Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination

Table 2 Samples analyzed on murine organotypic brain slices and in the rat EAE model

			CBA			Tissue binding			Slice culture		Rat EAE
Sample ID	Sex/age (years)	Diagnosis	hMOG titer (1:)	rMOG titer (1:)	mMOG titer (1:)	Human tissue	Mouse tissue	Rat tissue	Total IgG used	MMS (range)	Total IgG used	DMS
MOG 1	F/4	MDEM	2560	160	2560	+	+	+	1 mg/ml	0 (0–1)	n.a.	n.a.
MOG 2	F/7	Rec-ON	2560	160	1280	+	−	+	1 mg/ml	0 (0–1)	n.a.	n.a.
MOG 3	F/8	NMOSD	1280	0	160	+	−	−	1 mg/ml	0 (0–2)	n.a.	n.a.
MOG 4	F/1	MDEM	2560	0	20	+	−	−	1 mg/ml	0 (0–1)	n.a.	n.a.
MOG 5	M/13	Rec-ON	1280	0	20	+	−	−	1 mg/ml	0 (0)	n.a.	n.a.
MOG 6	M/53	NMOSD	5120	0	1280	+	−	−	1 mg/ml	0 (0–1)	10 mg/ml	1
MOG 7	F/67	NMOSD	5120	5120	5120	+	+	+	1 mg/ml	1.5 (0–2)	10 mg/ml	1
MOG 8	F/5	MDEM	640	1280	640	+	+	+	1 mg/ml	0 (0–1)	n.a.	n.a.
MOG 9	F/15	ADEM	320	160	640	+	+	+	1 mg/ml	0 (0–1)	n.a.	n.a.
MOG 10	M/13	ADEM	2560	2560	2560	+	+	+	1 mg/ml	0 (0)	n.a.	n.a.
MOG 11	F/18	NMOSD	2660	0	1280	+	+	−	n.a.	n.a.	10 mg/ml	1
Ctrl 1	M/5	CIS-LETM	0	0	0	−	−	−	1 mg/ml	0 (0–1)	n.a.	n.a.
Ctrl 2	M/10	ADEM	0	0	0	−	−	+	1 mg/ml	0 (0–1)	n.a.	n.a.
Ctrl 3	F/18	MS	0	0	0	−	−	−	1 mg/ml	0 (0)	n.a.	n.a.
Ctrl 4	M/8	ADEM	0	0	0	−	−	−	n.a.	n.a.	10 mg/ml	1
HC 1	F/22	HC	0	0	0	−	−	−	1 mg/ml	0 (0–1)	n.a.	n.a.
HC 2	M/27	HC	0	0	0	−	−	−	1 mg/ml	0 (0)	n.a.	n.a.
HC 3	F/27	HC	0	0	0	−	−	−	1 mg/ml	0 (0–1)	n.a.	n.a.
h8-18-C5			> 40,960	> 40,960	> 40,960	+	+	+	10 μg/ml	3 (2–3)	n.a.	n.a.
m8-18-C5			> 40,960	> 40,960	> 40,960	+	+	+	n.a.	n.a.	5 mg/ml	4
Subcuvia			0	0	0	−	−	−	n.a.	n.a.	10 mg/ml	1
PBS			0	0	0	−	−	−	−	0 (0–1)	n.a.	n.a.

All samples were tested for MOG antibody reactivity on a live cell-based assay (CBA) and on human rat and mouse brain tissue. Slice cultures were evaluated with a median myelin score (MMS) ranging from 0 to 3 (0 = healthy myelin with well-preserved myelin sheath around myelinated axons, 1 = slight MBP degradation and myelin disruption, 2 = partial myelin loss, intermediate to severe MBP damage, 3 = almost complete loss of myelin along myelinated axons and severe MBP loss). Demyelination in the rat EAE model was evaluated with a median demyelination score (DMS) ranging from 0 to 4 (0 = no lesions/slice, 1 = one minor lesion/slice, 0.05–0.2 mm diameter, 2 = two minor lesions/slice or one medium lesion, > 0.2 mm diameter, 3 = two or more medium lesions/slice, 4 = significant loss of myelin)
Abbreviations: MOG 1-11 MOG antibody-positive patients, Ctrl 1-4 MOG antibody-negative patients, HC 1-3 healthy controls, Subcuvia normal human serum, h8-18-C5 humanized 8-18-C5 monoclonal MOG antibody, m8-18-C5 mouse 8-18-C5 monoclonal MOG antibody, F female, M male, ADEM acute demyelinating encephalomyelitis, CIS-LETM clinically isolated syndrome longitudinally extensive transverse myelitis, MDEM multiphasic demyelinating encephalomyelitis, NMOSD neuromyelitis optica spectrum disorders, rec-ON recurrent optic neuritis, MS multiple sclerosis, n.a. not analyzed

ISSN: 1742-2094