Positive Predictive Value of MOG-IgG for Clinically Defined MOG-AD Within a Real-World Cohort

Abstract

Myelin oligodendrocyte glycoprotein antibody associated disease (MOG-AD) is a CNS demyelinating disease, typically presenting with optic neuritis, transverse myelitis, and/or ADEM-like syndromes. The positive predictive value (PPV) of MOG-IgG testing by live cell-based assay was reported to be 72% in a study performed at the Mayo Clinic using a cut-off of 1:20. PPV may vary depending upon the tested population, thus supporting further investigation of MOG-IgG testing at other centers. In this real-world institutional cohort study, we determined the PPV of serum MOG-IgG for clinically defined MOG-AD in our patient population. 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 MOG-IgG1 fluorescence-activated cell sorting assay (Mayo Laboratories, Rochester, MN). MOG-IgG positive cases were reviewed for fulfillment of typical MOG-AD clinical features, determined by treating neurologists and study authors. Of 1,877 patients tested, 78 (4.2%) patients tested positive for MOG-IgG with titer ≥1:20, and of these, 67 had validated MOG-AD yielding a PPV of 85.9%. Using a ≥1:40 titer cutoff, 65 (3.5%) tested positive and PPV was 93.8%. Three MOG positive cases had a prototypical multiple sclerosis diagnosis (RRMS n = 2, titers 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, titers 1:20, 1:100), inclusion body myositis (n = 1, titer 1:100), autoimmune encephalitis (n = 2, titers 1:20, 1:20), hypoxic ischemic brain injury (n = 1, titer 1:20), IgG4-related disease (n = 1, titer 1:20), and idiopathic hypertrophic pachymeningitis (n = 1, titer 1:20). In our cohort, the PPV for MOG-IgG improved utilizing a titer cut-off of ≥1:40. The presence of positive cases with and without demyelinating features, emphasizes a need for testing in the appropriate clinical context, analysis of titer value and clinical interpretation.

Obesity is associated with myelin oligodendrocyte glycoprotein antibody-associated disease in acute optic neuritis

“…Diagnosis of the underlying etiology was performed as part of the clinical routine and documented at follow-up visit respecting diagnostic criteria for MS according to the 2017 McDonald criteria 11 , NMOSD according to the 2015 international consensus diagnostic criteria and positive serum AQP4-IgG by cell-based assay 12 , and MOGAD at presentation in patients with clinical characteristics consistent with MOGAD-ON and positive serum MOG-IgG 13 . Serological testing for MOG-IgG was conducted at presentation in all optic neuritis patients presenting with findings suggestive of MOGAD, as proposed by Jarius et al in the international recommendations on diagnosis of MOGAD 14 . Testing for MOG-IgG in all MS patients is not warranted, as the positive predictive value for MOG-IgG is only 72%, and routine testing may lead to a significant increase in false positives 15 , 16 .…”

“…Testing for MOG-IgG in all MS patients is not warranted, as the positive predictive value for MOG-IgG is only 72%, and routine testing may lead to a significant increase in false positives 15 , 16 . Patients with AQP4-IgG+ NMOSD were not necessarily tested for MOG-IgG due to the rare coexistence of both antibodies 14 .…”

Clinical characteristics and associated factors of pediatric acute disseminated encephalomyelitis patients with MOG antibodies: a retrospective study in Hangzhou, China

“…The live cell-based MOG-IgG assay is a useful diagnostic tool for the determination of MOGAD, but sometimes it will lead to the potential for false positive results [ 22 ]. Previous studies showed that the positive predictive value (PPV) for MOG-IgG increased depending on the growth of the serum MOG-IgG titre cut-off.…”

Optic neuritis: current challenges in diagnosis and management

“…Sechi et al published titer dependent PPV as follows: 100% for 1:1000, 82% for 1:100, 51% for titers 1:20–1:40 [21 ▪▪ ]. In a study of 1877 patients, Manzano et al noted that a titer threshold of ≥1:40, rather than ≥1:20, improved the PPV for MOG-IgG from 85.9% to 92.3% [22 ▪ ]. Notably, numerical cut-off values need to be considered in the right clinical context, as PPV is dependent upon disease prevalence within a given population [22 ▪ ].…”