin , Ran Chen , Wenji Jia , Ji Xiong , Liewen Pang , Chongbo Zhao , Jie Song , Sushan Luo","doi":"10.1016/j.clim.2025.110657","DOIUrl":"10.1016/j.clim.2025.110657","url":null,"abstract":"<div><div>The efficacy of eculizumab as a perioperative treatment in patients with thymoma-associated myasthenia gravis (TAMG) has not been evaluated. This prospective study included patients with TAMG who received standard-of-care therapy (Soc group, <em>n</em> = 20) or combined with eculizumab (Ecu group, <em>n</em> = 13). At 1 week, the Ecu group showed a marked improvement compared to the Soc group, as evidenced by a reduction in Quantitative Myasthenia Gravis (QMG) (7.39 ± 3.47 vs 0.25 ± 5.13, <em>P</em> <em>=</em> 0.0001), Manual Muscle Test (MMT) (6.39 ± 4.66 vs 0.15 ± 3.96, <em>P</em> = 0.0003), and MG Activities of Daily Living (MG-ADL) (4.85 ± 3.16 vs 0.30 ± 3.47, <em>P</em> = 0.0006). No significant differences were observed in operative time, or intraoperative blood loss. The rate of postoperative myasthenic crisis was 9.1 % (1/13) in the Ecu group, compared to 20 % (4/20) in the Soc group (<em>P</em> = 0.33). This study highlights the role of eculizumab in TAMG as a rapid symptom-control treatment before thymomectomy.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110657"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.clim.2025.110655
Qianwen Tian , Qi Xi , Qiaolin Zhang , Yun Chen , Yunxin Zhang , Fuxue Kuang , Lejie Sun , Song Peng , Huaxun Wu
Primary Sjögren disease (pSS) is an autoimmune disease characterized primarily by predominant lymphocytic infiltration of the exocrine glands. While the etiopathogenesis of pSS remains unclear, current therapeutic strategies lack efficacy. In human submandibular gland epithelial cells (HSGECs), endoplasmic reticulum stress (ERS) induces apoptosis, leading to the cellular redistribution of Ro52/SSA autoantigens, the activation of the immune system, and the production of a large number of autoantibodies. Cells initiate autophagy to resist cellular damage caused by ERS and restore the normal physiological status. The ERK1/2-mTOR-autophagy signaling pathway has been implicated in numerous pathological conditions. In this study, an experimental Sjögren disease (ESS) mouse model was established to evaluate reduced protein levels and altered intracellular distribution of Ro52/SSA autoantigens through modulation of ERS and the ERK1/2-mTOR-autophagy pathway, resulting in diminished autoantibody production and ameliorated ESS symptoms. These findings provide an experimental foundation for therapeutic strategies targeting Ro52/SSA production in pSS.
{"title":"Regulation of Ro52/SSA autoantigen by endoplasmic reticulum stress and ERK1/2-mTOR-autophagy signaling pathway in primary Sjögren disease","authors":"Qianwen Tian , Qi Xi , Qiaolin Zhang , Yun Chen , Yunxin Zhang , Fuxue Kuang , Lejie Sun , Song Peng , Huaxun Wu","doi":"10.1016/j.clim.2025.110655","DOIUrl":"10.1016/j.clim.2025.110655","url":null,"abstract":"<div><div>Primary Sjögren disease (pSS) is an autoimmune disease characterized primarily by predominant lymphocytic infiltration of the exocrine glands. While the etiopathogenesis of pSS remains unclear, current therapeutic strategies lack efficacy. In human submandibular gland epithelial cells (HSGECs), endoplasmic reticulum stress (ERS) induces apoptosis, leading to the cellular redistribution of Ro52/SSA autoantigens, the activation of the immune system, and the production of a large number of autoantibodies. Cells initiate autophagy to resist cellular damage caused by ERS and restore the normal physiological status. The ERK1/2-mTOR-autophagy signaling pathway has been implicated in numerous pathological conditions. In this study, an experimental Sjögren disease (ESS) mouse model was established to evaluate reduced protein levels and altered intracellular distribution of Ro52/SSA autoantigens through modulation of ERS and the ERK1/2-mTOR-autophagy pathway, resulting in diminished autoantibody production and ameliorated ESS symptoms. These findings provide an experimental foundation for therapeutic strategies targeting Ro52/SSA production in pSS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110655"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-31DOI: 10.1016/j.clim.2025.110632
Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen
Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.
{"title":"Natural history of clinical manifestations in activated phosphoinositide 3-kinase δ syndrome (APDS): Time-to-event analyses using the European Society for Immunodeficiencies-APDS registry","authors":"Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen","doi":"10.1016/j.clim.2025.110632","DOIUrl":"10.1016/j.clim.2025.110632","url":null,"abstract":"<div><div>Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110632"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-29DOI: 10.1016/j.clim.2025.110653
Fatima Hubaishi , Rami Karkout , Lydia Labrie , Raidan Mohammed Alyazidi , Magan Solomon , Haya Aldossary , Brian J. Ward , Elizabeth D. Fixman
Atopic dermatitis (AD) in infants is associated with increased risk of developing other allergic diseases, including asthma. This progression is known as atopic march (AM). We established a murine AM model by first inducing AD-like skin inflammation to house dust mite (HDM) allergen. Mice were subsequently challenged with HDM delivered to the lung. Our data show that epicutaneous sensitization with HDM increased serum IgE, ear thickness, and immune cell infiltration into the skin, accompanied by an increase in CD4+ tissue-resident memory T cells (Trm) in the lung. Following pulmonary HDM challenge, eosinophil influx and T2 inflammation were increased in the lung. Together, our data suggest communication between the skin and lung, where allergen sensitization on the skin increases lung Trm and amplifies the T2 allergic response to lung allergen challenge. This clinically relevant model could help identify novel targets for local interventions to reduce the progression of AD to asthma.
{"title":"Epicutaneous application of house dust mite induces allergic skin inflammation and atopic march to the lung upon airway allergen challenge","authors":"Fatima Hubaishi , Rami Karkout , Lydia Labrie , Raidan Mohammed Alyazidi , Magan Solomon , Haya Aldossary , Brian J. Ward , Elizabeth D. Fixman","doi":"10.1016/j.clim.2025.110653","DOIUrl":"10.1016/j.clim.2025.110653","url":null,"abstract":"<div><div>Atopic dermatitis (AD) in infants is associated with increased risk of developing other allergic diseases, including asthma. This progression is known as atopic march (AM). We established a murine AM model by first inducing AD-like skin inflammation to house dust mite (HDM) allergen. Mice were subsequently challenged with HDM delivered to the lung. Our data show that epicutaneous sensitization with HDM increased serum IgE, ear thickness, and immune cell infiltration into the skin, accompanied by an increase in CD4<sup>+</sup> tissue-resident memory T cells (Trm) in the lung. Following pulmonary HDM challenge, eosinophil influx and T2 inflammation were increased in the lung. Together, our data suggest communication between the skin and lung, where allergen sensitization on the skin increases lung Trm and amplifies the T2 allergic response to lung allergen challenge. This clinically relevant model could help identify novel targets for local interventions to reduce the progression of AD to asthma.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110653"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.clim.2025.110642
Josephine Diony Nanda , Tzong-Shiann Ho , Rahmat Dani Satria , Yung-Ting Wang , Chun-Hao Lai , Ya-Lan Lin , Chiou-Feng Lin
Serum cytokines and chemokines play a pivotal role in dengue immunopathogenesis and may serve as biomarkers of disease severity. This study aimed to identify applicable blood biomarkers during the acute stage of infection to support early severity evaluation using Principal Component Analysis (PCA)–based feature integration. Ninety-two dengue patients were consecutively enrolled from hospital admissions with laboratory-confirmed dengue during the 2015–2017 epidemic. Only those with NS1-positive or PCR-positive cases were included in this study, spanning asymptomatic, symptomatic, and severe cases, which were assessed for hematological, viral, and cytokine/chemokine parameters. Key variables—platelet count, GPT, creatinine, NS1, NST, IL-18, RANTES, IL-6, IFN-α2, and IL-7—were incorporated into a Prediction Panel. Validation showed that several biomarker combinations achieved up to 90 % accuracy in distinguishing severity groups, while others reached ∼70 %. Principal component analysis further refined the panel, showing accuracy above 90 % when NS1 or NST were included (A–B: 92.1 %, A–C: up to 91.8 %). These findings highlight the potential of an integrated biomarker-based Prediction Panel for early and reliable assessment of dengue severity within the first week of illness.
{"title":"An integrated biomarker panel for early computational prediction of dengue severity during the acute phase","authors":"Josephine Diony Nanda , Tzong-Shiann Ho , Rahmat Dani Satria , Yung-Ting Wang , Chun-Hao Lai , Ya-Lan Lin , Chiou-Feng Lin","doi":"10.1016/j.clim.2025.110642","DOIUrl":"10.1016/j.clim.2025.110642","url":null,"abstract":"<div><div>Serum cytokines and chemokines play a pivotal role in dengue immunopathogenesis and may serve as biomarkers of disease severity. This study aimed to identify applicable blood biomarkers during the acute stage of infection to support early severity evaluation using Principal Component Analysis (PCA)–based feature integration. Ninety-two dengue patients were consecutively enrolled from hospital admissions with laboratory-confirmed dengue during the 2015–2017 epidemic. Only those with NS1-positive or PCR-positive cases were included in this study, spanning asymptomatic, symptomatic, and severe cases, which were assessed for hematological, viral, and cytokine/chemokine parameters. Key variables—platelet count, GPT, creatinine, NS1, NST, IL-18, RANTES, IL-6, IFN-α2, and IL-7—were incorporated into a Prediction Panel. Validation showed that several biomarker combinations achieved up to 90 % accuracy in distinguishing severity groups, while others reached ∼70 %. Principal component analysis further refined the panel, showing accuracy above 90 % when NS1 or NST were included (A–B: 92.1 %, A–C: up to 91.8 %). These findings highlight the potential of an integrated biomarker-based Prediction Panel for early and reliable assessment of dengue severity within the first week of illness.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110642"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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