Clinical immunology最新文献

{"title":"Novel pathogenic variants in CTLA4 and LRBA immune dysregulation: Reduced CTLA-4 expression with normal expression of co-stimulatory surface molecules","authors":"Samantha A.M. Tromp ,&nbsp;Ester M.M. van Leeuwen ,&nbsp;Machiel H. Jansen ,&nbsp;Arjan J. Kwakernaak ,&nbsp;Marije K. Bomers ,&nbsp;René E. Jonkers ,&nbsp;Resie M.L. van Spaendonk ,&nbsp;Taco W. Kuijpers ,&nbsp;Godelieve J. de Bree","doi":"10.1016/j.clim.2025.110565","DOIUrl":"10.1016/j.clim.2025.110565","url":null,"abstract":"<div><h3>Background</h3><div>Genetic variants in Cytotoxic T-Lymphocyte-associated protein 4 (<em>CTLA4</em>) and LPS responsive beige-like anchor protein (<em>LRBA</em>), involved in the same biological pathways, are implicated as monogenic causes of Common Variable Immunodeficiency Disorder (CVID). The pitfall in the recognition of CVID possibly related to CTLA-4 haploinsufficiency or LRBA deficiency is a clinical picture that is very heterogeneous. In the present study, we illustrate this challenge by means of clinical and immunological analysis of five patients with novel genetic variants in <em>CTLA4</em> and <em>LRBA</em>.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing (WES) was performed to identify genetic variants in the currently known immune genes in patients. Extensive immunophenotyping, lymphocyte proliferation assays and expression of CTLA-4 and a panel of 17 co-stimulatory molecules, both in rest and upon activation, were performed to gain insight into the impact of the genetic variants on B and T cell phenotype and function.</div></div><div><h3>Results</h3><div>A novel heterozygous variant in <em>CTLA4</em> (c.457 + 5G &gt; A) was identified in three members of a single family, all presenting with different clinical manifestations. In two additional patients, two genetic variants in <em>LRBA</em> (c.1771 T &gt; C; c.2450-3C &gt; A) were found, of which one is novel as well. The B cell phenotype was naïve with absence of non-switched and switched memory B cells in all patients except of the genetically affected elderly woman without any clinical manifestations. CD4 and CD8 T cell numbers and phenotype were normal. Differentiation of B cells into antibody secreting cells in vitro was reduced, especially in response to T cell-independent stimulation. The T cells showed impaired upregulation of CTLA-4 expression, which was most pronounced in CD4⁺CD25⁺FoxP3⁺ regulatory T cells, which helped to biologically support the genetic diagnosis.</div></div><div><h3>Conclusion</h3><div>The described novel genetic variants in <em>CTLA4</em> and <em>LRBA</em> show immunological impact and are therefore likely to underly an immune dysregulation syndrome with a highly variable clinical presentation. Apart from the immunophenotypic abnormal findings in activated T cells, the intrinsic B cell defect aids in the interpretation of novel genetic variants in these two genes in the context of a highly suspected clinical presentation.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110565"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616548","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":"A specific bone marrow cytokine pattern in de novo acute myeloid leukemia","authors":"Noémie Ravalet ,&nbsp;Hélène Guermouche ,&nbsp;Pierre Hirsch ,&nbsp;Frédéric Picou ,&nbsp;Vincent Flament ,&nbsp;Caroline Deswarte ,&nbsp;Amélie Foucault ,&nbsp;Jenny Beaud ,&nbsp;Emmanuelle Rault ,&nbsp;Emeline Saindoy ,&nbsp;Sébastien Lachot ,&nbsp;Mara Memoli ,&nbsp;Nawa Hachem ,&nbsp;Jean-Alain Martignoles ,&nbsp;Valérie Gissot ,&nbsp;Ludovic Suner ,&nbsp;Emmanuel Gyan ,&nbsp;Ollivier Legrand ,&nbsp;Olivier Hérault ,&nbsp;François Delhommeau","doi":"10.1016/j.clim.2025.110573","DOIUrl":"10.1016/j.clim.2025.110573","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic cancers. Cytokines play an important role in the regulation of normal and pathologic hematopoiesis. A pro-inflammatory state, described in hematopoietic malignancies, may participate in clonal selection. To identify recurrent cytokine patterns according to AML ontogenic subtypes, we quantified the concentration of 49 cytokines in the bone marrow (BM) plasma from 124 patients with AML or myelodysplastic syndrome (MDS), and from 94 healthy volunteers. We confirmed a pro-inflammatory profile in MDS and AML, with increased concentrations of CXCL8, CXCL10 and IL-6. Only a few cytokines varied when comparing AML to MDS. <em>De novo</em> AML subtypes carry a specific cytokine pattern dominated by the increase in CLEC11A concentrations and the decrease in FLT3 ligand concentrations. These cytokines could participate in clonal selection in this subtype of AML while being less critical in the other AMLs - <em>i.e.</em> secondary-like or <em>TP53-</em>mutated subtypes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110573"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712889","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":"A national survey of four decades of hereditary angioedema prophylaxis: Efficacy and safety of old and new drugs","authors":"Hanga Réka Horváth ,&nbsp;Beáta Visy ,&nbsp;Kinga Viktória Kőhalmi ,&nbsp;Zsuzsanna Balla ,&nbsp;Noémi Andrási ,&nbsp;Ibolya Czaller ,&nbsp;Zsuzsanna Zotter ,&nbsp;Henriette Farkas","doi":"10.1016/j.clim.2025.110542","DOIUrl":"10.1016/j.clim.2025.110542","url":null,"abstract":"<div><h3>Background</h3><div>Hereditary angioedema (HAE) imposes a significant burden on patients due to the unpredictability of attacks. Long-term prophylaxis (LTP) aims to prevent these episodes and improve quality of life. Over the past five decades, LTP options have evolved from non-specific treatments (fresh frozen plasma, attenuated androgens, antifibrinolytics) to more targeted therapies (intravenous or subcutaneous C1 inhibitor (C1INH), lanadelumab, berotralstat).</div></div><div><h3>Objective</h3><div>To assess the use, efficacy, and safety of various LTP therapies among Hungarian HAE patients.</div></div><div><h3>Methods</h3><div>Data from the Hungarian HAE Registry (1979–2023) were analysed, including LTP usage, attack rates, side effects, and laboratory parameters.</div></div><div><h3>Results</h3><div>Danazol and tranexamic acid use increased over the first 30 years but has declined in the last decade. Conversely, the use of modern LTP therapies and the proportion of patients relying solely on on-demand medication have significantly increased over the past decade. Danazol and tranexamic acid reduced attack rates in 60 % of patients without significant changes in the laboratory parameters at the lowest effective doses. Furthermore, 100 % of patients on subcutaneous C1INH, lanadelumab, and berotralstat experienced fewer attacks and improved quality of life compared to pre-treatment periods, with no serious side effects or significant laboratory abnormalities.</div></div><div><h3>Conclusion</h3><div>Modern prophylaxis usage is increasing among Hungarian HAE-C1INH patients, following the global trends. Both modern and traditional LTP options proved safe and effective in our patient population when used with appropriate monitoring.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110542"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293460","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":"Interleukin-5 is an adjunctive biomarker for engraftment syndrome in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation","authors":"Xing-Li Zhang ,&nbsp;Meng-Meng Pan ,&nbsp;Yaroslav Kaminskiy ,&nbsp;Shi-Wei Jin ,&nbsp;Jian-Qing Mi ,&nbsp;Wei-Ping Zhang ,&nbsp;Jie Xu","doi":"10.1016/j.clim.2025.110575","DOIUrl":"10.1016/j.clim.2025.110575","url":null,"abstract":"<div><div>Autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) can cause engraftment syndrome (ES), a clinical diagnosis without specific laboratory biomarkers. Herein, six cytokines commonly elevated during transplantation were chronologically detected during ASCT in 96 patients with newly diagnosed MM, 24.0 % of whom experienced ES. Among the molecules demonstrating remarkable peak levels, only IL-5 was able to differentiate ES from non-ES. IL-5 measured on day 12 emerged as an optimal indicator of ES, and its diagnostic value was enhanced when combined with the proportion of endogenous CD8⁺ T cells after engraftment and daratumumab-naive history. Notably, IL-5 levels on day 6 (IL-5 D6) served as the earliest predictor. 70.8 % of the patients could be predicted as having ES or non-ES via the IL-5 D6 cutoff value and daratumumab treatment history. It suggests that IL-5 can aid in estimating ES, and prior exposure to daratumumab may reduce the incidence of ES.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110575"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774794","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":"IKZF1: An important target for the treatment of autoimmune diseases","authors":"Siyuan Bu,&nbsp;Cong Ye,&nbsp;Shaozhe Cai,&nbsp;Lingli Dong","doi":"10.1016/j.clim.2025.110544","DOIUrl":"10.1016/j.clim.2025.110544","url":null,"abstract":"<div><div><em>IKZF1</em> is a member of the Ikaros transcription factor family. It is involved in the regulation of the development and function of a variety of immune cells. Mutations or aberrant expression of <em>IKZF1</em> are closely associated with the development of various immune-related diseases, including hematologic malignancies, solid tumors, and autoimmune diseases. In recent years, more and more studies have revealed the important role of <em>IKZF1</em> in regulating immune responses, maintaining immune tolerance, and inhibiting the overactivation of immune cells. What's more, <em>IKZF1</em> has been discovered to have a significant connection to the pathogenesis of autoimmune diseases. This review will summarize the role of <em>IKZF1</em> in autoimmune diseases and its potential clinical applications.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110544"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298556","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":"Comment on: “A national survey of four decades of hereditary angioedema prophylaxis” — The emerging role of Garadacimab","authors":"Haris Afridi,&nbsp;Kainat Afzal","doi":"10.1016/j.clim.2025.110547","DOIUrl":"10.1016/j.clim.2025.110547","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110547"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491694","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":"Oral microbiota in allergic diseases, and sublingual allergen immunotherapy","authors":"Umut Gazi ,&nbsp;Nerin Nadir Bahceciler","doi":"10.1016/j.clim.2025.110538","DOIUrl":"10.1016/j.clim.2025.110538","url":null,"abstract":"<div><div>Allergic diseases with their epidemic prevalence on the rise have been one of the major global health problems of the 21st century. The association of increased prevalence with lifestyle changes including increased urbanization, and hygiene practices highlighted the importance of host-microbiome interactions for maintaining immune homeostasis. In support, numerous studies demonstrated altered gut microbiome composition in allergic patients, and suggested dysbiosis as a possible cause of allergic diseases. Nevertheless, despite being the second largest microbiota in the human body, oral microbiota has not yet received the attention it deserves in the literature. With this review article, we aim to highlight its significance by summarizing the data obtained from studies evaluating oral microbiome composition in patients with allergic respiratory diseases. Additionally, their importance will be further elaborated by discussing the findings presented by animal and human studies investigating the possible effect of oral probiotic uptake to the clinical efficacy of sublingual allergen immunotherapy.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110538"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246729","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":"Differential control of mycobacterial growth ex vivo by COVID-19 patients is associated with CD8+ CD28+ T cells","authors":"Alba Llibre ,&nbsp;Henna Siddiqui ,&nbsp;Julie G. Burel ,&nbsp;Jamie Pillaye ,&nbsp;Charlotte Jones ,&nbsp;Harriet Hill ,&nbsp;Sian E. Faustini ,&nbsp;Ella F Windle ,&nbsp;Hanfa Karim ,&nbsp;Emma Sherry ,&nbsp;Christopher A. Green ,&nbsp;Martin Dedicoat ,&nbsp;Zania Stamataki ,&nbsp;Adam F. Cunningham ,&nbsp;Matthew K. O'Shea","doi":"10.1016/j.clim.2025.110539","DOIUrl":"10.1016/j.clim.2025.110539","url":null,"abstract":"<div><div>Diseases caused by SARS-CoV-2 and <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>) represent two public health emergencies. In severe presentations of disease, both pathogens may share a biological niche in the lower respiratory tract. There is significant potential for SARS-CoV-2 and <em>M.tb</em> infections to be co-present within individuals and modulate the respective outcomes of either infection. Here, we investigated how whole blood samples, as well as CD4+ and CD8+ T cells, from individuals hospitalised with acute COVID-19 disease respond to mycobacterial challenge. To do this, samples were assessed by ex vivo mycobacterial growth inhibition assays, immune cell phenotyping by mass cytometry, and whole blood cytokine responses to mycobacterial antigens assessed by flow cytometry. These studies identified a subgroup of COVID-19 patients whose blood had an enhanced capacity to inhibit mycobacterial growth. The ability to control mycobacterial growth was associated with the presence of a distinct non-<em>M.tb</em>-specific CD8+ CD28+ T cell population. This work improves our understanding of factors involved in mycobacterial control.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110539"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246728","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":"The role of immune cells glycolysis in neuroinflammation secondary to intracerebral hemorrhage","authors":"Baochun Luo ,&nbsp;Sifan Liu ,&nbsp;Lei Zheng ,&nbsp;Baiwen Zhang ,&nbsp;Yaxin Shang ,&nbsp;Tong Shang ,&nbsp;Jia Zheng ,&nbsp;Binglin Kuang ,&nbsp;Wei Zou","doi":"10.1016/j.clim.2025.110543","DOIUrl":"10.1016/j.clim.2025.110543","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, making the effective prevention and treatment of inflammatory secondary injury crucial. Recently, the role of immune cell metabolism in ICH has gained attention, particularly the regulatory mechanisms of glycolytic reprogramming in neuroinflammation. This review explores how glycolysis activation in peripheral immune cells (including neutrophils, macrophages, T cells, and natural killer cells), central immune cells (microglia), and other glial cells (including astrocytes and oligodendrocytes) involved in immune regulation influences the inflammatory response following ICH. We analyze the metabolic shifts in glycolysis within these immune cells, highlighting its dual role in neuroinflammation: glycolysis not only provides rapid energy to immune cells, which can either promote or inhibit inflammation, but lactate—a glycolysis byproduct—can modulate inflammatory damage by altering pH and immune cell function. Furthermore, we explore the therapeutic potential of targeting glycolysis in immune cells for neuroinflammation treatment. A deeper understanding of the glycolytic mechanism in ICH may facilitate the development of clinical therapeutic strategies targeting metabolism.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110543"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279142","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":"Scavenger receptors: An auspicious therapeutic target for autoimmune diseases","authors":"Yi-Kai Liu ,&nbsp;Meng Hao ,&nbsp;Fan Yang ,&nbsp;Ke-Xin Jing ,&nbsp;Shun Zhao ,&nbsp;Changhao Wu ,&nbsp;Hai-Feng Pan","doi":"10.1016/j.clim.2025.110546","DOIUrl":"10.1016/j.clim.2025.110546","url":null,"abstract":"<div><div>Scavenger receptors (SRs) belong to a large receptor family expressed on immune and non- immune cells. Initially, SRs are regarded as removers able to recognize and clear modified lipoproteins; However, it is now realized that they are pattern recognition receptors (PRRs) that identify damage-associated molecular pattern (DAMP) and pathogen-associated molecular patterns (PAMPs). The wide range of ligands that bind to SRs demonstrates their diverse functions, including pathogen clearance, lipid transport, cellular differentiation, and signaling pathway activation. Previous studies have revealed the significance of SRs in regulating innate immunity and adaptive immunity. Recently, a large body of evidence further indicates the involvement of SRs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D) and inflammatory bowel disease (IBD). In this comprehensive review, we will summarize molecular structure and immunological functions of different types of SRs, and discuss the recent insights into the involvement of SRs in the development and pathogenesis of autoimmune diseases and their clinical implications and therapeutic potential.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110546"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336007","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}