CLIC-1 antibody, present in patients with multiple sclerosis (MS) and relapsing inflammatory optic neuritis (RION), could serve as a biomarker for the differentiation between these conditions and neuromyelitis optica spectrum disorder (NMOSD), according to a recently published study in Multiple Sclerosis and Related Disorders.

Although not a typical presentation, some patients with multiple sclerosis present predominantly with optic neuritis and myelitis symptoms. The clinical similarity makes the differential diagnosis difficult, considering that a percentage of NMOSD are seronegative for antiaquaporin 4 antibodies.

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The autoimmune mechanisms present in NMOSD and MS appear to be similar. However, an in-depth analysis of the antibody profile of patients with this particular presentation of MS has yet to be performed.

Therefore, the authors aimed to discover novel antibodies targeting the astrocytic cell membrane by subjecting human IgG astrocyte immune precipitates to mass spectrometry analysis.

The study included samples from 29 patients with confirmed MS diagnosis according to McDonald’s 2017 criteria with a history of at least 1 attack of optic neuritis and 1 attack of myelitis and was seronegative for NMOSD antibodies. The study also included 36 patients with conventional relapsing-remitting MS, 30 patients with NMOSD, of which some were seronegative, 15 patients with RION, and 36 healthy controls.

Researchers identified antibodies targeting the CLIC1 channel protein in the astrocyte membrane were identified in 5 patients with MS with neuritis and myelitis attacks. A subsequent homemade ELISA using recombinant CLIC1 as the target antigen led to the identification of antiCLIC1 antibodies in 9 patients with optic neuritis and myelitis MS and 3 patients with RION. None of the patients with NMOSD were positive.

“CLIC1-antibody was identified for the first time in MS and RION patients, confirming once again antiastrocytic autoimmunity in CIDD. CLIC1-antibody may potentially be utilized as a diagnostic biomarker for differentiation of MS from NMOSD,” the authors concluded.


Karaaslan Z, Şengül-Yediel B, Yüceer-Korkmaz H, et al. Chloride intracellular channel protein-1 (CLIC1) antibody in multiple sclerosis patients with predominant optic nerve and spinal cord involvement. Mult Scler Relat Disord. Published online August 13, 2023. doi:10.1016/j.msard.2023.104940