Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis

Melania Spadaro; Lisa Ann Gerdes; Markus Krumbholz; Birgit Ertl-Wagner; Franziska Sabrina Thaler; Elisabeth Schuh; Imke Metz; Astrid Blaschek; Andrea Dick; Wolfgang Brück; Reinhard Hohlfeld; Edgar Meinl; Tania Kümpfel

doi:10.1212/NXI.0000000000000257

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Figure 1. Antibodies to MOG in a proportion of adult patients with MS
(A) Sera from 3 groups of patients with MS were analyzed for anti-MOG reactivity. Group 1: patients with MS with a specific clinical phenotype, namely, with severe or recurrent myelitis and/or severe (visual acuity <0.5) or recurrent optic neuritis, and/or brainstem syndrome (n = 104). Group 2: unselected patients with MS matched for age and sex (n = 55). Group 3: biopsied patients (n = 22), 4 with MS type II pathology (empty triangles). The red line indicates the cutoff for anti-MOG positivity. Values shown for each anti-MOG IgG–positive patient represent the mean of 3 independent measurements using the first serum sample analyzed, which was 14, 16, 3, 18, and 9 years after disease onset for patients 1 through 5. (B, C) Clinical features, therapies, and longitudinal analysis of antibodies to MOG in patients 1 and 2. (D) Analysis of the epitope specificity of the MOG reactivity of the samples indicated with asterisks (*) in C. Reactivity of the serum samples diluted 1:50 to the indicated variants of hMOG and to mMOG is shown. Values obtained with wild-type hMOG were set as 100% and the other reactivities were calculated as described.²² Depicted are the mean values of 3 independent experiments ± SEM. DMF = dimethyl fumarate; DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; FTY = fingolimod; GLAT = glatiramer acetate; hMOG = human myelin oligodendrocyte glycoprotein; IgG = immunoglobulin G; IVIG = IV immunoglobulins; MFI = mean fluorescence intensity; mMOG = mouse myelin oligodendrocyte glycoprotein; MOG = myelin oligodendrocyte glycoprotein; MS = multiple sclerosis; NAT = natalizumab; PLEX = plasma exchange; RX = rituximab.
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Figure 2. MRI features of patients with MS who had antibodies to myelin oligodendrocyte glycoprotein
(A) Patient 2: cerebral MRI showing typical MS deep white matter lesions (A.a, T2w, axial plane) and partially confluent callosal lesions (A.b, FLAIR, sagittal plane). Furthermore, bilateral lesions in the periaqueductal gray (A.c, T2w, A.d: magnified view) and bilateral pontomedullary lesions were observed (A.e, T2w, A.f: magnified view). sMRI displaying LETM and segmental atrophy in the lower thoracic and lumbar spinal cord (A.g, level T8-T11). (B) Patient 1: sMRI showing multiple partially confluent lesions in the cervical cord from C1-C6 (FLAIR, sagittal) and in the thoracic cord with focal atrophy. (C) Patient 3: sMRI demonstrating LETM from C2-C5 (FLAIR, sagittal). FLAIR = fluid-attenuated inversion recovery; LETM = longitudinally extensive transverse myelitis; MS = multiple sclerosis; sMRI = spinal MRI; T2w = T2-weighted.

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Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis

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