Clinical immunology最新文献

{"title":"Origin, functions, heterogeneity and associated diseases of B-1 cells","authors":"Weicheng Shen ,&nbsp;Shengyan Cui ,&nbsp;Yanqi Xia ,&nbsp;Luo Duan ,&nbsp;Yunpeng Dou ,&nbsp;Han Zhao ,&nbsp;Leixin Liu ,&nbsp;Wei Wang ,&nbsp;Ye Cui ,&nbsp;Yan Chen ,&nbsp;Jie Liu ,&nbsp;Zhe Lv ,&nbsp;Chris J. Corrigan ,&nbsp;Huihui Yuan ,&nbsp;Ying Sun","doi":"10.1016/j.clim.2025.110561","DOIUrl":"10.1016/j.clim.2025.110561","url":null,"abstract":"<div><div>B-1 cells are derived from a subpopulation of B lymphocytes which have a specific developmental process, unique phenotype and location, and distinct functions in comparison with conventional B-2 cells. The origin of B-1 cells is not completely clear, with two existing hypotheses concerning their lineage and differentiation pathways. B-1 cells are located principally in the peritoneal and pleural cavities, but are also distributed in secondary lymphoid tissues, at mucosal sites and in the blood and bone marrow. B-1 cells regulate immune responses and maintain homeostasis by secretion of natural antibodies (nAbs), and participate in the adaptive immune response through phagocytosis and presentation of antigens to T cells. B-1 cells are associated with many diseases including autoimmune, infectious and inflammatory diseases. This review focuses on the origin and biological functions of B-1 cells as well as their involvement in human disease, and discusses advances in the understanding of the heterogeneity of B-1 cells under specific pathophysiological features, as partly clarified by single-cell sequencing analysis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110561"},"PeriodicalIF":4.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616549","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":"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":"2025-07-10","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":"Analyses of peripheral blood NK cells in response to anti-PD-1 therapy in metastatic melanoma patients","authors":"Katarina Mirjačić Martinović ,&nbsp;Ana Vuletić ,&nbsp;Nevena Tišma Miletić ,&nbsp;Milica Nedeljković ,&nbsp;Suzana Matković ,&nbsp;Vladimir Jurišić","doi":"10.1016/j.clim.2025.110557","DOIUrl":"10.1016/j.clim.2025.110557","url":null,"abstract":"<div><div>Therapeutical blockade of programmed cell death protein 1 (PD-1) axis may enhance anti-tumor immunity and especially natural killer (NK) cells activity. In 32 BRAF wild type (wt) metastatic melanoma (MM) patients before and after every 12 weeks of therapy with PD-1 inhibitor, Pembrolizumab, we analyzed the percentage of T cell subsets, NK cells and CD14⁺HLA-DR⁻ monocytes, the expression of CD107a degranulation marker, activating NKG2D, NKp46, DNAM-1 and inhibitory CD158a receptors on NK cells by Flow cytometry, until one year or disease progression (DP). The patients with disease control (non-DP patients) had significant increase in lymphocyte count, percentage of NK cells, increased expression of CD107a, NKG2D, NKp46, but decreased CD158a on NK cells during Pembrolizumab therapy compared to pretherapy values. Patients with DP had increased neutrophil number, increased percentage of immunosuppressive CD14⁺HLA-DR⁻ monocytes, as well as increased CD158a expression on NK cells. In MM patients with disease control, contrary to DP patients blocking of PD-1 inhibitory molecule may increase NK cell cytotoxicity through enhancement of NK cell degranulation and activating receptor expression. Therefore, our findings show that NK cells and their receptors in MM patients may be potential biomarkers of response to Pembrolizumab.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110557"},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616547","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":"Measuring efficacy for myasthenia gravis treatments: A review of biomarkers used in clinical trials","authors":"Taylor Wesley,&nbsp;Callie Rose,&nbsp;Jessica Ding,&nbsp;Kirstin Parkin","doi":"10.1016/j.clim.2025.110560","DOIUrl":"10.1016/j.clim.2025.110560","url":null,"abstract":"<div><div>Myasthenia gravis is an autoimmune disease that impairs neuromuscular transmission through autoantibodies, most commonly targeting acetylcholine receptors (AChR). While clinical scores like the Quantitative Myasthenia Gravis Score (QMGS) and the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) are commonly used in trials, there is no gold standard biomarker for evaluating treatment efficacy. This scoping review aimed to identify which biomarkers are most frequently used in randomized controlled trials (RCTs) for non-surgical treatments of generalized myasthenia gravis. We searched five databases for English-language RCTs published before May 9, 2024. Of 6685 screened texts, 33 met inclusion criteria. A total of 33 distinct biomarkers were tracked across studies, with AChR antibodies, IgG, and IL-2 most frequently reported. Biomarkers were measured inconsistently and at varied intervals, limiting cross-study comparability. The lack of standardized biomarker use hinders the ability to assess treatment efficacy and perform meta-analyses. We recommend developing consensus guidelines to improve future trial quality.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110560"},"PeriodicalIF":4.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607708","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":"Tumor-associated neutrophils: a complex role in cancer","authors":"Xukang Gao ,&nbsp;Min Xu ,&nbsp;Hao Xiao ,&nbsp;Zeping Han ,&nbsp;Zhutao Wang ,&nbsp;Guoqiang Sun ,&nbsp;Dai Zhang ,&nbsp;Qiu Shuangjian ,&nbsp;Ning Ren ,&nbsp;Chenhao Zhou ,&nbsp;Yong Yi","doi":"10.1016/j.clim.2025.110558","DOIUrl":"10.1016/j.clim.2025.110558","url":null,"abstract":"<div><div>Neutrophils, constituting 50–70 % of circulating leukocytes, serve as first responders in innate immunity. In recent years, as research into the tumor immune microenvironment has intensified, the role of neutrophils in tumor has gained increasing attention. Studies have shown that neutrophils are involved in tumor growth, metastasis, angiogenesis, and immune regulation. However, because tumor-associated neutrophils (TANs) often exhibit dual-edged effects and significant heterogeneity, it remains challenging to determine whether they act as allies or adversaries. This review systematically summarizes the classification and functions of neutrophils in tumor. Additionally, the current challenges in tumor-associated neutrophils are discussed, aiming to provide new insights for the development of neutrophil-related immunotherapies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110558"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599641","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":"Animal models of IgG4-related disease","authors":"Manqi Tang ,&nbsp;Weicheng Shen ,&nbsp;Yanying Liu","doi":"10.1016/j.clim.2025.110559","DOIUrl":"10.1016/j.clim.2025.110559","url":null,"abstract":"<div><div>Immunoglobulin G4-Related Disease (IgG4-RD) is a recently characterized systemic autoimmune disorder marked by multiorgan inflammation and progressive fibrosis. It can affect nearly any organ and may lead to serious clinical consequences. Despite recent progress in developing animal models, therapeutic options for IgG4-RD remain limited, and the pathogenic mechanisms underlying immune dysregulation and fibrosis are still not fully understood. To support mechanistic and therapeutic research, both humanized and non-humanized animal models have been established in recent years. However, the unique biological features of the IgG4 molecule, together with genetic differences between humans and mice, present significant challenges to conventional mouse models. Although several models replicate certain features of IgG4-RD, none fully recapitulate the pathological hallmarks observed in patients. This review critically examines the strengths and limitations of current experimental models and outlines future directions for improving IgG4-RD model systems to better reflect human disease pathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110559"},"PeriodicalIF":4.5,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590537","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":"LSP1 deficiency increases IL-17-expressing T cells and accelerates primary Sjögren's syndrome","authors":"Jayhyun Kim ,&nbsp;Jung Gon Kim ,&nbsp;Yingjin Li ,&nbsp;Sungyong You ,&nbsp;Naeun Lee ,&nbsp;Wan-Uk Kim","doi":"10.1016/j.clim.2025.110548","DOIUrl":"10.1016/j.clim.2025.110548","url":null,"abstract":"<div><div>Lymphocyte-specific protein-1 (LSP1) is known to negatively regulate T cell migration in autoimmune diseases. However, its role in the development of T cell-dependent Sjögren's syndrome remains unknown. In this study, we found that LSP1 expression was decreased in T cells in salivary glands (SGs) of mice with experimental Sjögren's syndrome, accompanied by enhanced infiltration of leukocytes into SGs. Moreover, <em>Lsp1</em>^{<em>−/−</em>} mice had higher frequency of IL-17A-expressing T cells in cervical lymph nodes as well as increased severity in SGs than WT mice. Concurrently, LSP1 expression was reduced in human T cells of primary Sjögren's syndrome (pSS) patient. Particularly, pSS patients showed an increased Th17 cells, which inversely correlated with LSP1 expression. Taken together, these findings suggest that LSP1 deficiency promote Th17 cell development and exacerbation of pSS. LSP1 might be a potential therapeutic target to regulate Th17 response and to treat autoimmune diseases like pSS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110548"},"PeriodicalIF":4.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526684","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":"IL-33 regulates abnormally increased expression of ST2 in bone marrow follicular helper T cell in SLE with hematological abnormalities","authors":"Shaowei Pan ,&nbsp;Xiaoyun Xie ,&nbsp;Tong Li ,&nbsp;Shiyao Wu ,&nbsp;Ying Jiang ,&nbsp;Huali Zhang ,&nbsp;Xiaoli Zhang","doi":"10.1016/j.clim.2025.110550","DOIUrl":"10.1016/j.clim.2025.110550","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110550"},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505039","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":"Etiopathogenesis of Behçet's disease: A systematic literature review","authors":"Nabil Belfeki ,&nbsp;Nouha Ghriss ,&nbsp;Alexandre Le Joncour ,&nbsp;David Saadoun","doi":"10.1016/j.clim.2025.110549","DOIUrl":"10.1016/j.clim.2025.110549","url":null,"abstract":"<div><div>Behçet's disease (BD) is a chronic, multisystemic inflammatory vasculitis affecting veins and arteries. Its etiopathogenesis remains unclear but is thought to result from genetic predisposition combined with environmental triggers. Recent genome-wide association studies (GWAS) have linked various genetic polymorphisms (e.g., HLA*B51, ERAP1) to an increased risk of BD, with particular focus on cytokine-related gene variants. Infectious agents, such as <em>Streptococcus</em> species and herpes simplex virus, along with oral and intestinal dysbiosis and molecular mimicry, are key environmental triggers of innate immune inflammation, which is further amplified by adaptive immune responses. The innate immune system's primary cells, including neutrophils and NK cells, are upregulated, leading to an overproduction of proinflammatory cytokines. Additionally, an imbalance in T cell populations, characterized by a decrease in Tregs and expansion of Th1 and Th17 cells, contributes to disease pathogenesis. This review provides an overview of recent advances in understanding BD's etiopathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110549"},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505038","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":"2025-06-23","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}