T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients
IndroductionMultiple sclerosis (MS) is mediated by innate and adaptive immune response deviation involving immune cells and cytokines. Here, we investigated whether combined cytokine profiling and T-cell receptor (TCR) repertoire analysis can better display the complex landscape of MS-driving immune...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604452/full |
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| author | Lisa Weidner Lisa Weidner Rodolphe Poupardin Tobias Zrzavy Sandra Laner-Plamberger Georg Gratz Tanja Eichhorn Viktoria Weber Paulus S. Rommer Christof Jungbauer Christof Jungbauer Dirk Strunk Dirk Strunk |
| author_facet | Lisa Weidner Lisa Weidner Rodolphe Poupardin Tobias Zrzavy Sandra Laner-Plamberger Georg Gratz Tanja Eichhorn Viktoria Weber Paulus S. Rommer Christof Jungbauer Christof Jungbauer Dirk Strunk Dirk Strunk |
| author_sort | Lisa Weidner |
| collection | DOAJ |
| description | IndroductionMultiple sclerosis (MS) is mediated by innate and adaptive immune response deviation involving immune cells and cytokines. Here, we investigated whether combined cytokine profiling and T-cell receptor (TCR) repertoire analysis can better display the complex landscape of MS-driving immune responses.MethodsWe used advanced computational methods to systematically cluster highly variable individual levels of 48 cytokines in cerebrospinal fluid (CSF) and blood of 24 MS patients compared to that of nine controls. Relevant TCR sequences were compared to 88 healthy controls. We correlated cytokines with predominant shared TCR sequences to identify immune response networks.ResultsMS patients had significantly elevated MIP-1α and IP-10 levels in CSF, and additional 36 blood cytokines variably but significantly elevated. We identified 77 predominantly pro-inflammatory cytokine correlations in MS-CSF. TCR sequencing revealed more productive rearrangements in CSF of MS and a significantly higher shared clone recovery rate in blood. We found significant associations involving 492 unique sequences and 34 cytokines in blood. Particularly, the less significant individual cytokine deviations were found to contribute to a general Th1-biased type I immune response correlating with clonal expansion of T cells directed against EBV, CMV, and other infectious agents.DiscussionCorrelation of significantly altered T-cell repertoire with cytokine deviations in MS despite individual patient data variability indicates that future diagnostic strategies may need to address immune response patterns rather than individual protein targets. |
| format | Article |
| id | doaj-art-635babe573d04ffd88e5755b3aba804b |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-635babe573d04ffd88e5755b3aba804b2025-08-20T03:16:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16044521604452T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patientsLisa Weidner0Lisa Weidner1Rodolphe Poupardin2Tobias Zrzavy3Sandra Laner-Plamberger4Georg Gratz5Tanja Eichhorn6Viktoria Weber7Paulus S. Rommer8Christof Jungbauer9Christof Jungbauer10Dirk Strunk11Dirk Strunk12Blood Service for Vienna, Lower Austria and Burgenland, Austrian Red Cross, Vienna, AustriaDepartment for Transfusion Medicine, University Hospital (SALK), Paracelsus Medical University (PMU), Salzburg, AustriaCell Therapy Institute, Paracelsus Medical University, Salzburg, AustriaDepartment of Neurology, Medical University of Vienna, Vienna, AustriaDepartment for Transfusion Medicine, University Hospital (SALK), Paracelsus Medical University (PMU), Salzburg, AustriaBlood Service for Vienna, Lower Austria and Burgenland, Austrian Red Cross, Vienna, AustriaDepartment for Biomedical Research, Center for Biomedical Technology, University for Continuing Education Krems, Krems, AustriaDepartment for Biomedical Research, Center for Biomedical Technology, University for Continuing Education Krems, Krems, AustriaDepartment of Neurology, Medical University of Vienna, Vienna, AustriaBlood Service for Vienna, Lower Austria and Burgenland, Austrian Red Cross, Vienna, AustriaDepartment for Transfusion Medicine, University Hospital (SALK), Paracelsus Medical University (PMU), Salzburg, AustriaBlood Service for Vienna, Lower Austria and Burgenland, Austrian Red Cross, Vienna, AustriaCell Therapy Institute, Paracelsus Medical University, Salzburg, AustriaIndroductionMultiple sclerosis (MS) is mediated by innate and adaptive immune response deviation involving immune cells and cytokines. Here, we investigated whether combined cytokine profiling and T-cell receptor (TCR) repertoire analysis can better display the complex landscape of MS-driving immune responses.MethodsWe used advanced computational methods to systematically cluster highly variable individual levels of 48 cytokines in cerebrospinal fluid (CSF) and blood of 24 MS patients compared to that of nine controls. Relevant TCR sequences were compared to 88 healthy controls. We correlated cytokines with predominant shared TCR sequences to identify immune response networks.ResultsMS patients had significantly elevated MIP-1α and IP-10 levels in CSF, and additional 36 blood cytokines variably but significantly elevated. We identified 77 predominantly pro-inflammatory cytokine correlations in MS-CSF. TCR sequencing revealed more productive rearrangements in CSF of MS and a significantly higher shared clone recovery rate in blood. We found significant associations involving 492 unique sequences and 34 cytokines in blood. Particularly, the less significant individual cytokine deviations were found to contribute to a general Th1-biased type I immune response correlating with clonal expansion of T cells directed against EBV, CMV, and other infectious agents.DiscussionCorrelation of significantly altered T-cell repertoire with cytokine deviations in MS despite individual patient data variability indicates that future diagnostic strategies may need to address immune response patterns rather than individual protein targets.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604452/fullneurosciencemultiple sclerosisT cell repertoirecytokine imbalancebioinformatics |
| spellingShingle | Lisa Weidner Lisa Weidner Rodolphe Poupardin Tobias Zrzavy Sandra Laner-Plamberger Georg Gratz Tanja Eichhorn Viktoria Weber Paulus S. Rommer Christof Jungbauer Christof Jungbauer Dirk Strunk Dirk Strunk T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients Frontiers in Immunology neuroscience multiple sclerosis T cell repertoire cytokine imbalance bioinformatics |
| title | T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients |
| title_full | T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients |
| title_fullStr | T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients |
| title_full_unstemmed | T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients |
| title_short | T-cell repertoire correlates with cytokine imbalance in multiple sclerosis patients |
| title_sort | t cell repertoire correlates with cytokine imbalance in multiple sclerosis patients |
| topic | neuroscience multiple sclerosis T cell repertoire cytokine imbalance bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604452/full |
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