Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

Held, Friederike; Kalluri, Sudhakar Reddy; Berthele, Achim; Klein, Ana-Katharina; Reindl, Markus; Hemmer, Bernhard

doi:10.1177/20552173211022767

Cited by 26 publications

(28 citation statements)

References 51 publications

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“…Among the eleven false positive cases in our cohort, three had CNS demyelinating disease, albeit multiple sclerosis, and five patients had other neuroimmunologic conditions ( Table 2 ). However, three patients had non-neuroimmunologic conditions, and low levels of MOG-IgG have been detected in patients with diverse neuroimmunologic and non-neuroimmunologic diagnoses previously ( 14 ). The clinical relevance of MOG-IgG positivity in patients with atypical phenotypes for MOG-AD and/or more likely alternative diagnoses, such as multiple sclerosis, is thus an area that would benefit from future exploration ( 13 , 15 ).…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 97%

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

et al. 2022

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“…Importantly, antibody positivity is not always sufficient to guarantee a correct diagnosis of MOGAD (144). Despite the high specificity of CBAs for MOG-IgG, false positive results may occur, especially when the test is performed indiscriminately in large unselected populations (137,145). When MOG-IgG testing is ordered, a thorough phenotypical assessment is mandatory to determine the pre-test probability.…”

Section: Atypical Clinical-mri Phenotypes and Risk Of False Positivitymentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

et al. 2022

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Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

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“…In the latter case, MOG-IgG detection would rather represent a “true” positive, although clinically irrelevant, test result. 12 …”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Myelin Oligodendrocyte Glycoprotein Autoantibodies in Patients with Typical MS Lesions on MRI

Zara

Floris

Flanagan

et al. 2021

Multiple Sclerosis Journal - Experimental, Translational and Cl

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Background Myelin-oligodendrocyte-glycoprotein (MOG)-IgG-positivity in patients with typical MS lesions on MRI may lead to diagnostic/therapeutic uncertainty. Objective and Methods We reviewed reports of cases with MS phenotype on MRI and MOG-IgG-positivity published in Pubmed between 01/2012–06/2021. Results Sixteen patients were included (median age [range], 37,5 [25–66] years; 60% female). Three patients initially tested negative for MOG-IgG. Disease course was: relapsing-remitting, 10; or progressive, 6. Intrathecal IgG-synthesis was common (79%). Low and high-efficacy MS-targeted agents prevented relapses in 30% and 100%, respectively. None of the patients showed resolution of MRI T2-lesions over time. Conclusions MOG-IgG-positivity is unlikely to alter the expected treatment response and outcomes in patients with otherwise typical MS phenotype on MRI.

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Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

Cited by 26 publications

References 51 publications

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

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

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Clinical Significance of Myelin Oligodendrocyte Glycoprotein Autoantibodies in Patients with Typical MS Lesions on MRI

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