Intrathecal T-cell clonal expansions in patients with multiple sclerosis

Area of Science:

• Immunology
• Neuroscience
• Genomics

Background:

• T-cell receptor (TCR) repertoire analysis in cerebrospinal fluid (CSF) offers insights into antigen-specific immune responses in neurological diseases.
• Multiple sclerosis (MS) is a demyelinating disease where T-cell involvement is crucial, but intrathecal immune responses remain incompletely understood.

Purpose of the Study:

• To apply a novel unbiased deep-sequencing method for comprehensive TCR repertoire analysis.
• To compare T-cell receptor diversity and clonal expansions in peripheral blood and CSF between MS patients and controls with idiopathic intracranial hypertension (IIH).

Main Methods:

• Deep sequencing of TCR β-chain libraries from paired blood and CSF samples.
• Analysis included five MS patients and five IIH controls, generating approximately 80 million reads.
• Quantification of TCR repertoire diversity and identification of clonal expansions within T-cell populations.

Main Results:

• MS patients exhibited significantly higher TCR repertoire diversity in both blood and CSF compared to IIH controls.
• The frequency of T-cell clonal expansions was notably higher in both compartments of MS patients.
• Highly expanded T-cell clones were enriched in the CSF of MS patients, with limited overlap between CSF and peripheral blood.

Conclusions:

• The study demonstrates compartmentalized T-cell expansion within the intrathecal space of MS patients.
• These findings provide proof of principle for private, disease-specific immune signatures in the MS central nervous system.