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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination

Fig. 3

Proline42-binding MOG Ab are the dominant IgG in serum of children and adults with demyelinating disorders. a Circular dichroism spectra of extracellular MOG (native-MOG1–117) and extracellular P42S (native-P42S1–117) domains showed characteristic minima at 215 nm, indicating β-sheet folding in both antigens. b and c High surface expression of native-P42S was comparable to native-MOG by immunocytochemistry (b) and flow cytometry (c). Scale bar = 20 μm. d 118/139 children (85%) and 113/148 adults (76%) harbored native-P42 Ab (orange), whereas 11/139 children (8%) and 21/148 (14%) adults had native-S42 Ab (blue). 10/139 paediatric (7%) and 14/149 (9%) adult sera recognized an unknown epitope on native-MOG (grey). Dotted line represents the control reference range determined by age-matched controls (n = 24 children, n = 24 adults). Number and percentage of patients in each epitope category are shown. e There was a positive correlation between native-P42 Ab titers in CSF and matched-serum in six children (diamonds) and six adults (triangles) (P = 0.006, R2 = 0.545). f Most patients with monophasic UON and BON recognized native-P42 (100%, 20/20 and 83%, 19/23, respectively, orange), whereas relapsing ON patients had lower titers of native-P42 Ab and were more likely to recognize an epitope outside P42 (blue or grey, P = 0.03, left). Percentage and number of native-P42 binders in each phenotype group are shown. 75% of adult patients with an epitope outside P42 (non-P42, n = 28) presented with a relapsing course (right). g Among patients with native-P42 and fixed-MOG Ab, most paediatric and adult sera recognized the P42 epitope in native-P42 and fixed-P42 conditions (77%, 53/69 children; 80%, 52/65 adults), whilst a group lost their binding to the P42 epitope when MOG was fixed (23%, 16/69 children; 20%, 13/65 adults). θMRW = mean residue weight ellipticity, Ab = antibody, BON = bilateral optic neuritis, CSF = cerebrospinal fluid, MFI = median fluorescence intensity, native-MOG1–117 = extracellular MOG, native-MOG = native human MOG, native-CTL = native transduced control cell, native-P42 Ab = native Proline42 binding MOG Ab, ON mixed = combination of BON and UON, S42 = Serine42, UON = unilateral optic neuritis

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