Pub Date : 2026-03-09eCollection Date: 2026-01-01DOI: 10.1002/cti2.70087
Xiaoxiao Jia, Isabelle Jh Foo, Hayley A McQuilten, Jeremy Chase Crawford, Aira F Cabug, Deborah Gebregzabher, Janet Chou, Robert C Mettelman, Tanya Novak, Lee-Ann Van de Velde, Ryan S Thwaites, Adrienne G Randolph, Paul G Thomas, Jianqing Xu, Zhongfang Wang, Katherine Kedzierska, Lukasz Kedzierski, Brendon Y Chua
Objectives: Our previous study in hospitalised patients infected with avian A(H7N9) influenza virus identified CD84 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.
Methods: Expression dynamics of CD84 and association with previously identified correlates of severe and fatal respiratory disease outcomes, OLAH and IL18R1, 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.
Results: Elevated CD84 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 CD84 expression persisted until discharge, while remaining low throughout the disease in patients that succumbed. We found inverse correlations between CD84 with OLAH and IL18R1 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.
Conclusion: 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.
{"title":"Influenza virus infection drives upregulation of CD84 across a broad range of immune cells.","authors":"Xiaoxiao Jia, Isabelle Jh Foo, Hayley A McQuilten, Jeremy Chase Crawford, Aira F Cabug, Deborah Gebregzabher, Janet Chou, Robert C Mettelman, Tanya Novak, Lee-Ann Van de Velde, Ryan S Thwaites, Adrienne G Randolph, Paul G Thomas, Jianqing Xu, Zhongfang Wang, Katherine Kedzierska, Lukasz Kedzierski, Brendon Y Chua","doi":"10.1002/cti2.70087","DOIUrl":"https://doi.org/10.1002/cti2.70087","url":null,"abstract":"<p><strong>Objectives: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 3","pages":"e70087"},"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}
Background: 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.
Methods: 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).
Results: 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.
Conclusions: 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.
{"title":"Integrated humoral and inflammatory signatures predict outcomes in severe COVID-19: a 14-day longitudinal analysis.","authors":"Hiochelson Najibe Santos Ibiapina, Fabio Magalhães-Gama, Juliana Costa Ferreira Neves, Fabíola Silva Alves-Hana, Ismael Artur Costa-Rocha, Alice Aparecida Lourenço, Ágata Lopes Ribeiro, Geovane Marques Ferreira, Thais Fernanda Campos Fraga-Silva, Adriana Alves Oliveira Paim, Daisymara Priscila Almeida Marques, Joaquim Pedro Brito-de-Sousa, Ana Carolina Campi-Azevedo, Vanessa Peruhype-Magalhães, Márcio Sobreira Silva Araújo, Andréa Teixeira-Carvalho, Vânia Luiza Deperon Bonato, Christiane Becari, Mayra Gonçalves Manegueti, Marcelo Cordeiro-Santos, Maria Auxiliadora-Martins, Jordana Grazziela Coelho-Dos-Reis, Olindo Assis Martins-Filho, Allyson Guimarães Costa","doi":"10.1002/cti2.70082","DOIUrl":"10.1002/cti2.70082","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusions: </strong>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>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 2","pages":"e70082"},"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}
Russell C Dale, Madysen Elbourne, Markus J Hofer, Shrujna Patel, Shekeeb Mohammad, Velda X Han, Josephine Yu, Shanlin Fu, Arlene D'Silva, Michelle A Farrar, Sushil Bandodkar, Jingya J Yan
Objective
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.
Methods
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.
Results
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 PFDR < 0.05). Using a targeted assay, we confirmed elevation of these metabolites in CSF, and also in the serum of patients with AGS (all P < 0.01).
Conclusion
Our findings suggest gut microbe metabolite leakage traversing the gut–blood–brain barrier in AGS, potentially because of endothelial dysfunction.
{"title":"Gut metabolites identified in cerebrospinal fluid of genetic interferonopathy support gut–brain endothelial dysfunction","authors":"Russell C Dale, Madysen Elbourne, Markus J Hofer, Shrujna Patel, Shekeeb Mohammad, Velda X Han, Josephine Yu, Shanlin Fu, Arlene D'Silva, Michelle A Farrar, Sushil Bandodkar, 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><sub>FDR</sub> < 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> < 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}
Fredrika Hellgren, Rodrigo Arcoverde Cerveira, Gustaf Lindgren, Puran Chen, Klara Lenart, Sebastian Ols, Alberto Cagigi, Davide Valentini, Mireia Rocavert Barranco, Evangelin Shaloom Vitus, Martin Corcoran, Yong-Dae Gwon, Mattias NE Forsell, Magnus Evander, COVAXID Study Group, Peter Bergman, Marcus Buggert, Hans-Gustaf Ljunggren, Soo Aleman, Gunilla B Karlsson Hedestam, Andreas Björklund, Anna Nordlander, Per Ljungman, Stephan Mielke, Karin Loré
Objectives
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.
Methods
Within the scope of a mRNA SARS-CoV-2 vaccine phase IV clinical trial in alloHCT recipients (n = 77), we have measured antibody titers and avidity, and performed B-cell immunophenotyping and B-cell receptor repertoire sequencing in sub-populations.
Results
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.
Conclusion
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.
{"title":"The impact of B-cell reconstitution on mRNA vaccine responses in allogeneic stem cell transplant recipients","authors":"Fredrika Hellgren, Rodrigo Arcoverde Cerveira, Gustaf Lindgren, Puran Chen, Klara Lenart, Sebastian Ols, Alberto Cagigi, Davide Valentini, Mireia Rocavert Barranco, Evangelin Shaloom Vitus, Martin Corcoran, Yong-Dae Gwon, Mattias NE Forsell, Magnus Evander, COVAXID Study Group, Peter Bergman, Marcus Buggert, Hans-Gustaf Ljunggren, Soo Aleman, Gunilla B Karlsson Hedestam, Andreas Björklund, Anna Nordlander, Per Ljungman, Stephan Mielke, 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}
Griffith B Perkins, Christopher M Hope, Cheng Sheng Chai, Matthew J Tunbridge, Sebastian Sterling, Kevin Webb, Joey Yap, Arthur Eng Lip Yeow, Makutiro G Masavuli, Jacqueline Scaffidi, James D Zuiani, Anouschka Akerman, Anupriya Aggarwal, Vanessa Milogiannakis, Matthew B Roberts, Plinio R Hurtado, Stuart Turville, Branka Grubor-Bauk, Simon C Barry, Janakan Ravindran, Patrick Toby Coates, Pravin Hissaria
Objectives
We sought to identify determinants of vaccine response in people with multiple sclerosis (pwMS) receiving B-cell-depleting therapies.
Methods
This was a prospective single-centre cohort study (ACTRN12623001249640). Peripheral blood samples were collected from pwMS receiving ocrelizumab (n = 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 (n = 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.
Results
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 CD56bright NK cells were negatively associated with antibody response. CD3−CD20+ B cells (% of lymphocytes) and CD56bright NK cells (% of NK cells) were associated with effective virus neutralisation in prior non-responders.
Conclusion
Time since ocrelizumab infusion was not associated with protective vaccination. Evaluation of B-cell and CD56bright NK cell frequencies may provide a personalised strategy to stratify pwMS for vaccination and prophylaxis.
{"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, Christopher M Hope, Cheng Sheng Chai, Matthew J Tunbridge, Sebastian Sterling, Kevin Webb, Joey Yap, Arthur Eng Lip Yeow, Makutiro G Masavuli, Jacqueline Scaffidi, James D Zuiani, Anouschka Akerman, Anupriya Aggarwal, Vanessa Milogiannakis, Matthew B Roberts, Plinio R Hurtado, Stuart Turville, Branka Grubor-Bauk, Simon C Barry, Janakan Ravindran, Patrick Toby Coates, 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<sup>+</sup> T cells, natural killer (NK) cells and B cells were lower in pwMS receiving ocrelizumab, while CD27<sup>+</sup>CD38<sup>+</sup> T-cell and CD8<sup>+</sup> 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<sup>bright</sup> NK cells were negatively associated with antibody response. CD3<sup>−</sup>CD20<sup>+</sup> B cells (% of lymphocytes) and CD56<sup>bright</sup> 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<sup>bright</sup> 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}
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.
{"title":"Integrating mass spectrometry-based multi-omic signatures of extracellular vesicles: from discovery to clinical translation","authors":"Akila Wijerathna-Yapa, Dimitri Aubert, 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}
Van Hieu Mai, Marisa Prasanpanich, Nicha Zungsontiporn, Krittiya Korphaisarn, Piyada Sitthideatphaiboon, Chatchawit Aporntewan, Poonchavist Chantranuwat, Nattiya Hirankarn, Chanida Vinayanuwattikun
Objectives
Circulating cytokines/chemokines are linked to checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). The tumor-immune microenvironment (TIME) plays a significant role in modulating a broad range of cytokines and chemokines. This study aimed to explore the crosstalk between circulating cytokines/chemokines and TIME, related to ICIs outcomes.
Methods
We conducted a prospective cohort study of 81 participants with advanced or recurrent NSCLC who received ICIs. Pretreatment comprehensive 27 cytokines/chemokines analysis, immunohistochemistry (IHC) for CD8, Treg/FOXP3, and PD-L1(22C3) TPS, and RNA sequencing were conducted. Demographic characteristics were integrated in the analysis to define the crosstalk of significant TIME-related signatures. Circulating neutrophil-to-lymphocyte ratio (NLR) and IHC tumor-infiltrated neutrophil density were evaluated to correlate systemic and local inflammatory states with ICIs response.
Results
Pretreatment plasma IL-6 and IL-8 were the significant cytokines correlated with surrogate ICIs responses and ICIs progression-free survival (PFS). Despite several correlations between cytokines/chemokines and CD8+ TILs, Treg/FOXP3+ TILs, neither pretreatment IL-6 nor IL-8 was correlated with intra-tumoral or stromal Treg/FOXP3+ TILs, CD8+ TILs, and PD-L1. Four active neutrophil-related gene signatures overlapped and were significantly correlated with better ICIs outcomes and lower IL-6 levels. Among 69 genes in 4 neutrophil-related gene signatures, the overexpression of TREM1, SORL1, and HSD17B11 significantly contributed and inversely correlated with CIBERSORT memory B cells. Clinically, the stratification by low levels of IL-6/IL-8 and low NLR identified a subgroup with significantly improved survival outcomes, whereas IHC tumor-infiltrated neutrophil counts did not show a similar association.
Conclusion
Our study reveals a potential mechanistic axis linking circulating IL-6 and IL-8 to tumor-associated neutrophils, memory B cells, and therapeutic response. These findings underscore the crucial role of synergistic treatment in augmenting the efficacy of ICIs. The crosstalk between neutrophils and B cells in the orchestration of ICIs therapy for NSCLC was further elucidated through the roles of HSD17B11, SORL1, and TREM1.
{"title":"A comprehensive analysis of the correlation between plasma cytokines/chemokines and tumor immune microenvironment signature influences the response of checkpoint inhibitors in advanced non-small-cell lung cancer","authors":"Van Hieu Mai, Marisa Prasanpanich, Nicha Zungsontiporn, Krittiya Korphaisarn, Piyada Sitthideatphaiboon, Chatchawit Aporntewan, Poonchavist Chantranuwat, Nattiya Hirankarn, Chanida Vinayanuwattikun","doi":"10.1002/cti2.70076","DOIUrl":"https://doi.org/10.1002/cti2.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Circulating cytokines/chemokines are linked to checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). The tumor-immune microenvironment (TIME) plays a significant role in modulating a broad range of cytokines and chemokines. This study aimed to explore the crosstalk between circulating cytokines/chemokines and TIME, related to ICIs outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective cohort study of 81 participants with advanced or recurrent NSCLC who received ICIs. Pretreatment comprehensive 27 cytokines/chemokines analysis, immunohistochemistry (IHC) for CD8, Treg/FOXP3, and PD-L1(22C3) TPS, and RNA sequencing were conducted. Demographic characteristics were integrated in the analysis to define the crosstalk of significant TIME-related signatures. Circulating neutrophil-to-lymphocyte ratio (NLR) and IHC tumor-infiltrated neutrophil density were evaluated to correlate systemic and local inflammatory states with ICIs response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pretreatment plasma IL-6 and IL-8 were the significant cytokines correlated with surrogate ICIs responses and ICIs progression-free survival (PFS). Despite several correlations between cytokines/chemokines and CD8<sup>+</sup> TILs, Treg/FOXP3<sup>+</sup> TILs, neither pretreatment IL-6 nor IL-8 was correlated with intra-tumoral or stromal Treg/FOXP3<sup>+</sup> TILs, CD8<sup>+</sup> TILs, and PD-L1. Four active neutrophil-related gene signatures overlapped and were significantly correlated with better ICIs outcomes and lower IL-6 levels. Among 69 genes in 4 neutrophil-related gene signatures, the overexpression of TREM1, SORL1, and HSD17B11 significantly contributed and inversely correlated with CIBERSORT memory B cells. Clinically, the stratification by low levels of IL-6/IL-8 and low NLR identified a subgroup with significantly improved survival outcomes, whereas IHC tumor-infiltrated neutrophil counts did not show a similar association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study reveals a potential mechanistic axis linking circulating IL-6 and IL-8 to tumor-associated neutrophils, memory B cells, and therapeutic response. These findings underscore the crucial role of synergistic treatment in augmenting the efficacy of ICIs. The crosstalk between neutrophils and B cells in the orchestration of ICIs therapy for NSCLC was further elucidated through the roles of HSD17B11, SORL1, and TREM1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987081","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}
Carole Nagant, Maxime Taghavi, Hasnae Ben Kacem Ziani, Nathalie Ghorra, Valérie Badot, Sarah Parmentier, Francis Corazza
Objectives
Anti-dsDNA antibodies are established biomarkers in systemic lupus erythematosus (SLE), yet the clinical utility of conventional assays remains limited by variable analytical performance. We evaluated a novel Fibre-Optic Surface Plasmon Resonance (FO-SPR) biosensor for real-time profiling of anti-dsDNA antibody–antigen interactions and investigated whether kinetic parameters are associated with disease severity, particularly lupus nephritis (LN).
Methods
Sera from 26 SLE patients (including 12 with LN), 14 disease controls and 16 healthy donors were analysed using FO-SPR biosensors coated with biotinylated dsDNA. The sensors generated real-time kinetic profiles from which maximum binding response (Bmax), association rate and dissociation constant were computed. FO-SPR kinetic results were compared with a conventional chemiluminescent anti-dsDNA assay (CLIA) and correlated with disease activity and renal involvement.
Results
The FO-SPR platform enabled reliable detection of anti-dsDNA antibodies and clearly distinguished SLE patients with renal involvement: Eight of 12 LN patients showed Bmax values above the 90th percentile of the non-SLE control group. In these patients, kinetic parameters revealed high-affinity anti-dsDNA profiles characterised by significantly higher association rates and maximal shifts and lower dissociation constants. The AUC-ROC for SPR-derived affinity parameters was 0.82 (P = 0.006), outperforming the CLIA assay to discriminate lupus patients with versus without nephritis. Furthermore, FO-SPR binding responses correlated with disease activity score in LN.
Conclusion
This study highlights the value of an innovative FO-SPR biosensor for real-time characterisation of anti-dsDNA antibody affinity. The kinetic profiles captured by this platform provide clinically relevant insights, particularly for distinguishing LN patients from other SLE phenotypes.
{"title":"A novel surface plasmon resonance approach to assess anti-dsDNA antibody kinetics and disease severity in systemic lupus erythematosus","authors":"Carole Nagant, Maxime Taghavi, Hasnae Ben Kacem Ziani, Nathalie Ghorra, Valérie Badot, Sarah Parmentier, Francis Corazza","doi":"10.1002/cti2.70072","DOIUrl":"https://doi.org/10.1002/cti2.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Anti-dsDNA antibodies are established biomarkers in systemic lupus erythematosus (SLE), yet the clinical utility of conventional assays remains limited by variable analytical performance. We evaluated a novel Fibre-Optic Surface Plasmon Resonance (FO-SPR) biosensor for real-time profiling of anti-dsDNA antibody–antigen interactions and investigated whether kinetic parameters are associated with disease severity, particularly lupus nephritis (LN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sera from 26 SLE patients (including 12 with LN), 14 disease controls and 16 healthy donors were analysed using FO-SPR biosensors coated with biotinylated dsDNA. The sensors generated real-time kinetic profiles from which maximum binding response (<i>B</i><sub>max</sub>), association rate and dissociation constant were computed. FO-SPR kinetic results were compared with a conventional chemiluminescent anti-dsDNA assay (CLIA) and correlated with disease activity and renal involvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The FO-SPR platform enabled reliable detection of anti-dsDNA antibodies and clearly distinguished SLE patients with renal involvement: Eight of 12 LN patients showed <i>B</i><sub>max</sub> values above the 90th percentile of the non-SLE control group. In these patients, kinetic parameters revealed high-affinity anti-dsDNA profiles characterised by significantly higher association rates and maximal shifts and lower dissociation constants. The AUC-ROC for SPR-derived affinity parameters was 0.82 (<i>P</i> = 0.006), outperforming the CLIA assay to discriminate lupus patients with versus without nephritis. Furthermore, FO-SPR binding responses correlated with disease activity score in LN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the value of an innovative FO-SPR biosensor for real-time characterisation of anti-dsDNA antibody affinity. The kinetic profiles captured by this platform provide clinically relevant insights, particularly for distinguishing LN patients from other SLE phenotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145969880","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}
Daniela Paasch, Hannah Schevel, Andrea Riehle, Bibiana Costa, Hassan Toufaili, Tabea Gehnen, Julia Dahlmann, Andreas Pavlou, Anna-Lena Neehus, Ariane Hai Ha Nguyen, Erika Schiering, Theresa Buchegger, Jacinta Bustamante, Gesine Hansen, Ulrich Kalinke, Erich Gulbins, Heike Grassmé, Nico Lachmann
Objectives
Tuberculosis (TB) remains a global health challenge, with current antibiotic therapies being limited by long treatments, side effects and multidrug-resistant mycobacterial strains. In addition, Mycobacterium tuberculosis (Mtb), the main causative agent of TB, employs evasion mechanisms particularly within alveolar macrophages being the primary host cells. Conventional therapies fail to modulate macrophage function or effectively target host immunity, which is crucial in TB pathogenesis. Emerging evidence points to induced pluripotent stem cell-derived macrophages (iMacs) with enhanced bactericidal activity as a promising cell-based approach for TB treatment. Therefore, this study aimed to compare iMacs with blood monocyte-derived macrophages (MDMs) in response to Bacillus Calmette–Guérin (BCG), the live attenuated TB vaccine and heat-killed Mtb (HKMT).
Methods
iMacs and MDMs were challenged with BCG and HKMT to assess their functional responses. Key parameters evaluated included cell migration, phagocytosis kinetics, levels of autophagy- and apoptosis-related proteins, and cytokine production profiles following infection.
Results
iMacs displayed enhanced migration, faster phagocytosis and increased expression of autophagy- and apoptosis-related proteins compared with MDMs. Moreover, iMacs showed a stronger pro-inflammatory cytokine response and rapid return to baseline cytokine levels post-infection.
Conclusion
These findings support the potential of iMacs as an immunocompetent model for studying mycobacterial infections and as a tool for cell-based TB immunotherapies.
{"title":"Immune activation and response dynamics of human iPSC-derived macrophages in tuberculosis infection models","authors":"Daniela Paasch, Hannah Schevel, Andrea Riehle, Bibiana Costa, Hassan Toufaili, Tabea Gehnen, Julia Dahlmann, Andreas Pavlou, Anna-Lena Neehus, Ariane Hai Ha Nguyen, Erika Schiering, Theresa Buchegger, Jacinta Bustamante, Gesine Hansen, Ulrich Kalinke, Erich Gulbins, Heike Grassmé, Nico Lachmann","doi":"10.1002/cti2.70071","DOIUrl":"https://doi.org/10.1002/cti2.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Tuberculosis (TB) remains a global health challenge, with current antibiotic therapies being limited by long treatments, side effects and multidrug-resistant mycobacterial strains. In addition, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), the main causative agent of TB, employs evasion mechanisms particularly within alveolar macrophages being the primary host cells. Conventional therapies fail to modulate macrophage function or effectively target host immunity, which is crucial in TB pathogenesis. Emerging evidence points to induced pluripotent stem cell-derived macrophages (iMacs) with enhanced bactericidal activity as a promising cell-based approach for TB treatment. Therefore, this study aimed to compare iMacs with blood monocyte-derived macrophages (MDMs) in response to Bacillus Calmette–Guérin (BCG), the live attenuated TB vaccine and heat-killed <i>Mtb</i> (HKMT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>iMacs and MDMs were challenged with BCG and HKMT to assess their functional responses. Key parameters evaluated included cell migration, phagocytosis kinetics, levels of autophagy- and apoptosis-related proteins, and cytokine production profiles following infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>iMacs displayed enhanced migration, faster phagocytosis and increased expression of autophagy- and apoptosis-related proteins compared with MDMs. Moreover, iMacs showed a stronger pro-inflammatory cytokine response and rapid return to baseline cytokine levels post-infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings support the potential of iMacs as an immunocompetent model for studying mycobacterial infections and as a tool for cell-based TB immunotherapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145983979","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}
Hyunkyung Cha, Jina Won, Soo Min Kim, Suhyun Lim, Sujin Kim, Siyeon Jin, Sung Dong Cho, Hyun Jik Kim
Objectives
Here, we characterised the diversity and persistence of immunological memory cells—particularly tissue-resident memory T (TRM) and B (BRM) cells—in the nasopharyngeal lymphoid tissues of healthy vaccinated (HV) individuals and those who experienced SARS-CoV-2 breakthrough infection (BR).
Methods
Nasopharynx (NP) samples were obtained using brushing from HV and BR subjects. Immune cell populations were analysed using transcriptomic profiling and flow cytometry.
Results
Transcriptomic profiling revealed that the NP of SARS-CoV-2-infected individuals exhibited distinctive signatures of lymphocyte-mediated immunity, underscoring its role as a key site for viral invasion and immune activation. Effector memory CD4+ and CD8+ T (TEM) cells, along with non-germinal center (GC) B cells, predominated in the NP. Although overall frequencies of memory T cells were comparable between HV and BR groups, CD4+ TEM and GC B cells were significantly enriched in the NP of BR individuals at least 1 year post infection. Notably, over 80% of CD4+ TEM and 40% of CD8+ TEM cells were TRM, and more than 30% of memory B cells exhibited a BRM phenotype. These populations of CD4+, CD8+ TRM and BRM persisted in the NP for over 2 years following SARS-CoV-2 infection or vaccination. In particular, CD4+ TRM cells were significantly more abundant and durably maintained in the NP mucosa of BR individuals.
Conclusion
Our findings identify the nasopharynx as a key site of long-lived immunological memory, marked by persistent TRM and BRM cells after SARS-CoV-2 exposure.
{"title":"Prolonged persistence of tissue-resident memory cells in the upper airway following SARS-CoV-2 infection and vaccination","authors":"Hyunkyung Cha, Jina Won, Soo Min Kim, Suhyun Lim, Sujin Kim, Siyeon Jin, Sung Dong Cho, Hyun Jik Kim","doi":"10.1002/cti2.70075","DOIUrl":"10.1002/cti2.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Here, we characterised the diversity and persistence of immunological memory cells—particularly tissue-resident memory T (T<sub>RM</sub>) and B (B<sub>RM</sub>) cells—in the nasopharyngeal lymphoid tissues of healthy vaccinated (HV) individuals and those who experienced SARS-CoV-2 breakthrough infection (BR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nasopharynx (NP) samples were obtained using brushing from HV and BR subjects. Immune cell populations were analysed using transcriptomic profiling and flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transcriptomic profiling revealed that the NP of SARS-CoV-2-infected individuals exhibited distinctive signatures of lymphocyte-mediated immunity, underscoring its role as a key site for viral invasion and immune activation. Effector memory CD4+ and CD8+ T (T<sub>EM</sub>) cells, along with non-germinal center (GC) B cells, predominated in the NP. Although overall frequencies of memory T cells were comparable between HV and BR groups, CD4+ T<sub>EM</sub> and GC B cells were significantly enriched in the NP of BR individuals at least 1 year post infection. Notably, over 80% of CD4+ T<sub>EM</sub> and 40% of CD8+ T<sub>EM</sub> cells were T<sub>RM</sub>, and more than 30% of memory B cells exhibited a B<sub>RM</sub> phenotype. These populations of CD4+, CD8+ T<sub>RM</sub> and B<sub>RM</sub> persisted in the NP for over 2 years following SARS-CoV-2 infection or vaccination. In particular, CD4+ T<sub>RM</sub> cells were significantly more abundant and durably maintained in the NP mucosa of BR individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings identify the nasopharynx as a key site of long-lived immunological memory, marked by persistent T<sub>RM</sub> and B<sub>RM</sub> cells after SARS-CoV-2 exposure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958286","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}
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