New Autoantibody Target Identified in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that targets astrocytes and can damage the brain, spinal cord, and optic nerve. Most patients carry antibodies against the astrocyte protein aquaporin-4, but a subset remains seronegative, making it difficult to distinguish NMOSD from other neurological autoimmune diseases. Identifying additional antibody targets could therefore refine testing in patients with NMOSD-like symptoms. 

Researchers at Friedrich-Alexander University Erlangen-Nürnberg (FAU) and collaborators identified autoantibodies against the membrane protein MLC1 and developed a cell-based test to detect them. The work began when patient serum applied to brain tissue sections produced a distinctive antibody staining pattern, prompting a targeted search for the underlying antigen. The team then pinpointed MLC1, a protein involved in regulating fluid and electrolyte balance and cell volume in the brain and spinal cord, as the autoantigen.

Image: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that attacks the brain, spinal cord, and optic nerve, primarily affecting astrocytes, , glial cells that provide essential support and maintenance functions in nerve tissue. (Image Credit: Adobe Stock)

In an international cohort of patients with inflammatory central nervous system diseases, the team identified four individuals who were positive for MLC1 autoantibodies; none tested positive for aquaporin-4 antibodies. Laboratory investigations showed that MLC1 antibodies bind to astrocytes and can damage or completely destroy them. The study was published in Science Translational Medicine on August 26, 2026, and involved LMU University Hospital Munich, the Medical University of Vienna, and additional research partners.

According to the authors, the findings expand understanding of NMOSD and NMOSD-like autoimmune diseases by indicating that an antibody-mediated immune response against astrocytes may be present even when aquaporin-4 antibodies are undetectable. Further studies will examine MLC1 antibodies in larger patient groups. The investigators state that mapping additional disease-relevant autoantibodies could improve differentiation across related neurological autoimmune conditions.

“The findings suggest that the studied autoantibodies are not merely an accompanying phenomenon but are involved in the processes that cause the disease,” said Simone Mader, head of Translational Immunology at Uniklinikum Erlangen.

“Identifying additional disease-relevant autoantibodies could help more precisely distinguish between the different forms of neurological autoimmune diseases. In the long term, such insights could also provide starting points for more targeted therapies,” Mader added.

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