Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

Sinmaz, Nese; Nguyen, Tina; Tea, Fiona; Dale, Russell C.; Brilot, Fabienne

doi:10.1186/s12974-016-0678-4

Journal of Neuroinflammation

Table 1 Epitope target(s) of CNS and PNS human autoantibodies

From: Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

	CNS/PNS disorder	Antigen	Target: extra/intra	Main epitope	Other epitopes	Number of N-glycosylation sites	Sample type	Methodology	Reference
CNS	Anti-NMDAR encephalitis	Neuronal NMDAR	Extra	GluN1/NR1 subunit (ATD, N368/G369)	–	10 (N368^a)	CSF	Subcloning/ICC	Gleichman et al. [35]
	SLE	Neuronal NMDAR	Extra	NR2A/2B subunit (LBD/S1, aa283–287)		6	Sera/CSF	Phage display peptide library	DeGiorgio et al. [67].
	Anti-AMPAR encephalitis	Neuronal AMPAR	Extra	GluR1 subunit (Bottom of ATD)	S1 domain	6	Sera/CSF	Subcloning/ICC, Fusion protein-based western blot	Gleichman et al. [32]
	Autoimmune encephalitis	Neuronal Caspr2	Extra	Disc domain	Lam1, Lam2, Egf1 domains	12	Sera	Subcloning/ICC, western blot	Olsen et al. [37]
	Autoimmune encephalitis	Neuronal Caspr2	Extra	Disc, Lam1 domains	–	12	Sera/CSF	Flow cytometry cell-based assay	Pinatel et al. [38]
	Encephalitis/SPS	Neuronal GAD65	Intra	Catalytic region (aa221-444)	C-terminal domain	0	Sera	Immunoprecipitation assay	Fouka et al. [48]
	Encephalitis/SPS	Neuronal GAD65	Intra	aa4-22, aa308-365, aa451-585	–	0	Sera	Competition assay	Raju et al. [47]
	NMOSD/BON/ADEM/CRION	Oligodendrocytes - MOG	Extra	β strand/CC’-loop (P42)	FG-loop (H103/S104)	1 (N60^a)	Sera	Subcloning/cell-bound reactivity assay	Mayer et al. [56]
	NMO	Astrocytes - AQP4 isoform M23	Extra	Loop A (aa61-64)	Loop C (aa146-150) Loop E (W227)	2	Sera	Subcloning/ICC	Pisani et al. [62]
			Intra	aa1-22, Loop B (aa88-113), aa252-275	–		Sera	ELISA	Kampylafka et al. [61]
			Extra	Loop A (aa66-69)	Loop C (N153), Loop E (H230)		Sera/CSF	Cell-based assay	Tuller et al. [65]
PNS	MG	Muscle - AChR	Extra	α1 subunit (aa67-76)	–	1	Sera	Solid-phase radioimmunoassay	Tzartos et al. [33]
			Extra	α1 subunit (aa1-14, aa67-76)	–		Sera	Radioimmunoassay	Luo et al. [79]
			Extra	α1 subunit (N68, D71)	–		Sera	Peptide competition binding assay	Papadouli et al. [80] Wahlsten et al. [81]
			Intra	–	α1 subunit (aa373–380), β1 subunit (aa354–359)		Sera	Competition assay	Tzartos et al. [82]
	MG	Muscle - MuSK	Extra	Ig-like domain 1	Ig-like domain 2, Ig-like domain 3/ Fz-like domain	2	Sera	Radioimmunoprecipitation assay	McConville et al. [84]
			Extra	Ig-like domain 1, Ig-like domain 2	–		Sera	Radioimmunoprecipitation assay	Ohta et al. [85]
			Extra	Ig-like domain 1	Ig-like domain 2		Sera	Competition binding, ELISA, subcloning/ICC	Huijbers et al. [83]
			Extra	Ig-like domain 1	Ig-like domain 2, Fz-like domain		Sera	ELISA	Huijbers et al. [34]
	MG	Titin	Intra	Ig C2-like domain, Fn-like domain (MGT30)	–	0	Sera	cDNA expression library	Gautel et al. [88]
	LEMS	Neuronal P/Q-type VGCC	Extra	α1 subunit (linker region of S5-6 in repeated domains II, III, IV)	β1 subunit	1	Sera	Radioimmunoprecipitation assay	Parsons et al. [94]
			Extra	α1 subunit (linker region of domain IV)	α1 subunit (linker region of domain II)		Sera	Immunoprecipitation assay	Takamori et al. [95]
			Extra	α1 subunit (linker region of domain III)	–		Sera	Immunoblot	Iwasa et al. [96]
	NMT	Neuronal Caspr2	Extra	Disc domain	Lam1, Lam2, Egf1	12	Sera	Subcloning/ICC, Western blot	Olsen et al. [37]
	NMT	Neuronal Caspr2	Extra	Disc, Lam1 domains	–	12	Sera/CSF	Flow cytometry cell-based assay	Pinatel et al. [38]
	NPSLE	Neuronal NMDAR	Extra	GluN1/NR1 (aa19-44, aa56-81)	–	10	Sera/CSF	ELISA	Ogawa et al. [72]
	CIDP, GBS, AMAN, AIPD	Neuronal NF186	Extra	Fn V domain, Mucin-like domain	–	8	Sera	Cell-based assay	Ng et al. [107]
	CIDP, GBS, AMAN, AIPD	Glial NF155	Extra	Fn III domain, Fn IV domain	–	8	Sera	Cell-based assay	Ng et al. [107]
	CIDP, GBS	Neuronal Contactin	Extra	Ig C2-like domain V^b	–	9	Sera	Subcloning/ICC	Labasque et al. [108]

AChR acetylcholine receptor, AIPD acute inflammatory demyelinating polyradiculoneuropathy, AMAN acute motor axonal neuropathy, AMPAR α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, ADEM acute disseminated encephalomyelitis, AQP4 aquaporin-4, BON bilateral optic neuritis, Caspr2 contactin-associated protein-like 2, CIDP chronic inflammatory demyelinating polyneuropathy, CNS central nervous system, CRION chronic relapsing inflammatory optic neuropathy, CSF cerebrospinal fluid, DNA deoxyribonucleic acid, ELISA enzyme-linked immunosorbent assay, Fn fibronectin-type III, Fz Frizzled, GAD65 65 kDa glutamic acid decarboxylase, GBS Guillain-Barre syndrome, ICC immunocytochemistry, Ig immunoglobulin, LBD ligand binding domain, LEMS Lambert-Eaton myasthenic Syndrome, Lgi1 leucine-rich glioma-inactivated protein 1, MG myasthenia gravis, MOG myelin oligodendrocyte glycoprotein, MS multiple sclerosis, MuSK muscle-specific kinase, NF neurofascin, NMDAR N-methyl-D-aspartate receptor, NMO neuromyelitis optica, NMOSD neuromyelitis optica syndrome disorder, NMT acquired neuromyotonia, NPSLE neuropsychiatric systematic lupus erythematosus, PNS peripheral nervous system, SPS Stiff Person Syndrome, T1D type 1 Diabetes, VGCC voltage-gated calcium channel, VGKC voltage-gated potassium channel, - not applicable
^aPotentially important glycosylation site involved in antibody binding and formation of epitope
^bN-glycosylation sites N467/N473/N494 involved in antibody binding

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ISSN: 1742-2094

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