Primary central nervous system vasculitis, also known as primary angiitis of CNS (PACNS), is a rare and heterogeneous inflammatory disorder of blood vessels restricted to the central nervous system. The most common presenting symptoms are headache, focal neurological deficits, and altered cognition. Subtypes of PACNS can have different presentations. Diagnosis is challenging due to clinical, imaging, and histopathological heterogeneity, as well as numerous mimics. The goal of diagnostic work-up is to establish that the neurological presentation is due to an underlying vasculitis based on angiographic or histopathologic features and to exclude infection, systemic vasculitis, or other mimics. Treatment is based on anecdotal evidence and consensus, and includes glucocorticoids and cyclophosphamide for induction of remission, as well as mycophenolate mofetil, rituximab, azathioprine, and methotrexate for maintenance therapy. Only two-thirds of the patients achieve a good neurological outcome. A detailed understanding of the etiopathogenesis and heterogeneity will be necessary for developing more effective biomarkers, precision therapies, and improved outcomes.
{"title":"Primary angiitis of the central nervous system","authors":"Sushmitha Meghashyam , Fatema J Serajee , Aviraag V Prakash , Denise Altinok , AHM Mahbubul Huq","doi":"10.1016/j.coi.2025.102691","DOIUrl":"10.1016/j.coi.2025.102691","url":null,"abstract":"<div><div>Primary central nervous system vasculitis, also known as primary angiitis of CNS (PACNS), is a rare and heterogeneous inflammatory disorder of blood vessels restricted to the central nervous system. The most common presenting symptoms are headache, focal neurological deficits, and altered cognition. Subtypes of PACNS can have different presentations. Diagnosis is challenging due to clinical, imaging, and histopathological heterogeneity, as well as numerous mimics. The goal of diagnostic work-up is to establish that the neurological presentation is due to an underlying vasculitis based on angiographic or histopathologic features and to exclude infection, systemic vasculitis, or other mimics. Treatment is based on anecdotal evidence and consensus, and includes glucocorticoids and cyclophosphamide for induction of remission, as well as mycophenolate mofetil, rituximab, azathioprine, and methotrexate for maintenance therapy. Only two-thirds of the patients achieve a good neurological outcome. A detailed understanding of the etiopathogenesis and heterogeneity will be necessary for developing more effective biomarkers, precision therapies, and improved outcomes.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102691"},"PeriodicalIF":5.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.coi.2025.102690
Marcin Radziszewski , Kandice L Tessneer , Christopher J Lessard
Sjögren’s disease (SjD) is the second most common systemic autoimmune disease in the United States. SjD patients are predominantly women 30–50 years of age and exhibit heterogeneous clinical manifestations, including symptoms of extensive dryness, chronic fatigue, and joint pain, and various major organ involvement. Late onset, clinical heterogeneity, and limited mechanistic understanding of its etiology frequently lead to delayed or misdiagnosis. Although the etiology of SjD is unclear, candidate gene studies and population-based genome-wide association studies suggest that SjD results from an interplay between genetics and environment. Defining the genetic susceptibility of SjD remains an important research focus to improve the understanding of SjD etiology and the development of diagnostic and treatment options. Unfortunately, the genetic understanding of SjD lags far behind that of other related autoimmune diseases. This review provides a brief history of key milestones in the field of SjD genetics and highlights several areas of future research that will bolster the discovery power of ongoing genetic studies and define the underlying mechanisms that drive disease etiology.
{"title":"The power of genetics in decoding Sjögren’s disease: current status and future development","authors":"Marcin Radziszewski , Kandice L Tessneer , Christopher J Lessard","doi":"10.1016/j.coi.2025.102690","DOIUrl":"10.1016/j.coi.2025.102690","url":null,"abstract":"<div><div>Sjögren’s disease (SjD) is the second most common systemic autoimmune disease in the United States. SjD patients are predominantly women 30–50 years of age and exhibit heterogeneous clinical manifestations, including symptoms of extensive dryness, chronic fatigue, and joint pain, and various major organ involvement. Late onset, clinical heterogeneity, and limited mechanistic understanding of its etiology frequently lead to delayed or misdiagnosis. Although the etiology of SjD is unclear, candidate gene studies and population-based genome-wide association studies suggest that SjD results from an interplay between genetics and environment. Defining the genetic susceptibility of SjD remains an important research focus to improve the understanding of SjD etiology and the development of diagnostic and treatment options. Unfortunately, the genetic understanding of SjD lags far behind that of other related autoimmune diseases. This review provides a brief history of key milestones in the field of SjD genetics and highlights several areas of future research that will bolster the discovery power of ongoing genetic studies and define the underlying mechanisms that drive disease etiology.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102690"},"PeriodicalIF":5.8,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent advancements in microbiome research have revealed the restorative capacities of postbiotics, including indole and its derivatives generated via bacterial tryptophan metabolism. Widespread in prokaryotic and eukaryotic communities, indole and its derivatives are uniquely suited to promote host physiology and homeostasis at the host/microbe interface. In addition to suppressing the bacterial pathogenesis, the antioxidant, anti-inflammatory, antidiabetic, antihypertensive, immunomodulatory, and metabolic activities of indole and its derivatives make these postbiotics an attractive therapeutic option. However, their clinical translation is impeded by pharmacokinetic constraints, structural promiscuity, and formulation difficulties. This review examines the current status of indole bioactivities, identifies translational challenges, and suggests the use of artificial intelligence as a method for establishing a comprehensive framework for future translational development.
{"title":"Toward indole postbiotics precision therapy via AI-powered drug delivery technologies","authors":"Puccetti Matteo , Pariano Marilena , Wojtylo Paulina Anna , Ricci Maurizio , Stefano Giovagnoli","doi":"10.1016/j.coi.2025.102692","DOIUrl":"10.1016/j.coi.2025.102692","url":null,"abstract":"<div><div>Recent advancements in microbiome research have revealed the restorative capacities of postbiotics, including indole and its derivatives generated via bacterial tryptophan metabolism. Widespread in prokaryotic and eukaryotic communities, indole and its derivatives are uniquely suited to promote host physiology and homeostasis at the host/microbe interface. In addition to suppressing the bacterial pathogenesis, the antioxidant, anti-inflammatory, antidiabetic, antihypertensive, immunomodulatory, and metabolic activities of indole and its derivatives make these postbiotics an attractive therapeutic option. However, their clinical translation is impeded by pharmacokinetic constraints, structural promiscuity, and formulation difficulties. This review examines the current status of indole bioactivities, identifies translational challenges, and suggests the use of artificial intelligence as a method for establishing a comprehensive framework for future translational development.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102692"},"PeriodicalIF":5.8,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.coi.2025.102684
Nicolle Sweeney , Yemil Atisha-Fregoso , Rita Pozovskiy , Lauren Higdon , Mark Anderson , Betty Diamond , William M Ridgway
Autoimmune diseases have, until recently, been treated with relatively broad immunosuppressive regimens. Newer, more focused monoclonal antibody therapies directed to specific targets, for example, anti-TNF or anti-B cell therapies, can produce significant immunosuppression. ‘Remission’ of autoimmune disease that requires ongoing immunosuppression is not an ideal solution. We define a ‘cure’ for autoimmunity as: resolution of disease without ongoing immunosuppressive therapy. Herein, we discuss the possibilities of such a cure, the mechanisms behind such approaches, and obstacles in the setting of representative systemic (systemic lupus erythematosus, or SLE) and organ-specific (type 1 diabetes, T1D) autoimmune diseases. ‘Cure’ of autoimmunity is a remarkably difficult goal and, as illustrated here, will require detailed scientific understanding of each autoimmune disease, even beyond the remarkable advances achieved to date. The basic distinction between autoimmune diseases, in which the target organ is largely destroyed at clinical onset (e.g. T1D), and systemic diseases affecting multiple organs strongly affects how progress can be made towards a cure. In the case of systemic disease, obtaining exact further knowledge of the role of immune cell subsets (e.g. short-lived plasma cells in SLE) is critical. In organ-specific autoimmunity, such as in T1D, improved preclinical detection and characterization of the preclinical immune pathology will be essential.
{"title":"Can we cure autoimmunity?","authors":"Nicolle Sweeney , Yemil Atisha-Fregoso , Rita Pozovskiy , Lauren Higdon , Mark Anderson , Betty Diamond , William M Ridgway","doi":"10.1016/j.coi.2025.102684","DOIUrl":"10.1016/j.coi.2025.102684","url":null,"abstract":"<div><div>Autoimmune diseases have, until recently, been treated with relatively broad immunosuppressive regimens. Newer, more focused monoclonal antibody therapies directed to specific targets, for example, anti-TNF or anti-B cell therapies, can produce significant immunosuppression. ‘Remission’ of autoimmune disease that requires ongoing immunosuppression is not an ideal solution. We define a ‘cure’ for autoimmunity as: <em>resolution of disease without ongoing immunosuppressive therapy</em>. Herein, we discuss the possibilities of such a cure, the mechanisms behind such approaches, and obstacles in the setting of representative systemic (systemic lupus erythematosus, or SLE) and organ-specific (type 1 diabetes, T1D) autoimmune diseases. ‘Cure’ of autoimmunity is a remarkably difficult goal and, as illustrated here, will require detailed scientific understanding of each autoimmune disease, even beyond the remarkable advances achieved to date. The basic distinction between autoimmune diseases, in which the target organ is largely destroyed at clinical onset (e.g. T1D), and systemic diseases affecting multiple organs strongly affects how progress can be made towards a cure. In the case of systemic disease, obtaining exact further knowledge of the role of immune cell subsets (e.g. short-lived plasma cells in SLE) is critical. In organ-specific autoimmunity, such as in T1D, improved preclinical detection and characterization of the preclinical immune pathology will be essential.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102684"},"PeriodicalIF":5.8,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1016/j.coi.2025.102689
Jonas Lowack , Alexander PJ Vlaar , Robert B Klanderman , Anna-Linda Peters
Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are leading causes of transfusion-related morbidity and mortality. Despite distinct diagnostic criteria, both syndromes present similarly with respiratory distress and pulmonary edema. In recent research, they increasingly appear to share pathophysiological and immunological features. In this review, we discuss current evidence supporting a spectrum model of pulmonary transfusion reactions, spanning hydrostatic to permeability edema. We highlight key immunological mechanisms in TRALI, including Fc-receptor or complement engagement, and cytokine responses, and explore emerging evidence of immune involvement in TACO. To differentiate, the anti-inflammatory cytokine interleukin (IL)-10 and pro-inflammatory IL-6 emerge as potential biomarkers with diagnostic and therapeutic implications. The underdiagnosis of reverse TRALI and TRALI/TACO overlap further highlights the need for additional mechanistic insight and improved diagnostics. Future work should focus on biomarker-guided phenotyping to improve clinical differentiation and treatment strategies for transfusion-related respiratory complications as a spectrum disorder.
{"title":"Pulmonary transfusion reactions as an immunological spectrum disorder","authors":"Jonas Lowack , Alexander PJ Vlaar , Robert B Klanderman , Anna-Linda Peters","doi":"10.1016/j.coi.2025.102689","DOIUrl":"10.1016/j.coi.2025.102689","url":null,"abstract":"<div><div>Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are leading causes of transfusion-related morbidity and mortality. Despite distinct diagnostic criteria, both syndromes present similarly with respiratory distress and pulmonary edema. In recent research, they increasingly appear to share pathophysiological and immunological features. In this review, we discuss current evidence supporting a spectrum model of pulmonary transfusion reactions, spanning hydrostatic to permeability edema. We highlight key immunological mechanisms in TRALI, including Fc-receptor or complement engagement, and cytokine responses, and explore emerging evidence of immune involvement in TACO. To differentiate, the anti-inflammatory cytokine interleukin (IL)-10 and pro-inflammatory IL-6 emerge as potential biomarkers with diagnostic and therapeutic implications. The underdiagnosis of reverse TRALI and TRALI/TACO overlap further highlights the need for additional mechanistic insight and improved diagnostics. Future work should focus on biomarker-guided phenotyping to improve clinical differentiation and treatment strategies for transfusion-related respiratory complications as a spectrum disorder.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102689"},"PeriodicalIF":5.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.coi.2025.102688
Hideaki Uchida , Xuesong Wu , Yan Zhou , Jie Zheng , Heike Wulff , Samuel T Hwang
Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte growth, immune dysfunction, and a weakened skin barrier. Affecting 2–3% of the global population, it lowers quality of life and is linked to systemic conditions. Though treatments have improved, many patients still lack effective options. Recent research emphasizes the critical role of ion channels, especially cation channels, in psoriasis. These channels influence keratinocyte proliferation, differentiation, immune responses, and apoptosis. Dysregulation of calcium, potassium, sodium, and chloride channels contributes to inflammation, skin barrier issues, and keratinocyte malfunction. For instance, transient receptor potential channels affect inflammation and differentiation, while voltage-gated potassium channels impact immune cell activity and cytokine release. This review summarizes how cation channels contribute to psoriasis and highlights their therapeutic potential, offering new directions for targeted treatments aimed at restoring skin integrity and reducing inflammation.
{"title":"Role of ion channels in immune regulation of psoriasis","authors":"Hideaki Uchida , Xuesong Wu , Yan Zhou , Jie Zheng , Heike Wulff , Samuel T Hwang","doi":"10.1016/j.coi.2025.102688","DOIUrl":"10.1016/j.coi.2025.102688","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte growth, immune dysfunction, and a weakened skin barrier. Affecting 2–3% of the global population, it lowers quality of life and is linked to systemic conditions. Though treatments have improved, many patients still lack effective options. Recent research emphasizes the critical role of ion channels, especially cation channels, in psoriasis. These channels influence keratinocyte proliferation, differentiation, immune responses, and apoptosis. Dysregulation of calcium, potassium, sodium, and chloride channels contributes to inflammation, skin barrier issues, and keratinocyte malfunction. For instance, transient receptor potential channels affect inflammation and differentiation, while voltage-gated potassium channels impact immune cell activity and cytokine release. This review summarizes how cation channels contribute to psoriasis and highlights their therapeutic potential, offering new directions for targeted treatments aimed at restoring skin integrity and reducing inflammation.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102688"},"PeriodicalIF":5.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.coi.2025.102683
José López-Bucio , Kirán Rubí Jiménez-Vázquez , Esperanza Martínez-Romero
The production of indole-3-acetic acid (IAA, auxin) is universal in microbes and plants, and contributes to human wellness, acting as an anticancer and anti-inflammatory agent. This review highlights the ubiquity of IAA production by microbes and plants, as well as its role in human health. A high-fat diet decreases IAA levels in the intestine and serum, whereas intake of IAA as part of plant or microbial-derived food, or engineering the endogenous microbiome with IAA-producing bacteria, offers suitable alternatives against diseases. The aryl hydrocarbon receptor found in immune cells in the intestine has affinities for IAA and regulates both adaptive and innate immune responses. In plants, IAA receptors are well known, as well as the molecular responses elicited. Clearly, IAA is a key molecule in plant and human health, and plant and human health are interrelated.
{"title":"Indole-3-acetic acid from plants and microbes in human health","authors":"José López-Bucio , Kirán Rubí Jiménez-Vázquez , Esperanza Martínez-Romero","doi":"10.1016/j.coi.2025.102683","DOIUrl":"10.1016/j.coi.2025.102683","url":null,"abstract":"<div><div>The production of indole-3-acetic acid (IAA, auxin) is universal in microbes and plants, and contributes to human wellness, acting as an anticancer and anti-inflammatory agent. This review highlights the ubiquity of IAA production by microbes and plants, as well as its role in human health. A high-fat diet decreases IAA levels in the intestine and serum, whereas intake of IAA as part of plant or microbial-derived food, or engineering the endogenous microbiome with IAA-producing bacteria, offers suitable alternatives against diseases. The aryl hydrocarbon receptor found in immune cells in the intestine has affinities for IAA and regulates both adaptive and innate immune responses. In plants, IAA receptors are well known, as well as the molecular responses elicited. Clearly, IAA is a key molecule in plant and human health, and plant and human health are interrelated.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102683"},"PeriodicalIF":5.8,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.coi.2025.102685
Cameron S Bader , Everett H Meyer , Robert S Negrin
Regulatory T cells (Tregs) are a rare subset of T cells that are potent regulators of the immune system. As a result, the use of Tregs to prevent undesired immune activation and to re-establish immune balance is an attractive cellular therapy approach. In hematopoietic cell transplantation (HCT), there has been significant interest in using Tregs to prevent graft-versus-host disease (GVHD), which occurs when donor alloreactive T cells recognize recipient HLA- or other minor transplantation antigens as non-self. There is a critical unmet need for novel strategies to prevent GVHD since as many as 50% of patients will develop clinically significant GVHD with current therapies. Evidence from preclinical murine models and early-phase human studies suggests that an additional benefit to Treg cellular therapy in HCT is the apparent maintenance of pathogenic immunity and graft-versus-tumor effects, which are required to prevent leukemia relapse. While the major limiting factor for Treg-based therapies has been the rarity of these cells, novel methods to improve Treg isolation and expansion have demonstrated feasibility for implementation of these strategies in the clinic. Moreover, genetic engineering of Tregs has been shown to be a promising strategy to improve their specificity, longevity, and function. Clinical trials have established that such approaches are feasible and can be effective in both human leukocyte antigen (HLA)-matched and haplo-matched settings. In this review, we describe proposed mechanisms for Treg control of alloreactivity, modern methods for Treg isolation and expansion, the history of Treg clinical trials for GVHD prevention, and the horizon for Treg cellular therapy.
{"title":"Regulatory T cell approaches for graft-versus-host disease prevention","authors":"Cameron S Bader , Everett H Meyer , Robert S Negrin","doi":"10.1016/j.coi.2025.102685","DOIUrl":"10.1016/j.coi.2025.102685","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) are a rare subset of T cells that are potent regulators of the immune system. As a result, the use of Tregs to prevent undesired immune activation and to re-establish immune balance is an attractive cellular therapy approach. In hematopoietic cell transplantation (HCT), there has been significant interest in using Tregs to prevent graft-versus-host disease (GVHD), which occurs when donor alloreactive T cells recognize recipient HLA- or other minor transplantation antigens as non-self. There is a critical unmet need for novel strategies to prevent GVHD since as many as 50% of patients will develop clinically significant GVHD with current therapies. Evidence from preclinical murine models and early-phase human studies suggests that an additional benefit to Treg cellular therapy in HCT is the apparent maintenance of pathogenic immunity and graft-versus-tumor effects, which are required to prevent leukemia relapse. While the major limiting factor for Treg-based therapies has been the rarity of these cells, novel methods to improve Treg isolation and expansion have demonstrated feasibility for implementation of these strategies in the clinic. Moreover, genetic engineering of Tregs has been shown to be a promising strategy to improve their specificity, longevity, and function. Clinical trials have established that such approaches are feasible and can be effective in both human leukocyte antigen (HLA)-matched and haplo-matched settings. In this review, we describe proposed mechanisms for Treg control of alloreactivity, modern methods for Treg isolation and expansion, the history of Treg clinical trials for GVHD prevention, and the horizon for Treg cellular therapy.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102685"},"PeriodicalIF":5.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.coi.2025.102686
Anna Duval , Julia Roquigny , Véronique Frémeaux-Bacchi
Complement inhibition has revolutionized the management of hemolytic diseases by targeting the underlying drivers of red blood cell destruction in disorders such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and cold agglutinin disease. Recent advances have expanded the therapeutic landscape beyond terminal C5 inhibition to proximal strategies targeting C3, factor B, and factor D. These newer agents — such as pegcetacoplan, iptacopan, and danicopan — not only control intravascular hemolysis but also address extravascular hemolysis and offer oral or subcutaneous alternatives. In cold agglutinin disease, the efficacy of the classical pathway inhibitor sutimlimab provides compelling evidence for the therapeutic value of targeting early initiating molecules of the complement cascade. For clinicians, these innovations provide personalized treatment choices based on disease phenotype, hemolysis profile, patient preference, and risk stratification. The evolving complement inhibitor arsenal enables optimized, targeted care and pathway-specific interventions in hemolytic conditions.
{"title":"Complement-targeting therapies in hemolytic diseases","authors":"Anna Duval , Julia Roquigny , Véronique Frémeaux-Bacchi","doi":"10.1016/j.coi.2025.102686","DOIUrl":"10.1016/j.coi.2025.102686","url":null,"abstract":"<div><div>Complement inhibition has revolutionized the management of hemolytic diseases by targeting the underlying drivers of red blood cell destruction in disorders such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and cold agglutinin disease. Recent advances have expanded the therapeutic landscape beyond terminal C5 inhibition to proximal strategies targeting C3, factor B, and factor D. These newer agents — such as pegcetacoplan, iptacopan, and danicopan — not only control intravascular hemolysis but also address extravascular hemolysis and offer oral or subcutaneous alternatives. In cold agglutinin disease, the efficacy of the classical pathway inhibitor sutimlimab provides compelling evidence for the therapeutic value of targeting early initiating molecules of the complement cascade. For clinicians, these innovations provide personalized treatment choices based on disease phenotype, hemolysis profile, patient preference, and risk stratification. The evolving complement inhibitor arsenal enables optimized, targeted care and pathway-specific interventions in hemolytic conditions.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102686"},"PeriodicalIF":5.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.coi.2025.102687
Haiyu Wang , Daan J van den Brink , Balthasar A Heesters , Paul WHI Parren , Leendert A Trouw
Excessive complement activation represents a major pathogenic mechanism for a range of serious human diseases. Complement-inhibitory therapeutics have been approved for a number of rare and ultra-rare conditions, with several others in clinical development. The vast majority of these complement-targeted drugs act via systemic inhibition that requires high dosing with associated high cost and, in addition, carries increased risks for developing life-threatening infectious diseases. Local complement inhibition, allowing lower dosing, lower costs, and a better safety profile, therefore, represents an attractive novel strategy. Several approaches to achieve local complement inhibition, including local application and site-specific targeting, are being assessed. This review will primarily focus on the tissue-specific targeting using antibody technologies for approaches both in preclinical and clinical development, and discuss its advantages and limitations. Overall, we see great promise for an upcoming generation of targeted complement inhibitors that enable selective inhibition of complement exclusively at the site of disease.
{"title":"Local complement inhibition by selective precision-targeted therapies","authors":"Haiyu Wang , Daan J van den Brink , Balthasar A Heesters , Paul WHI Parren , Leendert A Trouw","doi":"10.1016/j.coi.2025.102687","DOIUrl":"10.1016/j.coi.2025.102687","url":null,"abstract":"<div><div>Excessive complement activation represents a major pathogenic mechanism for a range of serious human diseases. Complement-inhibitory therapeutics have been approved for a number of rare and ultra-rare conditions, with several others in clinical development. The vast majority of these complement-targeted drugs act via systemic inhibition that requires high dosing with associated high cost and, in addition, carries increased risks for developing life-threatening infectious diseases. Local complement inhibition, allowing lower dosing, lower costs, and a better safety profile, therefore, represents an attractive novel strategy. Several approaches to achieve local complement inhibition, including local application and site-specific targeting, are being assessed. This review will primarily focus on the tissue-specific targeting using antibody technologies for approaches both in preclinical and clinical development, and discuss its advantages and limitations. Overall, we see great promise for an upcoming generation of targeted complement inhibitors that enable selective inhibition of complement exclusively at the site of disease.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102687"},"PeriodicalIF":5.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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