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Study Finds T-Cell Attack on Neuronal Protein in ALS, Strengthening Autoimmune Case

The Nature study connects CD4+ reactivity to C9orf72 with prognosis in ALS, suggesting immune targets that will require rigorous validation.

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Tanner Michaelis, a research technician, grabs a blood sample on Tuesday, Sept. 30, 2025 in La Jolla, CA. (Ana Ramirez / The San Diego Union-Tribune)

Overview

  • Researchers from La Jolla Institute for Immunology and Columbia University analyzed blood from 40 ALS patients and 28 controls, finding heightened CD4+ T-cell responses to the neuronal protein C9orf72 compared with other ALS-linked proteins.
  • T-cell reactivity was strongest in patients carrying C9orf72 mutations yet was observed across many patients, pointing to broader immune involvement beyond genetic subtypes.
  • Two immune profiles correlated with projected survival: a predominantly pro-inflammatory CD4+ response linked to shorter survival and a profile with additional anti-inflammatory CD4+ T cells, including higher IL-10, linked to longer survival.
  • Authors and outside experts say the results support an autoimmune component in ALS but do not prove causation, underscoring the need for replication, mechanistic studies, larger cohorts, and standardized assays.
  • The work raises prospects for immune profiling as a prognostic tool and for testing immune-modulatory strategies, such as training and reinfusing protective T cells or immunizing in an anti-inflammatory context.