Pier Luigi Meroni , Enrico Capobianco , Francesco Tedesco
{"title":"Can we cure antiphospholipid syndrome?","authors":"Pier Luigi Meroni , Enrico Capobianco , Francesco Tedesco","doi":"10.1016/j.coi.2025.102610","DOIUrl":"10.1016/j.coi.2025.102610","url":null,"abstract":"<div><div>Antiphospholipid antibody syndrome (APS) is a vasculopathy with recurrent thrombosis and/or miscarriages mediated by autoantibodies against PL-binding proteins (aPL), mainly beta2glycoprotein I (β2GPI). While clotting is the key in vascular APS, thrombosis is not critical for placenta pathology. Despite that, anticoagulant/antiplatelet drugs are the leading treatments, but this is not a ‘one-size-fits-all’ therapy, and recurrences are reported. Additional therapies (e.g. antimalarials, statins) and a better characterization of the individual risk profile may improve the outcome. Nevertheless, we are still unable to ‘cure’ APS. The ideal target would be aPL suppression. However, immunosuppression or even B-cell therapies are not effective. Targeting CD38 on antibody-producing cells or anti-CD19 CAR-T cell therapy are promising alternatives, as well as the chimeric autoantigen receptor T cell therapy, due to the identification of β2GPI as an APS autoantigen. Further therapies aimed at improving clot lysis or affecting β2GPI/anti-β2GPI tissue complex formation are appealing preclinical perspectives.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102610"},"PeriodicalIF":5.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779611","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}
{"title":"Insights and perspectives into the discovery of complement-related biomarkers in cancer","authors":"Daniel Ajona , Janire Debersaques , Ruben Pio","doi":"10.1016/j.coi.2025.102633","DOIUrl":"10.1016/j.coi.2025.102633","url":null,"abstract":"<div><div>The complement system, a central component of innate immunity, is implicated in tumor biology, influencing processes such as tumor progression, immune evasion, and response to therapy. Numerous studies have identified alterations in complement effectors, activation products, regulatory proteins, and receptors in patients with cancer. These findings underscore the potential of complement-derived biomarkers for enhancing cancer diagnosis, prognosis, or treatment guidance across various oncology settings. However, despite substantial progress in discovery and early validation, no complement-related biomarker has yet been integrated into routine oncology practice. Key challenges in the field include the biological complexity of the complement system, variability in testing methods, and the lack of standardized protocols for sample collection, processing, and analysis. Addressing these issues is essential to ensure reliable and reproducible measurements. Moreover, the clinical utility of these biomarkers depends on their validation in real-world settings, as well as their integration with other molecular markers, advanced imaging, radiomics, and artificial intelligence tools. Advancing the development of harmonized assays and reference materials will be critical for the translation of complement biomarkers into clinical use in cancer. This review summarizes current knowledge on complement-related biomarkers in oncology, highlights technical and conceptual challenges, and discusses future directions to fully harness the potential of the complement system in cancer care.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102633"},"PeriodicalIF":5.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779522","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}
Pascal Pedini , Jacques Chiaroni , Christophe Picard
{"title":"Red blood cell alloimmunization immunogenetic risk factor","authors":"Pascal Pedini , Jacques Chiaroni , Christophe Picard","doi":"10.1016/j.coi.2025.102634","DOIUrl":"10.1016/j.coi.2025.102634","url":null,"abstract":"<div><div>Alloimmunization to blood group antigens is the result of a humoral immune response initiated by exposure to foreign antigens absent from the recipient's red blood cells (RBCs). Interestingly, not all individuals who receive mismatched RBC transfusions develop alloantibodies. Increasing evidence points to the role of the classical human leukocyte antigen (HLA) system in modulating this immune response. More recently, polymorphisms in nonclassical HLA molecules have been implicated in the regulation of inflammatory responses, particularly in patients with sickle cell disease. The role of natural fetomaternal microchimerism may also be a factor to consider in explaining individual variability in alloimmune response.</div><div>The genetic diversity of both RBC antigens and HLA across ethnic groups underscores the need for high-throughput sequencing technologies to improve donor–recipient matching. In the future, genotyping strategies should aim not only to assess individual risk for alloantibody development but also to guide the selection of compatible RBC units, thereby reducing the likelihood of alloimmunization.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102634"},"PeriodicalIF":5.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779612","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}
{"title":"The role of epigenetics in inflammatory memory","authors":"Yaqin Yu , Yueqi Qiu , Ming Zhao","doi":"10.1016/j.coi.2025.102630","DOIUrl":"10.1016/j.coi.2025.102630","url":null,"abstract":"<div><div>Inflammatory memory refers to the ability of an organism to mount a stronger or faster response upon re-exposure to similar inflammatory stimuli. This heightened sensitivity was once thought to be a unique characteristic of immune cells. However, recent studies have challenged this traditional view, revealing that inflammatory memory is a widely prevalent phenomenon that extends beyond immune cells to include nonimmune cells. These studies indicate that the formation and maintenance of inflammatory memory largely depend on the regulation of epigenetics. Epigenetics involves heritable changes in gene expression without altering the DNA sequence, including mechanisms such as DNA methylation and histone modifications. These modifications regulate gene transcription and influence the cellular response to inflammatory stimuli. In this review, we will discuss the epigenetic mechanisms of inflammatory memory in both immune and nonimmune cells, focusing on new mechanistic insights from the past few years, and briefly discuss the unknowns and future strategies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102630"},"PeriodicalIF":5.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769461","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}
{"title":"Immunological complications of blood transfusion: current insights and advances","authors":"Naveen Bansal , Manish Raturi , Charu Singh , Yashik Bansal","doi":"10.1016/j.coi.2025.102617","DOIUrl":"10.1016/j.coi.2025.102617","url":null,"abstract":"<div><div>Blood transfusion is integral to modern medicine but carries significant immunological risks. This review outlines key immune-mediated complications, including acute hemolytic transfusion reactions from ABO incompatibility, and febrile nonhemolytic reactions caused by cytokines or antileukocyte antibodies. Other reactions include allergic responses, anaphylaxis (notably in IgA-deficient patients), and transfusion-related acute lung injury — the leading cause of transfusion-related mortality. Delayed hemolytic reactions, alloimmunization-induced platelet refractoriness, transfusion-associated graft-versus-host disease, and post-transfusion purpura also contribute to morbidity. Transfusion-related immunomodulation may increase infection and cancer recurrence risks. Preventive measures such as leukoreduction, irradiation, extended antigen matching, and restrictive transfusion strategies are crucial. This review article emphasis the importance on the need for strict adherence to protocols, enhanced hemovigilance, and education, especially in resource-limited settings. This review article summarizes the various immunological complications of blood transfusion and the recent advances in their etiopathogenesis, prevention, mitigation, and future research direction.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102617"},"PeriodicalIF":5.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721011","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}
Meghan E Free , Dominic J Ciavatta , Ronald J Falk
{"title":"Can we cure vasculitis?","authors":"Meghan E Free , Dominic J Ciavatta , Ronald J Falk","doi":"10.1016/j.coi.2025.102618","DOIUrl":"10.1016/j.coi.2025.102618","url":null,"abstract":"<div><div>As with all autoimmune diseases, antineutrophil cytoplasmic autoantibody (ANCA) vasculitis cannot be cured by a singular approach. This complexity arises because autoimmune conditions typically result from multiple hits to the immune system — including genetic predisposition, environmental exposures, infections, and perturbations in adaptive and innate immunity. However, these multiple hits also offer opportunities to develop targeted, multipronged strategies aimed at achieving lasting remission or even cure. The field of ANCA vasculitis is unique because a subset of patients has successfully discontinued immunosuppression while maintaining remission. This challenges the long-standing belief and paradigm that autoimmunity necessitates lifelong immunosuppression therapy characterized by cycles of relapse and remission. These patients embody the potential for cure. By exploring theoretical pathways — such as early intervention to modulate innate immunity, restoring normal autoantigen production, enhancing immunoregulatory mechanisms, and eliminating autoreactive cells — we can begin to chart a detailed molecular and cellular roadmap. This approach aims to develop combination therapies that restore immune balance and ultimately transform the management of autoimmune vasculitis, moving toward the goal of durable remission and cure.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102618"},"PeriodicalIF":5.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721009","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}
{"title":"Complement system modulation in age-related macular degeneration: navigating failures, building future successes","authors":"Aliénor Vienne-Jumeau , Elodie Bousquet , Francine Behar-Cohen","doi":"10.1016/j.coi.2025.102616","DOIUrl":"10.1016/j.coi.2025.102616","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in elderly populations across developed countries. Complement system dysregulation has been implicated in AMD onset and evolution. Complement inhibition therapies have been authorized in the USA as the primary treatment for geographic atrophy, the dry form of AMD. They have shown moderate efficacy in slowing geographic atrophy lesion growth but have not demonstrated improvements in visual function. Challenges remain, including the optimal timing of intervention, delivery routes, safety concerns, the lack of sensitive biomarkers to assess efficacy and guide patient selection, and variability in therapeutic response.</div><div>Complement modulation represents a promising yet complex therapeutic avenue in AMD. Future success will require earlier intervention, precision medicine approaches integrating genetic and imaging biomarkers, and the exploration of combination or gene-based therapies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102616"},"PeriodicalIF":5.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721010","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}
{"title":"Neuroimmune mechanisms of neuropsychiatric systemic lupus erythematosus","authors":"Stacie L Lin , Michael C Carroll","doi":"10.1016/j.coi.2025.102608","DOIUrl":"10.1016/j.coi.2025.102608","url":null,"abstract":"<div><div>In systemic lupus erythematosus (SLE), chronic autoimmunity and sustained inflammation can lead to the development of neuropsychiatric lupus (NPSLE) in up to 80% of patients. Elevated interferon-alpha (IFNα) is detected in serum and cerebrospinal fluid, making it a major focus in studies investigating the mediators of NPSLE. Others have emphasized the role of autoantibodies, such as anti-dsDNA, which have been shown to cross-react with neurotransmitter receptors and directly damage neurons. In this review, we present an integrative framework in which immune complexes deposited in the neurovasculature trigger local IFNα production in the brain. We discuss how complement activation amplifies inflammation by recruiting monocytes and promoting transcriptional shifts in glial cells toward reactive and neurotoxic states. Together, cellular and soluble immune effectors converge to disrupt neuronal function and drive the behavioral symptoms characteristic of NPSLE.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102608"},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656227","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}
{"title":"Friend or foe? — Janus Langerhans cells in skin immunity and promising clinical application","authors":"Mengjiao Chen , Shiyi Yan , Jun Li , Juan Tao","doi":"10.1016/j.coi.2025.102615","DOIUrl":"10.1016/j.coi.2025.102615","url":null,"abstract":"<div><div>Langerhans cells (LCs), the professional antigen-presenting cells in the epidermis, serve as the first line of defense in the skin's immune system. With advancements in detection technologies and the development of diverse animal models, LCs have been shown to exhibit heterogeneous origins, phenotypes, and functions, which are regulated in a context-dependent manner by various cytokines and transcription factors. This heterogeneity enables LCs to either promote or suppress immune responses depending on the microenvironment. As research advances in elucidating the regulatory mechanisms underlying LC phenotypes and functions across various pathological conditions, clinical studies targeting LCs are gradually progressing. This review summarizes commonly used experimental animal models in LC research, highlights the phenotypic diversity of LCs in various diseases, and discusses their dual roles in disease progression. With our understanding of LC heterogeneity deepening, we anticipate elucidating the characteristic of distinct LC subgroups, thereby establishing a solid foundation for LC-targeted precision immunotherapy.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102615"},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663567","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}
Armando Curto , Laura Cristoferi , Marco Carbone , Andrea Galli , Pietro Invernizzi
{"title":"Primary sclerosing cholangitis: what is new in the therapeutic landscape","authors":"Armando Curto , Laura Cristoferi , Marco Carbone , Andrea Galli , Pietro Invernizzi","doi":"10.1016/j.coi.2025.102613","DOIUrl":"10.1016/j.coi.2025.102613","url":null,"abstract":"<div><div>Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease affecting the intra- and extra-hepatic bile ducts, leading to progressive inflammation and fibrosis. Its pathogenesis is complex and involves genetic predisposition, environmental triggers, and their interaction through the gut–liver axis, mediated by the microbiota. To date, no approved therapies modify the natural history of PSC, and liver transplantation remains the only curative option.</div><div>This review provides an overview of current investigational therapies for PSC, emphasizing their mechanisms of action and relevance to the underlying disease biology. It also examines key challenges in therapeutic development, including the lack of validated surrogate end points, clinical heterogeneity, and the confounding effects of concomitant inflammatory bowel disease treatments factors that complicate trial design and interpretation.</div><div>Clarifying these aspects is essential to support the development of effective, targeted therapies for this complex and currently untreatable condition.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"96 ","pages":"Article 102613"},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656225","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}