ALS study links distinct blood and CSF T-cell profiles to disease progression

Researchers profiled paired blood and CSF samples from 20 patients with sporadic ALS around diagnosis, before riluzole treatment, using single-cell RNA and T-cell receptor sequencing. They also used imaging flow cytometry to assess immune-cell complexes. Comparisons included CSF data from 20 age- and sex-matched healthy controls. The analyses identified long-lived T-cell clonotypes in CSF and cell complexes with features consistent with antigen presentation.

Higher CSF frequencies of CD4 effector, CD4 regulatory and CD8 T cells were associated with slower disease progression. In contrast, higher circulating CD4 effector and regulatory T-cell frequencies were associated with faster progression. Cytomegalovirus-specific T-cell frequencies in CSF and serum anti-cytomegalovirus antibodies were associated with faster progression and shorter survival in sporadic ALS.

The findings suggest that immune associations differ between the blood and CSF compartments. They are observational associations and do not establish that these immune responses cause progression or that altering them would improve outcomes. The reported cohort was small, and the results do not support changes to clinical management.