Clinical immunology最新文献

{"title":"Microbiome alterations in primary Sjögren's syndrome: Regional dysbiosis and microbiome-targeted therapeutic strategies","authors":"Xujing Yuan ,&nbsp;Jun Wang ,&nbsp;Weiwei Wang ,&nbsp;You Song ,&nbsp;Jiajia Wu ,&nbsp;Rong Du","doi":"10.1016/j.clim.2025.110444","DOIUrl":"10.1016/j.clim.2025.110444","url":null,"abstract":"<div><div>Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by diverse clinical manifestations. While xerophthalmia and xerostomia are hallmark symptoms, the disease often involves multiple organ systems, including the kidneys, lungs, nervous system, and gastrointestinal tract, leading to systemic morbidity in severe cases. Despite extensive research, the precise pathogenesis of pSS remains unclear, likely involving infectious, hormonal, and genetic factors. Emerging evidence highlights the microbiome as a key contributor to autoimmune diseases, including pSS. Dysbiosis in the oral, ocular, gut, and genital microbiomes plays a critical role in disease onset, progression, and variability. This review summarizes current findings on microbiome alterations in pSS, emphasizing their role in pathogenesis and clinical features, and explores microbiome-targeted therapies. Understanding the role of the microbiome in pSS pathophysiology could advance disease management and inspire targeted therapeutic strategies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"273 ","pages":"Article 110444"},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413592","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":"Single-cell transcriptomics reveals the alteration of immune cell profile in peripheral blood of Henoch-Schonlein purpura","authors":"Wenhui Zhou ,&nbsp;Meiling Zheng ,&nbsp;Zhi Hu ,&nbsp;Bo Zhang ,&nbsp;Ming Zhao ,&nbsp;Qianjin Lu","doi":"10.1016/j.clim.2025.110443","DOIUrl":"10.1016/j.clim.2025.110443","url":null,"abstract":"<div><div>Henoch–Schönlein purpura (HSP) is an autoimmune vasculitis affecting multiple organs, and the understanding of circulating immune cell types and their states associated with disease subtypes of HSP remains incomplete. Here, we performed a comprehensive assessment of peripheral blood mononuclear cells of healthy donors and HSP patients, using both single-cell RNA sequencing and multiparameter flow cytometry. We revealed that HSP patients exhibited broad immune activation, evidenced by increased proportions of Effector memory CD8+ T, CD14+ monocytes, Tfh, Th2, Th17, Plasma, and B cells and decreased proportions of Naïve CD4+ T, Treg, Th1, and NK cells. Notably, we identified that cytotoxic effector T cell subsets were enriched in skin and renal type of HSP, whereas Plasma, B, and Tfh cells were expanded in joint and abdominal type of HSP. In conclusion, our findings highlight the dynamic nature of immune responses throughout the progression of HSP with different clinical manifestations.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110443"},"PeriodicalIF":4.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A distinct immunophenotype in children carrying the Blautia enterotype: The Generation R study","authors":"Christina Grosserichter-Wagener ,&nbsp;Kirsten I.M. Looman ,&nbsp;Sanne A. Beth ,&nbsp;Djawad Radjabzadeh ,&nbsp;Paul A. Gill ,&nbsp;Kyra N. Smit ,&nbsp;Liesbeth Duijts ,&nbsp;Jessica C. Kiefte-de Jong ,&nbsp;Robert Kraaij ,&nbsp;Henriëtte A. Moll ,&nbsp;Menno C. van Zelm","doi":"10.1016/j.clim.2025.110426","DOIUrl":"10.1016/j.clim.2025.110426","url":null,"abstract":"<div><h3>Objective</h3><div>Studies in mouse models and human adults have shown that the intestinal microbiota composition can affect peripheral immune cells. We here examined whether the gut microbiota compositions affect B and T-cell subsets in children.</div></div><div><h3>Methods</h3><div>The intestinal microbiota was characterized from stool samples of 344 10-year-old children from the Generation R Study by performing 16S rRNA sequencing. Bray-Curtis dissimilarity was used to cluster distinct microbiome compositions (enterotypes). B-cell and T-cell phenotypes were defined by 11-color-flow cytometry. Linear regression models with adjustment for lifestyle and child characteristics were performed to determine associations between enterotypes and immune cell numbers.</div></div><div><h3>Results</h3><div>Three enterotypes with distinct microbiota composition were found, characterized by high abundance of <em>Prevotella</em>, <em>Bacteroides</em> and <em>Blautia.</em> Children with the <em>Blautia</em> enterotype had decreased numbers of plasmablasts, CD4⁺ central memory (Tcm) T cells and follicular T-helper cells (Tfh), while Th22 cells and CD4⁺ effector memory (Tem) T cells, CD27⁻IgA⁺ memory B cells and CD27⁻IgE⁺ memory B cells, were increased in these children. In addition, in children with the <em>Blautia</em> enterotype CD4⁺ Tcm cell numbers expressing the β7 integrin, which can pair with α4 to mediate intestinal homing were also lower, while CD4⁺β7⁺ Tem cell numbers were higher than in the other enterotypes.</div></div><div><h3>Conclusion</h3><div>The <em>Blautia</em> enterotype showed features beneficial for human health. Enterotypes were associated with differences in memory B- and T-cell compartments. This study is unique in the detailed analysis of the B and T-cell compartment and the intestinal microbiome in a large generic pediatric cohort, enabling correction for child and maternal covariates. These outcomes could guide further studies about the impact of intestinal microbiome intervention, for instance through diet and microbiota metabolites such as short chain fatty acid production.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110426"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical advancements in mRNA vaccines against viral infections","authors":"Munazza Fatima ,&nbsp;Pil-Gu Park ,&nbsp;Kee-Jong Hong","doi":"10.1016/j.clim.2024.110424","DOIUrl":"10.1016/j.clim.2024.110424","url":null,"abstract":"<div><div>Over the last decade, mRNA vaccines development has shown significant advancement, particularly during the COVID-19 pandemic. This comprehensive review examines the efficacy of pivotal vaccines against emerging COVID-19 variants and strategies for enhancing vaccine effectiveness. It also explores the versatility of mRNA technology in addressing other infectious diseases such as influenza, respiratory syncytial virus, HIV, cytomegalovirus, Ebola, Zika, Rabies, and Nipah viruses. The analysis includes safety and clinical progress of mRNA vaccines and evaluates their potential in combination vaccine strategies. Additionally, it addresses challenges related to delivery and scalability while highlighting opportunities for future advancements in the field. Recent advances in mRNA optimization, biomaterial-based delivery and thermostable designs offer promising solutions. It is essential to gain insights into the evolving landscape of mRNA vaccine technology to maximize its vital role in addressing diverse viral threats, advancing vaccinology and enhancing public health preparedness for future pandemic.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110424"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902780","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":"Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease","authors":"Amin Alirezaylavasani ,&nbsp;Ingrid Marie Egner ,&nbsp;Børresdatter Dahl ,&nbsp;Adity Chopra ,&nbsp;Taissa de Matos Kasahara ,&nbsp;Guro Løvik Goll ,&nbsp;Jørgen Jahnsen ,&nbsp;Gunnveig Grødeland ,&nbsp;John Torgils Vaage ,&nbsp;Fridtjof Lund-Johansen ,&nbsp;Jan Cato Holter ,&nbsp;Bente Halvorsen ,&nbsp;Kristin Kaasen Jørgensen ,&nbsp;Ludvig A. Munthe ,&nbsp;Hassen Kared","doi":"10.1016/j.clim.2024.110404","DOIUrl":"10.1016/j.clim.2024.110404","url":null,"abstract":"<div><div>Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population.</div><div>While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110404"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NADPH oxidase expression profile and PBMC immunophenotypic changes in anti-TNF-treated rheumatoid arthritis patients","authors":"Tomasz Wysocki,&nbsp;Anna Wajda,&nbsp;Tomasz Kmiołek,&nbsp;Jakub Wroński,&nbsp;Magdalena Roszkowska,&nbsp;Marzena Olesińska,&nbsp;Agnieszka Paradowska-Gorycka","doi":"10.1016/j.clim.2024.110414","DOIUrl":"10.1016/j.clim.2024.110414","url":null,"abstract":"<div><div>The aim of this research was to prospectively evaluate the impact of NOX2 gene expression profile (including <em>NCF1</em>, <em>NCF2</em> and <em>NCF4</em> genes) in peripheral blood mononuclear cells (PBMCs) on immune signatures, clinical characteristics and responsiveness to anti-TNF treatment in RA patients. Blood specimens were collected from 31 rheumatoid arthritis (RA) patients and 25 healthy controls, and 16 RA patients were followed at two timepoints during anti-TNF treatment. mRNA expression levels of selected genes and immunoregulatory cytokines concentrations were determined. We observed the significant upregulation of <em>NCF4</em> and <em>CD14</em> expression in RA group. The mRNA levels of <em>NCF1</em> and <em>CD14</em> positively correlated both in groups of RA patients and healthy controls. NOX2 gene expression profile was not associated with anti-TNF responsiveness, nor with RA clinical features. TNFα inhibition has not influenced NOX2 expression either. Notably, this study indicate the novel links between expression levels of NCF1 and monocyte differentiation antigen CD14.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110414"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791052","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":"Circulatory age-associated B cells: Their distinct transcriptomic characteristics and clinical significance in drug-naïve patients with rheumatoid arthritis","authors":"Jung Gon Kim ,&nbsp;Mingyo Kim ,&nbsp;Bong-Ki Hong ,&nbsp;Yong-Ho Choe ,&nbsp;Ju-Ryoung Kim ,&nbsp;Naeun Lee ,&nbsp;Sungyong You ,&nbsp;Sang-Il Lee ,&nbsp;Wan-Uk Kim","doi":"10.1016/j.clim.2024.110425","DOIUrl":"10.1016/j.clim.2024.110425","url":null,"abstract":"<div><div>Age-associated B cells (ABCs) have been implicated in the pathogenesis of autoimmune diseases. However, the global gene expression and clinical significance of circulatory ABCs in rheumatoid arthritis (RA) remain poorly understood. Here, single-cell RNA sequencing identified nine B cell subsets in peripheral blood of RA patients, including ABCs. Increased phagocytosis and antigen presentation were functionally enriched by the genes expressed differentially in ABCs. Network analysis and in vitro experiments demonstrated SYK as a key regulator defining the myeloid-like phenotypes in ABCs. Flow cytometry showed that the proportion of ABCs correlated with RA activity and serum tumor necrosis factor-alpha level. Notably, ABCs above a cutoff threshold specifically distinguished RA from healthy controls and indicated higher disease activity. This study highlights the myeloid characteristics of circulatory ABCs regulated by SYK in RA. Increased ABCs may reflect disease activity and could serve as a potential biomarker in RA.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110425"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920938","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":"Overfeeding and overweight rapidly reprogram inflammatory signaling","authors":"Megan Elkins ,&nbsp;Merle Horrelt ,&nbsp;Brian Woods ,&nbsp;Samira Lawton ,&nbsp;Toshiro K. Ohsumi ,&nbsp;Amy Fleischman ,&nbsp;Verena Taudte ,&nbsp;Janet Chou","doi":"10.1016/j.clim.2025.110428","DOIUrl":"10.1016/j.clim.2025.110428","url":null,"abstract":"<div><div>Epidemiologic studies have shown a continuous increase in mortality risk associated with overweight, thus highlighting the health risks beginning before the onset of obesity. However, early changes in inflammatory signaling induced by an obesogenic diet remain largely unknown since studies of obesity typically utilize models induced by months of continuous exposure to a high-fat diet. Here, we investigated how short-term overfeeding remodels inflammatory signaling. We developed and characterized a mouse model of overweight induced by seven days of the Western diet enriched in saturated fats and sucrose, compared to the standard, low-fat laboratory diet or a long-term Western diet for 22 weeks. The short-term Western diet caused a median weight gain of 6 %, while the long-term Western diet increased weight by 92 %. Circulating levels of cholesterol, triglycerides, insulin, and leptin were increased by both diets, but only the long-term Western diet caused transaminitis and significant hepatic steatosis. Both models reduced the alpha and beta diversity of the microbiome. Tryptophan metabolism was perturbed by both models; the long-term Western diet also affected histidine and vitamin B6 metabolism. The short-term and long-term Western diets increased expression of TLR4 on peritoneal immune cells and TLR4-driven plasma levels of proinflammatory cytokines comparably, showing one week of the Western diet was sufficient for inducing inflammation typical of chronic obesity. These findings highlight the importance of diet not only in preclinical studies, but also in the clinical care of individuals with inflammatory disorders.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110428"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945810","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":"Resident synovial macrophages in synovial fluid: Implications for immunoregulation","authors":"Karen I. Cyndari ,&nbsp;Breanna M. Scorza ,&nbsp;Zeb R. Zacharias ,&nbsp;Danielle Pessôa-Pereira ,&nbsp;Leela Strand ,&nbsp;Kurayi Mahachi ,&nbsp;Juan Marcos Oviedo ,&nbsp;Lisa Gibbs ,&nbsp;Katherine L. Butler ,&nbsp;Graham Ausdal ,&nbsp;Dylan Hendricks ,&nbsp;Rika Yahashiri ,&nbsp;Jacob M. Elkins ,&nbsp;Trevor Gulbrandsen ,&nbsp;Andrew R. Peterson ,&nbsp;Michael C. Willey ,&nbsp;Keke C. Fairfax ,&nbsp;Christine A. Petersen","doi":"10.1016/j.clim.2024.110422","DOIUrl":"10.1016/j.clim.2024.110422","url":null,"abstract":"<div><div>Resident synovial macrophages (RSMs) are anti-inflammatory, self-renewing macrophages that provide physical immune sequestration of the joint space from the peripheral immune system. Increased permeability of this structure is associated with peripheral immune cells in the synovial fluid (SF). Direct measures of synovial barrier integrity are possible with tissue histology, but after barrier breakdown, if these cells perpetuate or initiate chronic inflammation in SF remains unknown. We sought to identify RSM in human SF as an indirect measure of synovial barrier integrity. To validate findings, we created a novel <em>ex vivo</em> explant model using human synovium. scRNA-seq revealed these SF RSMs upregulated pro-fibrotic and pro-osteoclastic pathways in inflammatory arthritis, but not septic arthritis. Increased frequencies of RSMs in SF was associated with increased sRANKL regardless of underlying pathology. These findings suggest the frequency of RSMs in SF may correlate with synovial barrier damage and in turn, potential damage to joint structures.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110422"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary and systemic effects of inhaled crystalline silica in the HOCl-induced mouse model of systemic sclerosis: An experimental model of Erasmus syndrome.","authors":"Laura Morin ,&nbsp;François Zimmermann ,&nbsp;Marie Lelong ,&nbsp;Juliette Ferrant ,&nbsp;Patrice Hemon ,&nbsp;Salomé Patry ,&nbsp;Erwan Le Tallec ,&nbsp;Francine Uwambayinema ,&nbsp;Yousof Yakoub ,&nbsp;Erwan Dumontet ,&nbsp;François Huaux ,&nbsp;Alain Lescoat ,&nbsp;Valérie Lecureur","doi":"10.1016/j.clim.2024.110423","DOIUrl":"10.1016/j.clim.2024.110423","url":null,"abstract":"<div><div>Occupational exposure to crystalline silica is etiologically linked to an increased incidence of systemic sclerosis (SSc), also called Erasmus syndrome. The underlying mechanisms of silica-related SSc are still poorly understood. We demonstrated that early and repeated silica exposure contribute to the severity of SSc symptoms in the hypochloric acid (HOCl)-induced SSc mouse model. Analyses of lung samples from silica-exposed HOCl mice revealed a slightly aggravation of fibrosis and an exacerbation of inflammation, notably an additionally overexpression of NLRP3 inflammasome genes and a recruitment of classical monocytes, macrophages, dendritic cells and neutrophils. Silica exposure showed systemic effects in SSc mouse model with an elevated circulating classical monocyte counts and an overexpression of inflammatory genes in the skin. Silica-exposed SSc patients also had more severe skin disease than unexposed patients. Overall, we provide new insights on immune cell populations and related pathways in early pathogenic mechanisms contributing to HOCl-induced and silica-related SSc.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110423"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}