Ann Lab Med.  2024 Jan;44(1):56-63. 10.3343/alm.2024.44.1.56.

Clinical Usefulness of a Cell-based Assay for Detecting Myelin Oligodendrocyte Glycoprotein Antibodies in Central Nervous System Inflammatory Disorders

• Seok JM
• Waters P
• Jeon MY
• Lee HL
• Baek SH
• Park JS
• Kang SY
• Kwon O
• Oh J
• Kim BJ
• Park KA
• Oh SY
• Kim BJ
• Min JH

• KMID: 2550223
• DOI: http://doi.org/10.3343/alm.2024.44.1.56

Abstract

Background
The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients’ clinical characteristics.
Methods
We established the CBA using HEK 293 cells transiently overexpressing fulllength human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD).
Results
Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ = 0.883, P < 0.001); two patients (2/166, 1.2%) were only positive in our in-house CBA, and the CBA scores of the two laboratories correlated well (r = 0.663, P < 0.001). The commercial MOG-Ab CBA kit showed one falsenegative and three false-positive results. The clinical presentation at disease onset differed between MOGAD and NMOSD; ON was the most frequent manifestation in MOGAD, and transverse myelitis was most frequent in NMOSD.
Conclusions
The in-house CBA for MOG-Abs demonstrated reliable results and can potentially be used to evaluate CNS inflammatory disorders. A comprehensive, long-term study with a large patient population would clarify the clinical significance of MOG-Abs.

Keyword

Autoantibody; Central nervous system disease; Immunoassay; Myelin oligodendrocyte glycoprotein

Figure

• 

  Fig. 1 Representative results obtained with our in-house MOG-Ab CBA, showing different intensities. The intensities of 1+ to 4+ were assigned according to the description of the CBA scores (Supplemental Data Table S1). Photographs of the samples were acquired using our in-house MOG-Ab CBA with samples from different patients, including patient #49 (score: 2+), patient #66 (score: 3+), and patient #71 (score: 4+). The CBA score of 0 was observed with a negative control, and the score of 1+ was observed with a sample from a patient with MOG-Ab-associated disease who was not included in this study. Abbreviations: MOG-Ab, myelin oligodendrocyte glycoprotein autoantibody; CBA, cell-based assay.

• 

  Fig. 2 Positive results obtained with our in-house MOG-Ab CBA, according to different clinical diagnoses. Abbreviations: TM, transverse myelitis; ON, optic neuritis; MS, multiple sclerosis; SP-NMOSD, seropositive neuromyelitis optica spectrum disorder; SN-NMOSD, seronegative neuromyelitis optica spectrum disorder; ODD, other demyelinating disease; OND, other neurological disease; MOG-Ab, myelin oligodendrocyte glycoprotein autoantibody; CBA, cell-based assay.

• 

  Fig. 3 Scatter plot depicting the correlation of scores between our in-house MOG-Ab CBA and the Oxford MOG-Ab CBA. The CBA scores of both laboratories correlated well (r=0.663, P<0.001). The sizes of the circles represent the number of cases. Abbreviations: MOG-Ab, myelin oligodendrocyte glycoprotein autoantibody; CBA, cell-based assay.

• 

  Fig. 4 Clinical presentation and age of onset in MOGAD and SP-NMOSD. (A) The onset of MOGAD tended to occur at a younger age than that of seropositive NMOSD (34.2±16.6 yrs vs. 39.6±15.7 yrs, P=0.105). (B) The proportions of clinical syndromes at onset differed between patients with MOGAD and patients with SP-NMOSD (P=0.007). Abbreviations: TM, transverse myelitis; ON, optic neuritis; MOGAD, myelin oligodendrocyte glycoprotein autoantibody-associated disease; SP-NMOSD, seropositive neuromyelitis optica spectrum disorder.

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