International multicenter examination of MOG antibody assays

Reindl, Markus; Schanda, Kathrin; Woodhall, Mark; Charabati, Marc; Ramanathan, Sudarshini; Sagen, Jessica; Fryer, James P.; Mills, John R.; Teegen, Bianca; Mindorf, Swantje; Ritter, Nora; Krummrei, Ulrike; Stöcker, W.; Eggert, Juliane; Flanagan, Eoin P.; Ramberger, Melanie; Hegen, Harald; Rostásy, Kevin; Berger, Thomas; Leite, Maria Isabel; Palace, Jacqueline; Irani, Sarosh R.; Dale, Russell C.; Probst, Christian; Probst, Monika; Brilot, Fabienne; Pittock, Sean J.; Waters, Patrick

doi:10.1212/nxi.0000000000000674

Cited by 206 publications

(214 citation statements)

References 35 publications

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“…MOG-IgG serostatus was determined exclusively using CBAs with full-length human MOG, given that MOG-IgG detected by ELISA or Western blot lacks disease specificity. Notably, commonly used MOG-IgG CBAs demonstrate overall good agreement for high-positive and negative samples, although agreement is lower for borderline results, and this is another factor that could potentially influence diagnostic accuracy in the included studies ( 112 ).…”

Section: Discussionmentioning

confidence: 99%

AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

et al. 2020

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Background: Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease. However, the prevalence of AQP4-IgG seropositivity and MOG-IgG seropositivity in isolated ON is unclear, and studies comparing visual outcomes and optical coherence tomography (OCT)-derived structural retinal measures between MS-ON, AQP4-ON, and MOG-ON eyes are limited by small sample sizes. Objectives: (1) To assess the prevalence of AQP4-IgG and MOG-IgG seropositivity among patients presenting with isolated ON; (2) to compare visual outcomes and OCT measures between AQP4-ON, MOG-ON, and MS-ON eyes. Methods: In this systematic review and meta-analysis, a total of 65 eligible studies were identified by PubMed search. Statistical analyses were performed with random effects models. Results: In adults with isolated ON, AQP4-IgG seroprevalence was 4% in non-Asian and 27% in Asian populations, whereas MOG-IgG seroprevalence was 8 and 20%, respectively. In children, AQP4-IgG seroprevalence was 0.4% in non-Asian and 15% in Asian populations, whereas MOG-IgG seroprevalence was 47 and 31%, respectively. AQP4-ON eyes had lower peri-papillary retinal nerve fiber layer (pRNFL; −11.7 μm, 95% CI: −15.2 to −8.3 μm) and macular ganglion cell + inner plexiform layer (GCIPL; −9.0 μm, 95% CI: −12.5 to −5.4 μm) thicknesses compared with MS-ON eyes. Similarly, pRNFL (−11.2 μm, 95% CI: −21.5 to −0.9 μm) and GCIPL (−6.1 μm, 95% CI: −10.8 to −1.3 μm) thicknesses were lower in MOG-ON compared to MS-ON eyes, but did not differ between AQP4-ON and MOG-ON eyes (pRNFL: −1.9 μm, 95% CI: −9.1 to 5.4 μm; GCIPL: −2.6 μm, 95% CI: −8.9 to 3.8 μm). Visual outcomes were worse in AQP4-ON compared to both MOG-ON (mean logMAR difference: 0.60, 95% CI: 0.39 to 0.81) and MS-ON eyes (mean logMAR difference: 0.68, 95% CI: 0.40 to 0.96) but were similar in MOG-ON and MS-ON eyes (mean logMAR difference: 0.04, 95% CI: −0.05 to 0.14). Conclusions: AQP4-IgG- and MOG-IgG-associated disease are important diagnostic considerations in adults presenting with isolated ON, especially in Asian populations. Furthermore, MOG-IgG seroprevalence is especially high in pediatric isolated ON, in both non-Asian and Asian populations. Despite a similar severity of GCIPL and pRNFL thinning in AQP4-ON and MOG-ON, AQP4-ON is associated with markedly worse visual outcomes.

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Section: Discussionmentioning

confidence: 99%

AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

et al. 2020

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“…However, it is very likely that AQP4-ab testing was either done with a live cell-based assay (CBA) or with the well-evaluated Euroimmun kit ( 13 ). MOG-ab testing is possible with an Euroimmun kit as well, though the sensitivity and specificity are not as high as established live CBAs ( 47 ). Treating doctors might have sent serum samples to neuroimmunology labs in Heidelberg (S. Jarius) or in Kiel (F. Leypoldt), which both use the above-mentioned live CBAs.…”

Section: Methodsmentioning

confidence: 99%

“…Serum samples were analyzed for the presence of MOG-and AQP4-abs by live cell-based immunofluorescence assays as previously described (46,47).…”

Section: Antibody Assaysmentioning

confidence: 99%

Epidemiology of Pediatric NMOSD in Germany and Austria

et al. 2020

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Background: Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory demyelinating disorders of the central nervous system mainly characterized by recurrent episodes of uni-or bilateral optic neuritis (ON), transverse myelitis (TM) and brainstem syndromes (BS). The majority of adult patients has serum antibodies directed against the water channel protein aquaporin 4 (AQP4-abs). In pediatric patients, AQP4-abs are less, while antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) are more frequently detectable than in adults. Some children with NMOSD have neither AQP4-nor MOG-ab (double-seronegative). Objective: Evaluation of epidemiological data regarding incidence and prevalence of pediatric NMOSD in Germany and Austria. Methods: We recruited pediatric NMOSD patients between 1 March 2017 and 28 February 2019 with five different tools: (1) ESPED (Surveillance Unit for Rare Pediatric Disorders in Germany), (2) ESNEK (Surveillance for Rare Neurological Disorders during Childhood), (3) pediatric neurology working group within the Austrian Society of Pediatrics and Adolescent Medicine, (4) BIOMARKER Study and (5) NEMOS (Neuromyelitis optica Study Group). We requested data regarding clinical symptoms, antibody status, therapy regimen and response via a standardized questionnaire. Results: During the 2-year recruitment period, 46 (both incidental and prevalent) patients with a suspected diagnosis of NMOSD were brought to our attention. Twenty-two of these patients did not fulfill the inclusion criteria. Of the remaining 24 children, 22 had a median age at onset of 11 (range 3-17) years and 16/22 were female (72.7%) (no data in two patients). Sixteen of 24 patients were AQP4-ab positive (67%), 4/24 MOG-ab positive (16.7%), three children were double-seronegative and in one patient no antibody testing was done. We calculated an incidence rate of 0.022 per 100,000 person-years for Germany, while there was no incidental case in Austria during the recruitment period. The prevalence rate was 0.147 and 0.267 per 100,000 persons in Germany and Austria, respectively. Lechner et al. Epidemiology of Pediatric NMOSD Conclusion: Pediatric NMOSD, with and without associated antibodies, are very rare even considering the different limitations of our study. An unexpected finding was that a considerable proportion of patients was tested neither for AQP4-nor MOGabs during diagnostic work-up, which should prompt to establish and disseminate appropriate guidelines.

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“…Sera were tested at dilutions of 1:20 and 1:40 and MOG-Ab positivity was titrated with serial dilutions with a threshold of 1:160 to define MOG-Ab positivity. Isolated IgM reactivity was excluded using IgG constant chain (Fc)-specific secondary antibodies (48,49).…”

Section: Aqp4-ab and Mog-ab Detection Assaysmentioning

confidence: 99%