Clinical & Translational Immunology最新文献

{"title":"Adaptive immune response to the autoantigen LL-37 differentiates atherosclerotic cardiovascular disease phenotypes","authors":"Paul C. Dimayuga,&nbsp;Kuang-Yuh Chyu,&nbsp;Jianchang Zhou,&nbsp;Xiaoning Zhao,&nbsp;Janet Wei,&nbsp;Bojan Cercek,&nbsp;Prediman K. Shah","doi":"10.1002/cti2.70083","DOIUrl":"https://doi.org/10.1002/cti2.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Atherosclerosis is the common underlying pathology in atherosclerotic cardiovascular disease (ASCVD) phenotypes of myocardial infarction (MI), stroke or peripheral artery disease (PAD). Single immune cell profiling of atherosclerotic plaques demonstrates a site-specific immune profile associated with the ASCVD phenotype, and LL-37 is a reported autoantigen in atherosclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate whether the immune response to LL-37 would be common among different ASCVD phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells (PBMCs) and plasma were collected from stable ASCVD patients enrolled within 12 months after MI or stroke or diagnosed with PAD. A subgroup of post-acute patients provided PBMCs at follow-up (14.7 ± 3.6 months). T-cell response to LL-37 was profiled using activation-induced markers. LL-37 IgG, immune complex (IC) levels and subclass were evaluated with ELISA. LDL is a reported binding partner of LL-37 in plasma. Therefore, cross-reactivity of LL-37 IgG-ICs with native LL-37 or LL-37 complexed with LDL (LL-37_LDL) was assessed using immune depletion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LL-37 provokes increased CD4⁺CD25⁺CD134⁺ T-cell response in stable post-MI patients whereas CD8⁺CD25⁺CD69⁺ T cells were reduced in PAD. CD4⁺ T-cell response to LL-37 in post-MI patients persisted at follow-up with increased CD4⁺CD25⁺CD69⁺FoxP3⁺ T regulatory cells while post-stroke patients had increased CD8⁺CD134⁺ T cells. LL-37 IgG-ICs were significantly increased in ASCVD patients with IgG3 subclass reduced in post-MI compared to post-stroke. Immune-depletion showed cross-reactivity of LL-37 IgG-ICs with both native LDL and LL-37_LDL only in post-MI plasma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LL-37 antigen specific profiling of immune response may differentiate various ASCVD phenotypes and provide mechanistic insight in pathophysiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, biological and cytometric characteristics of two patients with a homozygous A91V PRF1 mutation","authors":"Nicolas Perrard,&nbsp;Claire Poggi,&nbsp;Sébastien Sanges,&nbsp;Bruno Lemarchant,&nbsp;Wadih Abou Chahlah,&nbsp;Louis Terriou,&nbsp;Stéphanie Delangue,&nbsp;Jacques Trauet,&nbsp;Myriam Labalette,&nbsp;Eric Hachulla,&nbsp;Despina Moshous,&nbsp;Guillaume Lefevre,&nbsp;David Launay","doi":"10.1002/cti2.70081","DOIUrl":"https://doi.org/10.1002/cti2.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Inborn errors of immunity are rare genetic disorders that cause dysfunction of the immune system. Among these, familial haemophagocytic lymphohistiocytosis (FHL) involves defects in the perforin/granzyme pathway, which is essential for regulating immune responses. These conditions predispose individuals to haemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome. FHL has traditionally been described in paediatric patients with a fatal outcome in the absence of early haematopoietic stem cell transplantation. However, some patients harbouring missense mutations may present with atypical or late-onset symptoms, for which management remains unstandardised. Among these reported variants, the pathogenicity of the A91V <i>PRF1</i> mutation remains the most controversial in the literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We report clinical, biological and cytometric characteristics of two patients with a homozygous <i>PRF1</i> A91V mutation who developed clinical features consistent with FHL2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>We discuss the latest 2024 classifications to better characterise this group of disorders and their underlying genetic basis, with particular emphasis on atypical presentations and the A91V mutation, which may pose diagnostic and therapeutic challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A91V <i>PRF1</i> variant appears to represent a risk factor for the development of atypical FHL manifestations under divers triggers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147614895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the immune landscape and microenvironmental architecture of IgA nephropathy using single-cell imaging mass cytometry","authors":"Xing Chen,&nbsp;Long Liu,&nbsp;Lijing Yao,&nbsp;Jianxin Shen,&nbsp;Hengyuan Zhang,&nbsp;Leping Shao,&nbsp;Xingxing Yu,&nbsp;Zhijuan Lin,&nbsp;Lu Zhang","doi":"10.1002/cti2.70088","DOIUrl":"https://doi.org/10.1002/cti2.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The heterogeneity in the pathology of IgA nephropathy (IgAN) represents a significant gap in current research, emphasising the need for individualised treatment strategies. The role of the glomerular microenvironment in driving IgAN heterogeneity remains largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study employed Imaging Mass Cytometry (IMC) to analyse 34 primary IgAN renal biopsies. A panel of 35 protein markers was used to identify and characterise 17 cell clusters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Immune cells composed of 9.64% of the glomerular cell population, with macrophages being the predominant subset. While there was no significant difference in the overall percentage of immune cells across glomeruli exhibiting different pathological features, including mesangial proliferation, global sclerosis, segmental sclerosis and crescents, the infiltration pattern of these cells was distinct. Neighbourhood analysis revealed that the interaction mode of M1-like macrophages varied significantly among these four glomerular pathology types. Severe IgAN (Lee grades IV–V) was associated with a lower glomerular M1/M2-like macrophage infiltration ratio compared to mild IgAN (Lee grade III). The M1/M2-like macrophage ratio positively correlated with the estimated glomerular filtration rate (eGFR), while M2-like macrophages correlated with proteinuria, and T cells were associated with haematuria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study findings underscore that glomerular immune cell subtypes and their interaction patterns critically influence pathological and clinical outcomes, suggesting a new potential direction for molecular therapeutic strategies targeting the IgAN microenvironment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147614853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of single-cell and bulk transcriptomics reveals the association of manganese metabolism-related genes with prognosis and immune infiltration in lung adenocarcinoma","authors":"Hongliang Li,&nbsp;Shuzhen Wei,&nbsp;Wei Li,&nbsp;Junxia Sun,&nbsp;Yi Wang","doi":"10.1002/cti2.70085","DOIUrl":"https://doi.org/10.1002/cti2.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) is associated with a poor prognosis. Manganese metabolism plays a critical role in antitumor immunity. The prognostic significance of manganese metabolism–related genes (MRGs) in LUAD remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing and TCGA transcriptomic data were integrated to identify expressed MRGs. Cell subpopulations were defined using AUCell scoring. A prognostic signature was constructed using univariate Cox regression, LASSO regression and multivariate Cox analysis. A nomogram incorporating the manganese metabolism–related risk score (MRS) and clinical variables was developed, and predictive performance was evaluated using receiver operating characteristic curves. Immune infiltration patterns and drug sensitivity were further analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A robust prognostic model based on nine genes, including KLRF1, demonstrated strong predictive performance. Patients in the high-MRS group exhibited increased M1 macrophage infiltration and shorter overall survival, whereas the low-MRS group was characterised by enrichment of resting dendritic cells. Drug sensitivity analyses suggested that JQ1 and Vorinostat may be more effective in low-MRS patients, while Pevonedistat and LCL161 may be preferable for high-MRS patients. <i>In vitro</i> experiments confirmed that high PTMA expression promoted malignant phenotypes in LUAD cells, and that combined JQ1 treatment and PTMA knockdown exerted synergistic antitumor effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We established and validated a prognostic signature based on nine MRGs. The synergistic antitumor effects of JQ1 and PTMA suppression were verified. This model provides a novel biomarker framework and therapeutic guidance for prognostic assessment and personalised treatment in LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147614827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza virus infection drives upregulation of CD84 across a broad range of immune cells","authors":"Xiaoxiao Jia,&nbsp;Isabelle JH Foo,&nbsp;Hayley A McQuilten,&nbsp;Jeremy Chase Crawford,&nbsp;Aira F Cabug,&nbsp;Deborah Gebregzabher,&nbsp;Janet Chou,&nbsp;Robert C Mettelman,&nbsp;Tanya Novak,&nbsp;Lee-Ann Van de Velde,&nbsp;Ryan S Thwaites,&nbsp;Adrienne G Randolph,&nbsp;Paul G Thomas,&nbsp;Jianqing Xu,&nbsp;Zhongfang Wang,&nbsp;Katherine Kedzierska,&nbsp;Lukasz Kedzierski,&nbsp;Brendon Y Chua","doi":"10.1002/cti2.70087","DOIUrl":"10.1002/cti2.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our previous study in hospitalised patients infected with avian A(H7N9) influenza virus identified <i>CD84</i> amongst several genes associated with recovery. Yet, the correlation between CD84 and respiratory viral infection outcomes is far from established. We aimed to define CD84 dynamics in patient cohorts of respiratory disease and immune cell populations in influenza virus-infected mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Expression dynamics of <i>CD84</i> and association with previously identified correlates of severe and fatal respiratory disease outcomes, <i>OLAH</i> and <i>IL18R1</i>, were analysed in A(H7N9) and COVID-19 patient cohorts across disease severities. Using mouse models of influenza virus infection, CD84 expression on immune cell subsets was analysed over the course of infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated <i>CD84</i> levels in recovered A(H7N9) patients were accompanied by increased expression of genes for CD84-associated adaptor proteins and other SLAM receptor family members. In these patients, high <i>CD84</i> expression persisted until discharge, while remaining low throughout the disease in patients that succumbed. We found inverse correlations between <i>CD84</i> with <i>OLAH</i> and <i>IL18R1</i> levels in our A(H7N9) cohort, and in hospitalised COVID-19 patients across respiratory disease severities. In influenza virus-infected mice, CD84 was upregulated on a broad range of immune cell populations, particularly on activated and influenza virus-specific T-cell populations and correlated with less disease severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings revealed the link between high CD84 expression in humans and recovery from respiratory viral infections. In mice, CD84 expression increased across a broad range of immune cell populations, with CD84 expression on activated T-cell populations correlating with less severe disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated humoral and inflammatory signatures predict outcomes in severe COVID-19: a 14-day longitudinal analysis","authors":"Hiochelson Najibe Santos Ibiapina,&nbsp;Fabio Magalhães-Gama,&nbsp;Juliana Costa Ferreira Neves,&nbsp;Fabíola Silva Alves-Hana,&nbsp;Ismael Artur Costa-Rocha,&nbsp;Alice Aparecida Lourenço,&nbsp;Ágata Lopes Ribeiro,&nbsp;Geovane Marques Ferreira,&nbsp;Thais Fernanda Campos Fraga-Silva,&nbsp;Adriana Alves Oliveira Paim,&nbsp;Daisymara Priscila Almeida Marques,&nbsp;Joaquim Pedro Brito-de-Sousa,&nbsp;Ana Carolina Campi-Azevedo,&nbsp;Vanessa Peruhype-Magalhães,&nbsp;Márcio Sobreira Silva Araújo,&nbsp;Andréa Teixeira-Carvalho,&nbsp;Vânia Luiza Deperon Bonato,&nbsp;Christiane Becari,&nbsp;Mayra Gonçalves Manegueti,&nbsp;Marcelo Cordeiro-Santos,&nbsp;Maria Auxiliadora-Martins,&nbsp;Jordana Grazziela Coelho-dos-Reis,&nbsp;Olindo Assis Martins-Filho,&nbsp;Allyson Guimarães Costa","doi":"10.1002/cti2.70082","DOIUrl":"10.1002/cti2.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Severe COVID-19 is marked by profound immune dysregulation, yet the interplay between humoral and inflammatory responses that determines clinical outcomes in critically ill patients remains incompletely understood. We evaluated longitudinal antibody and soluble immune mediator profiles to identify prognostic signatures associated with survival in severe COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective longitudinal study, peripheral blood samples were collected from 30 unvaccinated adults with severe COVID-19 admitted to the intensive care unit (ICU) and 30 healthy controls. Serum concentrations of SARS-CoV-2–specific IgM, IgG and IgA antibodies (S1, RBD and N) and 27 cytokines, chemokines and growth factors were quantified at ICU admission (D0), Day 7 (D7) and Day 14 (D14) using Luminex multiplex assays. Patients were classified according to clinical outcome: discharge (DIS) or death (DEA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DIS and DEA patients exhibited distinct immunological trajectories. DEA patients showed early elevations of IgM anti-N and IgM anti-RBD at D0, accompanied by increased IFN-γ. At D7, persistently elevated TNF-α and FGF-basic differentiated nonsurvivors, while by D14, higher levels of CXCL8, CCL4, CXCL10 and G-CSF were strongly associated with mortality. In contrast, DIS patients exhibited more coordinated immune regulation, including sustained IL-13 production and higher IgA anti-S1 and IgA anti-RBD levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Integrated humoral and inflammatory signatures, particularly early IgM anti-N/anti-RBD responses and sequential increases in IFN-γ, TNF-α, FGF-basic, CXCL8, CCL4, CXCL10 and G-CSF, highlight immune signatures associated with poor outcomes. IL-13 and coordinated antibody interactions may reflect protective immune pathways. These findings highlight the prognostic value of multidimensional immune monitoring in severe COVID-19.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut metabolites identified in cerebrospinal fluid of genetic interferonopathy support gut–brain endothelial dysfunction","authors":"Russell C Dale,&nbsp;Madysen Elbourne,&nbsp;Markus J Hofer,&nbsp;Shrujna Patel,&nbsp;Shekeeb Mohammad,&nbsp;Velda X Han,&nbsp;Josephine Yu,&nbsp;Shanlin Fu,&nbsp;Arlene D'Silva,&nbsp;Michelle A Farrar,&nbsp;Sushil Bandodkar,&nbsp;Jingya J Yan","doi":"10.1002/cti2.70074","DOIUrl":"10.1002/cti2.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Aicardi–Goutières syndrome (AGS) is a rare genetic interferonopathy because of aberrant DNA or RNA metabolism with secondary host anti-viral (interferon) activation. This metabolomics study aimed to improve the biological understanding of AGS and explore potential biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed untargeted cerebrospinal fluid (CSF) metabolomics using a UPLC-Q-Exactive-HFx Mass Spectrometry of 10 genetically confirmed AGS patients (8 males, mean 4.8 years, range 0.2–16.5) and age-sex matched controls. Metabolites were then quantified and validated using UHPLC-QqQ-MS/MS in CSF and serum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified expected elevated inflammatory metabolites (neopterin and kynurenine) and unexpected elevated gut microbe metabolites in CSF samples: Indole, p-Cresol, γ-Butyrobetaine and N-Butyryl-L-homoserine lactone (all <i>P</i>_FDR &lt; 0.05). Using a targeted assay, we confirmed elevation of these metabolites in CSF, and also in the serum of patients with AGS (all <i>P</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest gut microbe metabolite leakage traversing the gut–blood–brain barrier in AGS, potentially because of endothelial dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of B-cell reconstitution on mRNA vaccine responses in allogeneic stem cell transplant recipients","authors":"Fredrika Hellgren,&nbsp;Rodrigo Arcoverde Cerveira,&nbsp;Gustaf Lindgren,&nbsp;Puran Chen,&nbsp;Klara Lenart,&nbsp;Sebastian Ols,&nbsp;Alberto Cagigi,&nbsp;Davide Valentini,&nbsp;Mireia Rocavert Barranco,&nbsp;Evangelin Shaloom Vitus,&nbsp;Martin Corcoran,&nbsp;Yong-Dae Gwon,&nbsp;Mattias NE Forsell,&nbsp;Magnus Evander,&nbsp;COVAXID Study Group,&nbsp;Peter Bergman,&nbsp;Marcus Buggert,&nbsp;Hans-Gustaf Ljunggren,&nbsp;Soo Aleman,&nbsp;Gunilla B Karlsson Hedestam,&nbsp;Andreas Björklund,&nbsp;Anna Nordlander,&nbsp;Per Ljungman,&nbsp;Stephan Mielke,&nbsp;Karin Loré","doi":"10.1002/cti2.70077","DOIUrl":"https://doi.org/10.1002/cti2.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Vaccine responses in haematopoietic stem cell transplant (alloHCT) recipients vary, with different degrees of B-cell reconstitution likely playing a key role. However, mechanistic understanding of the B-cell receptor (BCR) repertoire and its functional impact post-alloHCT remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Within the scope of a mRNA SARS-CoV-2 vaccine phase IV clinical trial in alloHCT recipients (<i>n</i> = 77), we have measured antibody titers and avidity, and performed B-cell immunophenotyping and B-cell receptor repertoire sequencing in sub-populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AlloHCT patients receiving prime-boost mRNA vaccination within 12 months post-transplant exhibited lower vaccine-specific antibody levels and memory B-cell frequencies than vaccinated healthy controls. Responses were comparable to healthy controls in patients vaccinated later than 12 months post transplant. BCR repertoire sequencing showed reduced somatic hypermutation (SHM) levels in bulk IgG+ B cells from alloHCT patients. Although some alloHCT patients showed exceptional expansion of a few IgG clones of unknown specificity, their overall B-cell repertoires remained polyclonal. Vaccine-specific B-cell clonotypes detected in patients responding to vaccination showed similar proportional expansion and SHM as in controls. The level of immature CD24hiCD38hi transitional B cells pre-vaccination was negatively correlated to the vaccine response, and can be used as a predictor of antibody titres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data indicate that mRNA vaccination can stimulate expansion of vaccine-specific B cells to affinity mature in many alloHCT recipients, though restricted by the presence of immature B-cell populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD56bright NK cells are negatively associated with antibody response to vaccination in people with multiple sclerosis on B-cell-depleting therapy","authors":"Griffith B Perkins,&nbsp;Christopher M Hope,&nbsp;Cheng Sheng Chai,&nbsp;Matthew J Tunbridge,&nbsp;Sebastian Sterling,&nbsp;Kevin Webb,&nbsp;Joey Yap,&nbsp;Arthur Eng Lip Yeow,&nbsp;Makutiro G Masavuli,&nbsp;Jacqueline Scaffidi,&nbsp;James D Zuiani,&nbsp;Anouschka Akerman,&nbsp;Anupriya Aggarwal,&nbsp;Vanessa Milogiannakis,&nbsp;Matthew B Roberts,&nbsp;Plinio R Hurtado,&nbsp;Stuart Turville,&nbsp;Branka Grubor-Bauk,&nbsp;Simon C Barry,&nbsp;Janakan Ravindran,&nbsp;Patrick Toby Coates,&nbsp;Pravin Hissaria","doi":"10.1002/cti2.70079","DOIUrl":"https://doi.org/10.1002/cti2.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We sought to identify determinants of vaccine response in people with multiple sclerosis (pwMS) receiving B-cell-depleting therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a prospective single-centre cohort study (ACTRN12623001249640). Peripheral blood samples were collected from pwMS receiving ocrelizumab (<i>n</i> = 38) before and after a third dose of COVID-19 mRNA vaccine. Immunogenicity was measured by T-cell IFN-γ ELISpot, antibody titres and live virus neutralisation. Humoral immunity was benchmarked against pwMS receiving natalizumab (<i>n</i> = 15), and against a correlate of real-world protection (50% reduction in incidence of infection). The peripheral immune phenotype was assessed by high-parameter flow cytometry and tested for association with vaccine response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD20⁺ T cells, natural killer (NK) cells and B cells were lower in pwMS receiving ocrelizumab, while CD27⁺CD38⁺ T-cell and CD8⁺ NK cell frequencies were elevated relative to natalizumab. Following a third dose, 51% of pwMS on ocrelizumab were seropositive for SARS-CoV-2 receptor-binding domain Ig, and 25% and 14% met the threshold for effective neutralisation of live ancestral and omicron BA.5 virus, respectively. B-cell frequency at the time of vaccination, but not time since ocrelizumab infusion, positively correlated with antibody response. Immunomodulatory CD56^bright NK cells were negatively associated with antibody response. CD3⁻CD20⁺ B cells (% of lymphocytes) and CD56^bright NK cells (% of NK cells) were associated with effective virus neutralisation in prior non-responders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Time since ocrelizumab infusion was not associated with protective vaccination. Evaluation of B-cell and CD56^bright NK cell frequencies may provide a personalised strategy to stratify pwMS for vaccination and prophylaxis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating mass spectrometry-based multi-omic signatures of extracellular vesicles: from discovery to clinical translation","authors":"Akila Wijerathna-Yapa,&nbsp;Dimitri Aubert,&nbsp;Arutha Kulasinghe","doi":"10.1002/cti2.70078","DOIUrl":"10.1002/cti2.70078","url":null,"abstract":"<p>Extracellular vesicles (EVs) are increasingly recognised as key mediators of intercellular communication and disease progression. Their capacity to carry bioactive molecules, namely proteins, lipids and metabolites, reflects the physiological and pathological states of their cells of origin, making them surrogates for diagnostic, prognostic and therapeutic endpoints. Recent advances in mass spectrometry have enabled comprehensive, high-resolution profiling of EVs across multiple omics layers. Proteomics has uncovered both conserved and disease-specific protein markers; lipidomics has revealed structurally distinct membrane compositions influencing EV stability and function; and metabolomics has captured dynamic snapshots of cellular metabolism. However, significant challenges persist for standardisation and interpretation of EVs, which include variation in EV isolation purity, scalability, EV heterogeneity and cross-study comparability. This perspective critically synthesises findings from recent EV multi-omics studies and proposes a conceptual framework for integrating these omics layers to better define EV identity and functionality. We highlight emerging clinical applications and outline future directions involving single-vesicle omics and the rational engineering of therapeutic EVs. The integration of multi-omics approaches with translational aims holds promise for advancing EVs from experimental tools to new pillars of precision medicine.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}