Pub 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":"2025-12-16","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 : 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 : 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":"2025-12-11","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}
The type I IFN response plays an important role in the immune defence against invading pathogens and in certain autoinflammatory diseases. In this study, a flow cytometry-based assay to measure ISG15 production in response to stimulation with various TLR ligands and IFNα was developed. PBMCs of healthy controls or patients were stimulated with TLR7/8, TLR3 and TLR9 ligands and IFNα2 whereafter ISG15 expression was measured. The ability of the assay to analyse TLR-dependent type I IFN induction and type I IFN-dependent JAK/STAT activation was verified by inhibition of ISG15 induction by a TBK1/IKKε inhibitor and a JAK1 inhibitor, respectively. TLR7/8 ligand- and TLR9 ligand-induced ISG15 production but not IFNα2-induced ISG15 production was abolished in a patient with AR IRF7 deficiency. IFNα2-induced ISG15 expression was abolished by serum containing neutralizing anti-IFNα2 autoantibodies. The flow cytometry-based ISG15 induction assay can be applied to screen for defects in the type I IFN response.
{"title":"Development and validation of a flow cytometry-based ISG15 induction assay to monitor the type I interferon response","authors":"Birthe Michiels , Rudi Beyaert , Jens Staal , Doreen Dillaerts , Maaike Cockx , Glynis Frans , Birgit Timmermans , Natalie Lorent , Isabelle Meyts , Xavier Bossuyt","doi":"10.1016/j.clim.2025.110654","DOIUrl":"10.1016/j.clim.2025.110654","url":null,"abstract":"<div><div>The type I IFN response plays an important role in the immune defence against invading pathogens and in certain autoinflammatory diseases. In this study, a flow cytometry-based assay to measure ISG15 production in response to stimulation with various TLR ligands and IFNα was developed. PBMCs of healthy controls or patients were stimulated with TLR7/8, TLR3 and TLR9 ligands and IFNα2 whereafter ISG15 expression was measured. The ability of the assay to analyse TLR-dependent type I IFN induction and type I IFN-dependent JAK/STAT activation was verified by inhibition of ISG15 induction by a TBK1/IKKε inhibitor and a JAK1 inhibitor, respectively. TLR7/8 ligand- and TLR9 ligand-induced ISG15 production but not IFNα2-induced ISG15 production was abolished in a patient with AR IRF7 deficiency. IFNα2-induced ISG15 expression was abolished by serum containing neutralizing anti-IFNα2 autoantibodies. The flow cytometry-based ISG15 induction assay can be applied to screen for defects in the type I IFN response.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110654"},"PeriodicalIF":3.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676231","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 : 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":"2025-11-29","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 : 2025-11-25DOI: 10.1016/j.clim.2025.110646
Pengbo Yang , Huhe Bao , Guanwen Sun , Yaxing Zhang
Background
Type 1 diabetes (T1DM) is characterized by autoimmune destruction of pancreatic β-cells and systemic immune dysregulation, yet the cellular networks driving disease progression and their potential link to diabetic complications remain unclear.
Methods
We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from 46 stage 3 T1DM patients and 31 matched controls, integrating transcriptomic, cellular interaction, and functional enrichment analyses.
Results
Unsupervised clustering of 87,542 cells revealed profound immune dysregulation in T1DM, including cytotoxic CD8+ T cell expansion (70 % increase) and Treg depletion (>50 % reduction). CD8+ T cells exhibited hyperactivation of cytotoxic effectors (GNLY, GZMB) and inflammatory mediators (IL32, S100A4), alongside suppressed regulatory genes (FOXP3, IL2RA). Cell-cell communication analysis identified amplified GALECTIN-CD44 signaling between monocytes/DCs and CD8+ T/NK cells, driving proinflammatory crosstalk. Strikingly, a novel exhausted CD4+ subset (PDCD1+, LAG3+) emerged exclusively in T1DM.
Conclusion
Our findings establish CD8+ T cells as central orchestrators of T1DM pathogenesis through synergistic cytotoxic hyperactivity and regulatory collapse. The identified GALECTIN-CD44 axis and JAK-STAT/TGF-β imbalances may extend beyond pancreatic autoimmunity, providing mechanistic insights into systemic complications (e.g., impaired wound healing and chronic inflammation) observed in diabetic patients. These dysregulated networks offer novel therapeutic targets for restoring immune homeostasis in T1DM and its associated comorbidities.
{"title":"Single-cell dissection of CD8+ T cell-driven immune dysregulation in type 1 diabetes mellitus: Mechanistic links to diabetic foot pathogenesis","authors":"Pengbo Yang , Huhe Bao , Guanwen Sun , Yaxing Zhang","doi":"10.1016/j.clim.2025.110646","DOIUrl":"10.1016/j.clim.2025.110646","url":null,"abstract":"<div><h3>Background</h3><div>Type 1 diabetes (T1DM) is characterized by autoimmune destruction of pancreatic β-cells and systemic immune dysregulation, yet the cellular networks driving disease progression and their potential link to diabetic complications remain unclear.</div></div><div><h3>Methods</h3><div>We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from 46 stage 3 T1DM patients and 31 matched controls, integrating transcriptomic, cellular interaction, and functional enrichment analyses.</div></div><div><h3>Results</h3><div>Unsupervised clustering of 87,542 cells revealed profound immune dysregulation in T1DM, including cytotoxic CD8+ T cell expansion (70 % increase) and Treg depletion (>50 % reduction). CD8+ T cells exhibited hyperactivation of cytotoxic effectors (GNLY, GZMB) and inflammatory mediators (IL32, S100A4), alongside suppressed regulatory genes (FOXP3, IL2RA). Cell-cell communication analysis identified amplified GALECTIN-CD44 signaling between monocytes/DCs and CD8+ T/NK cells, driving proinflammatory crosstalk. Strikingly, a novel exhausted CD4+ subset (PDCD1+, LAG3+) emerged exclusively in T1DM.</div></div><div><h3>Conclusion</h3><div>Our findings establish CD8+ T cells as central orchestrators of T1DM pathogenesis through synergistic cytotoxic hyperactivity and regulatory collapse. The identified GALECTIN-CD44 axis and JAK-STAT/TGF-β imbalances may extend beyond pancreatic autoimmunity, providing mechanistic insights into systemic complications (e.g., impaired wound healing and chronic inflammation) observed in diabetic patients. These dysregulated networks offer novel therapeutic targets for restoring immune homeostasis in T1DM and its associated comorbidities.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110646"},"PeriodicalIF":3.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623447","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}
{"title":"Remaining molecular scarring in the skin of patients with psoriasis: What are the reversal factors?","authors":"Parvaneh Hatami , Hamed Nicknam Asl , Zeinab Aryanian , Azadeh Khayyat , Mona Homayouni , Arash Mostaghimi","doi":"10.1016/j.clim.2025.110645","DOIUrl":"10.1016/j.clim.2025.110645","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110645"},"PeriodicalIF":3.8,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623444","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":"2025-11-23","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 : 2025-11-22DOI: 10.1016/j.clim.2025.110643
Ahmed Salem Al-Dhahi , Hayder M. Al-kuraishy , Nawar R. Hussain , Mohamed N. Fawzy , Mubarak Alruwaili , Huda J. Waheed , Ali I. Al-Gareeb , Ali K. Albuhadily , Gaber El-Saber Batiha
Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease of the central nervous system (CNS). The cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) axis plays a complex, dual role in its pathogenesis. Although its upregulation typically induces neuroinflammation, oligodendrocyte apoptosis, and demyelination, certain PGE2 receptors (EP2/EP4) can also mediate protective effects. In experimental models, inhibiting COX-2 (using celecoxib or meloxicam) or blocking pro-inflammatory receptors (EP1/EP3) alleviates disease pathology by reducing immune cell infiltration and cytokine production and protecting oligodendrocytes via both COX-2-dependent and independent mechanisms. This review discusses the potential of selectively targeting the detrimental effects of the COX-2/PGE2 axis (such as EP1/EP3 signaling) while preserving protective pathways as a sophisticated therapeutic strategy for MS. However, cardiovascular risks limit the clinical translation of COX-2 inhibitors, necessitating the development of safer, more precise modulation of this pathway.
{"title":"The dual role of the COX-2/PGE2 Axis in multiple sclerosis: From pathogenesis to pharmacological inhibition","authors":"Ahmed Salem Al-Dhahi , Hayder M. Al-kuraishy , Nawar R. Hussain , Mohamed N. Fawzy , Mubarak Alruwaili , Huda J. Waheed , Ali I. Al-Gareeb , Ali K. Albuhadily , Gaber El-Saber Batiha","doi":"10.1016/j.clim.2025.110643","DOIUrl":"10.1016/j.clim.2025.110643","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease of the central nervous system (CNS). The cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) axis plays a complex, dual role in its pathogenesis. Although its upregulation typically induces neuroinflammation, oligodendrocyte apoptosis, and demyelination, certain PGE2 receptors (EP2/EP4) can also mediate protective effects. In experimental models, inhibiting COX-2 (using celecoxib or meloxicam) or blocking pro-inflammatory receptors (EP1/EP3) alleviates disease pathology by reducing immune cell infiltration and cytokine production and protecting oligodendrocytes via both COX-2-dependent and independent mechanisms. This review discusses the potential of selectively targeting the detrimental effects of the COX-2/PGE2 axis (such as EP1/EP3 signaling) while preserving protective pathways as a sophisticated therapeutic strategy for MS. However, cardiovascular risks limit the clinical translation of COX-2 inhibitors, necessitating the development of safer, more precise modulation of this pathway.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110643"},"PeriodicalIF":3.8,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594799","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 : 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":"2025-11-19","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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