To determine the positive predictive value of serum MOG-IgG for clinically defined MOG-AD in a large institutional cohort study.

Myelin oligodendrocyte glycoprotein-associated disease (MOG-AD) is a monophasic or relapsing CNS demyelinating disease, typically presenting as optic neuritis, transverse myelitis, and/or ADEM-like syndromes. The positive predictive value (PPV) of serum MOG-IgG has been reported to range from 82-100%, dependent upon assays and study design (Waters et al. (2019)).

The Massachusetts General Brigham Research Patient Data Registry database was queried for patients with positive serum MOG-IgG detection, at least once, between January 1, 2017 and March 25, 2021. All were tested via the Mayo Clinic MOG-IgG1 fluorescence-activated cell sorting assay. MOG-IgG positive cases were reviewed for fulfillment of typical MOG-AD clinical features, determined by treating neurologists and study authors.

Of 80 patients who tested positive for MOG-IgG with titer >1:20 (44F; 36M; ages 5-81, median 37 years), 67 had validated MOG-AD, yielding PPV of 83.3%. Using a >1:40 titer cutoff, PPV was 93.8%. Three MOG positive cases had a prototypical multiple sclerosis diagnosis (RRMS n=2, 1:20 and 1:40; PPMS n=1; 1:100). The treating diagnosis for one RRMS patient with a 1:40 titer was subsequently modified to MOG-AD by treating neurologists. Validated diagnoses of the remaining positive patients without MOG-AD included: migraine (n=2, 1:20, 1:100), inclusion body myositis (n=1; 1:100), autoimmune encephalitis (n=2; 1:20, 1:20), hypoxic ischemic brain injury (n=1; 1:20), IgG4-related disease (n=1, 1:20), idiopathic hypertrophic pachymeningitis (n=1, 1:20) and cases of reported prior monophasic vision loss and sensory changes without supportive objective data (n=2; 1:20, 1:40).

In our cohort, PPV for MOG-IgG was 83.8% for titers >1:20 and 93.8% for titers >1:40, comparable to prior reports. The presence of positive cases with and without demyelinating features, emphasizes a need for appropriate ordering, analysis of titer value and appropriate clinical interpretation.