Four new autoantigens trigger multiple sclerosis

Despite considerable progress in the treatment of multiplesclerosis (MS), the disease still often leads to permanent neurological disability. Identifying autoantigens, which are targets of a misdirected immune response within the central nervous system that is believed to cause the disease, is key for improving MS diagnosis and treatment. However, autoantigens involved in MS have remained largely uncharacterised. To advance this research, Mattias Bronge and colleagues sampled blood cells from a total of 108 patients with MS, a total of 57 healthy controls, and 19 patients with other neurological diseases as an additional control group in one of the largest studies ever (doi: 10.1126/sciadv.abn1823).

They screened these samples for T-cell reactivity against fragments of a panel of 63 different proteins, which included both completely new and previously suspected antigens expressed in the central nervous system. The researchers found that four proteins contained antigens that were targeted by T-cells from patients with MS: fatty acid binding protein 7 (FABP7); prokineticin-2 (PROK2), reticulon-3 (RTN3), and synaptosome-associated protein 91kDa (SNAP91).

Next, Bronge et al. immunised mice with the novel autoantigens, confirming that all four led to significantly elevated levels of pro-inflammatory cytokines, indicating autoimmune activity. Male mice had a stronger response to the autoantigens overall, even though females are at higher risk for MS; this finding aligns with studies that have shown males tend to have a more aggressive form of the disease when they do develop it.