EUROIMMUN AG · Seekamp 31 · 23560 Lübeck (Germany) · Tel +49 451/ 58 55-0 · Fax 58 55-591 · info@euroimmun.de · www.euroimmun.com Autoantibodies in neurological diseases Cerebellum Intestine Hippocampus HEp-2 cells Cerebellum Intestine Hippocampus HEp-2 cells Hippocampus Control transfection Cerebellum Cerebellum Optic nerve Control transfection Anti-Hu positive Anti-NMDA-receptor positive Anti-Yo positive Anti-aquaporin-4 positive NMDAR (transf. cells) AQP-4 (transf. cells) Examples of relevant target antigens EUROLINE Indirect immunofluorescence GM3 G GM1 G GM2 G GQ1b G GT1b G GD1a G GD1b G Control C PNMA2 P Ma2/Ta) (M Amphiphysin A CV2 C Hu H Ri R Yo Y Control C PNMA2 P Ma2/Ta) (M Amphiphysin A CV2 C Hu H Ri R Yo Y Control C T r (DNER) T Recoverin R SOX1 S Titin T Zic4 Z GAD65 GAD65 G G Hu, Ri, Yo, T r CV2 Ma/Ta Amphiphysin SOX1 Zic4 ITPR1 CARP GAD Recoverin Titin Gangliosides MAG Myelin Aquaporin-4 MOG VGKC (LGI1 + CASPR2) NMDA receptors AMPA receptors GABAB receptors DPPX IgLON5 Glycine receptors AChR
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Autoantibodies in neurological diseases - EUROIMMUN in neurological diseases ... Golgi apparatus, cytoplasmic membrane) ... moleculare of the hippocampus (neuropil staining)
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IIFT: Granular fl uorescence of almost all neuronal nuclei on the substrates cerebellum and hippocampus. The cell nuclei of the plexus myentericus (intestinal tissue) are also positive.
EUROLINE: Positive reaction of the recombinant Hu antigen (HuD).
Anti-Ri (ANNA-2*)
Autoantibodies against neuronal cell nuclei of the central nervous system (CNS)
Associated tumours: small-cell lung carcinoma, breast carcinoma
IIFT: Granular fl uorescence of almost all neuronal nuclei on the substrates cerebellum and hippocampus. The substrate intestine (plexus myentericus) shows no reac-tion.
EUROLINE: Positive reaction of the recombinant Ri anti-gen (NOVA1***).
Anti-Yo (PCA-1**)
Autoantibodies against antigens in the cytoplasm (rough ER, Golgi apparatus, cytoplasmic membrane) of the cerebellar Purkinje cells
Associated disease: cerebellar degeneration
Associated tumours: ovarian carcinoma, breast carcinoma, uterine carcinoma
IIFT: Cytoplasmic fl uorescence of the Purkinje cells on the substrate cerebellum and of individual cells in the hilus of the hippocampus. The substrate intestine (plexus myentericus) shows no specifi c reaction.
Monospecifi c test using Yo/CDR2-transfected HEK**** cells
EUROLINE: Positive reaction of the recombinant Yo antigen (CDR62*****).
Associated tumours: breast carcinoma, small-cell lung carcinoma
IIFT: Fluorescence of the presynaptic nerve ends in the cerebellum. The nerve dendrites of the stratum moleculare show a more intense fl uorescence than the stratum granulosum. The fl uorescence pattern of the stratum granulosum resembles the pattern found with antibodies against GAD.
EUROLINE: Positive reaction of the specifi c target antigen amphiphysin.
Anti-GAD
Autoantibodies against the enzyme glutamic acid decarboxylase
IIFT: Patchy fl uorescence of the stratum granulosum on the substrates cerebellum and hippocampus. Fluorescence of the pancreas islets on the substrate pancreas.
Monospecifi c test using GAD-transfected HEK cells.
EUROLINE: Monospecifi c test using purifi ed GAD.
Cerebellum
Cerebellum
Cerebellum Pancreas
GAD (transf. cells)
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Autoantibodies IIFT pattern Test systems
Anti-ZIC4
Autoantibodies against zinc fi nger proteins (probably ZIC1, 2 and 4)
Associated disease: cerebellar degeneration
Associated tumour: small-cell lung carcinoma
IIFT: ANA-like fl uorescence of the neuronal nuclei of the cerebellar stratum granulosum. The cell nuclei of the Purkinje cells are negative in the presence of anti-ZIC4 antibodies, whereas with ANA* all cells are stained. Antibodies against ZIC4 should be assessed not only on cerebellar sections, but also on transfected cells in parallel.
EUROLINE: Positive reaction of the specifi c targetantigen ZIC4.
Anti-MAG
Autoantibodies against myelin-associated glycoprotein, a cell membrane protein of the myelin sheaths
Associated diseases: paraproteinaemic neuropathy, particularly in the context of monoclonal IgM gammopathy, e.g. monoclonal gammopathy of undetermined signifi cance (MGUS) and Waldenström‘s syndrome
IIFT: Fluorescence of the lamina alba in the cerebellum. Annular fl uorescence on the substrate peripheral nerve.
Clinically relevant antibodies are mainly those of class IgM.
Anti-myelin
Autoantibodies against myelin and myelin proteins (e.g. MBP**) in the myelin sheath of axons
Associated diseases: diagnostic signifi cance is controversial
IIFT: Fluorescence of the lamina alba in the cerebellum. Fluo rescing hyaline cylinders on the substrate peripheral nerve.
Cerebellum Nerve (section)
Cerebellum ZIC4 (transf. cells)
Cerebellum Nerve (section)
*ANA = anti-nuclear antibodies **MBP = myelin basic protein
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Autoantibodies IIFT pattern Test systems
Anti-AQP-4 (NMO-IgG)
Autoantibodies against aquaporin-4 (AQP-4), a water channel of the dystroglycan protein complex
Associated diseases: neuromyelitis optica (NMO, opticospinal encephalomyelitis, Devic‘s syndrome), longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rec. ON). NMO, LETM and rec. ON can also occur with systemic lupus erythematosus or Sjögren‘s syndrome
IIFT: Perivascular fl uorescence with linear staining along the Virchow-Robin spaces and the microvessels in the grey and white matter on the substrate cerebellum, as well as a reticular fl uorescence on the substrate optic nerve.
Monospecifi c test using AQP4-transfected HEK cells.
IIFT: Fluorescence of the stratum moleculare of the hippocampus (neuropil staining) and the stratum granulosum of the cerebellum.
Monospecifi c test using NMDA receptor (NR1)-transfected HEK cells.
Optic nerve AQP-4 (transf. cells)
Cerebellum
MOG (transf. cells)Cerebellum
Hippocampus NMDAR (transf. cells)
Cerebellum
*NMDA = N-methyl-D-aspartate
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Autoantibodies IIFT pattern Test systems
Anti-AMPA receptors
Autoantibodies against glutamate receptors (type AMPA*)
Associated disease: limbic encephalitis (~ 70 % as paraneoplastic syndrome)
Associated tumours: lung carcinoma, breast carcinoma, malignant thymoma
IIFT: Fluorescence of the stratum moleculare of the hippocampus (neuropil staining), the stratum moleculare and stratum granulosum of the cerebellum and the Purkinje cells.
Monospecifi c test using AMPA1/2-transfected HEK cells.
Anti-GABAB receptors
Autoantibodies againstGABAB
** receptors
Associated disease: limbic encephalitis (~ 50 % as paraneoplastic syndrome)
Associated tumour: small-cell lung carcinoma
IIFT: Coarse granular fl uorescence of the stratum moleculare of the hippocampus (neuropil staining) and the cerebellum. Also patchy fl uorescence of the cerebellar stratum granulosum.
Monospecifi c test using GABAB receptor-transfected HEK cells.
Anti-LGI1
Autoantibodies against LGI1***, a protein associated with voltage-gated potassium channels (VGKC)
IIFT: Fine granular fl uorescence of the stratum moleculare of the hippocampus (neuropil staining) and the cerebellum. Also patchy fl uorescence of the cerebellar stratum granulosum. The outer molecular layer of the hippocampus shows a stronger reaction than the inner layer.
Monospecifi c test using LGI1-transfected HEK cells.
IIFT: Fluorescence of the stratum moleculare of the hippocampus (neuropil staining) and the cerebellum. Also patchy fl uorescence of the cerebellar stratum granulosum.
Monospecifi c test using CASPR2-transfected HEK cells.
Anti-DPPX
Autoantibodies against the regulatory subunit of the voltage-gated potassium channel Kv4.2
Associated disease: encephalomyelitis
IIFT: Positive reaction of the stratum granulosum and stratum moleculare of the cerebellum as well as the stratum lucidum of the hippocampus.
Monospecifi c test using DPPX**-transfected HEK cells.
Anti-IgLON5
Autoantibodies against a neuronal cell adhesion protein of the Ig superfamily
Associated diseases: parasomnia, tauopathy
IIFT: Fluorescence of the stratum moleculare of the hippocampus (neuropil staining) and the cerebellum. In addition, patchy fl uorescence of the cerebellar stratum granulosum.
Monospecifi c test using IgLON5-transfected HEK cells.
*CASPR2 = contactin-associated protein 2 **DPPX = dipeptidyl aminopeptidase-like protein 6
CASPR2 (transf. cells)
Cerebellum
Hippocampus
DPPX (transf. cells)Hippocampus
Cerebellum
Cerebellum
Hippocampus
IgLON5 (transf. cells)
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Antibodies (synonym) Antigen
(molecular weight)
Sample
material
Syndrome Most frequent tumours
Antibodies in diseases of the central nervous system
Anti-Hu (ANNA-1) Hu protein (38 kDa) Serum Encephalomyelitis,sensory neuropathy
SCLC, neuroblastoma
Anti-Ri (ANNA-2) NOVA (55 kDa and 80 kDa) Serum Opsoclonus myoclonussyndrome
Breast carcinoma, SCLC
Anti-Yo (PCA-1) CDR2, CDR62 (34 kDa and 62 kDa)
Serum Cerebellar degeneration Ovarian, breast and uterine carcinoma
PCA-2 Purkinje cell protein (280 kDa) Serum Encephalitis,neuropathy
SCLC
Anti-PNMA1 (Ma1) Ma protein (37 kDa) Serum Rhombencephalitis (brainstem), limbic encephalitis
Breast carcinoma, varioustumours
Anti-PNMA2 (Ma2/Ta) Ma protein (40 kDa) Serum Rhombencephalitis (brainstem), limbic encephalitis
Testicular carcinoma
Anti-Tr (DNER) Purkinje cell protein Serum Cerebellar degeneration Hodgkin‘s lymphoma