Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation - Scorecard - MDSpire

Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation

  • By

  • Tilman Schneider-Hohendorf

  • Christian Wünsch

  • Simon Falk

  • Catarina Raposo

  • Florian Rubelt

  • Hamid Mirebrahim

  • Hosseinali Asgharian

  • Ulrich Schlecht

  • Daniel Mattox

  • Wenyu Zhou

  • Eva Dawin

  • Marc Pawlitzki

  • Sarah Lauks

  • Sven Jarius

  • Brigitte Wildemann

  • Joachim Havla

  • Tania Kümpfel

  • Miriam-Carolina Schrot

  • Marius Ringelstein

  • Markus Kraemer

  • Carolin Schwake

  • Thomas Schmitter

  • Ilya Ayzenberg

  • Katinka Fischer

  • Sven G Meuth

  • Orhan Aktas

  • Martin W Hümmert

  • Julian R Kretschmer

  • Corinna Trebst

  • Ilka Kleffner

  • Jennifer Massey

  • Paolo A Muraro

  • Haiyin Chen-Harris

  • Catharina C Gross

  • Luisa Klotz

  • Heinz Wiendl

  • Nicholas Schwab

  • July 18, 2024

  • 0 min

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Clinical Scorecard: Expanded TCR repertoire targeting EBV in multiple sclerosis: implications for disease specificity and therapeutic strategies

At a Glance

CategoryDetail
ConditionMultiple sclerosis (MS)
Key MechanismsAberrant MHC-I-restricted CD8+ T-cell receptor beta chain (TRB) repertoire targeting Epstein-Barr virus (EBV) with elevated but ineffective immune response
Target PopulationPatients with multiple sclerosis compared to healthy donors and patients with other CNS inflammatory diseases
Care SettingNeurology and immunology clinical settings managing MS and related CNS inflammatory diseases

Key Highlights

  • MS patients exhibit a broader EBV-specific MHC-I-restricted TRB repertoire compared to healthy controls and other CNS inflammatory diseases (NMOSD, MOGAD, Susac’s syndrome).
  • Approved MS therapies (ocrelizumab, teriflunomide, dimethyl fumarate) reduce EBV-specific but not CMV-specific MHC-I-restricted TRB sequence matches.
  • EBV reactivation during autologous haematopoietic stem-cell transplantation (AHSCT) coincides with elevated EBV-specific TRB sequences, indicating dynamic changes in EBV-specific T-cell responses.

Guideline-Based Recommendations

Diagnosis

  • Consider assessment of EBV-specific CD8+ T-cell receptor beta chain repertoire as a potential biomarker for MS specificity.
  • Differentiate MS from other CNS inflammatory diseases by evaluating EBV-specific TRB repertoire breadth.

Management

  • Use of MS therapies such as ocrelizumab, teriflunomide, and dimethyl fumarate may modulate aberrant EBV-specific T-cell responses.
  • Monitor EBV reactivation status especially in patients undergoing AHSCT.

Monitoring & Follow-up

  • Longitudinal TRB repertoire sequencing can detect EBV infection/reactivation and therapy effects on EBV-specific T-cell responses.
  • Monitor EBV-specific TRB sequence matches to evaluate treatment impact and disease activity.

Risks

  • Delayed primary EBV infection and aberrant EBV-specific T-cell responses may contribute to MS pathogenesis.
  • Potential EBV reactivation during immunosuppressive therapies such as AHSCT requires careful monitoring.

Patient & Prescribing Data

Patients with multiple sclerosis undergoing various disease-modifying therapies including AHSCT, ocrelizumab, teriflunomide, and dimethyl fumarate

Therapies targeting activated lymphocytes or EBV host cells reduce EBV-specific T-cell receptor repertoire breadth, potentially ameliorating aberrant immune responses linked to MS.

Clinical Best Practices

  • Incorporate EBV-specific TRB repertoire analysis in research and potentially clinical evaluation to distinguish MS from other CNS inflammatory disorders.
  • Monitor EBV reactivation especially in patients receiving AHSCT to guide management and anticipate immune changes.
  • Select MS therapies that have demonstrated reduction of EBV-specific T-cell responses to potentially improve disease outcomes.

References

Original Source(s)

Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation

  • by Tilman Schneider-Hohendorf, Christian Wünsch, Simon Falk, Catarina Raposo, Florian Rubelt, Hamid Mirebrahim, Hosseinali Asgharian, Ulrich Schlecht, Daniel Mattox, Wenyu Zhou, Eva Dawin, Marc Pawlitzki, Sarah Lauks, Sven Jarius, Brigitte Wildemann, Joachim Havla, Tania Kümpfel, Miriam-Carolina Schrot, Marius Ringelstein, Markus Kraemer, Carolin Schwake, Thomas Schmitter, Ilya Ayzenberg, Katinka Fischer, Sven G Meuth, Orhan Aktas, Martin W Hümmert, Julian R Kretschmer, Corinna Trebst, Ilka Kleffner, Jennifer Massey, Paolo A Muraro, Haiyin Chen-Harris, Catharina C Gross, Luisa Klotz, Heinz Wiendl, Nicholas Schwab

  • July 18, 2024

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