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Autoantibodies in Neurological Diseases

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Autoantibodies in Neurological Diseases Autoantibodies in neurological diseases Hu, Ri, Yo, Tr CV2 Amphiphysin Amphiphysin GM1 Ma/Ta CV2 Amphiphysin Cerebellum Intestine Hippocampus Control transfection CV2 GM2 SOX1 PNMAP 2 (MMa2/Ta) Zic4 PNMP A2 GM3G ITPR1 (MMa2/Ta) RiR CARP YoY RiR GD1G a GAD Hippocampus HEp-2 cells Cerebellum NMDAR (transf. cells) Recoverin HuH Titin Anti-Hu positive Anti-NMDA-receptor positive YoY GD1G b Recoverin Gangliosides MAG HuH GT1b SOS X1 Myelin Aquaporin-4 Titin GQ1G b MOG Zic4 VGKC (LGI1 + CASPR2) Cerebellum Intestine Cerebellum Control transfection NMDA receptors GAD65G AMPA receptors Tr (DNER) GABAB receptors DPPX Control CoC ntrol CoC ntrol IgLON5 Hippocampus HEp-2 cells Optic nerve AQP-4 (transf. cells) Glycine receptors Anti-Yo positive Anti-aquaporin-4 positive AChR Indirect immunofl uorescence EUROLINE Examples of relevant target antigens EUROIMMUN AG · Seekamp 31 · 23560 Lübeck (Germany) · Tel +49 451/5855-0 · Fax 5855-591 · [email protected] · www.euroimmun.com 2 Autoantibodies IIFT pattern Test systems Anti-Hu (ANNA-1*) IIFT: Granular fl uorescence of almost all neuronal nuclei on the substrates cerebellum and hippocampus. The Autoantibodies against basic, RNA- cell nuclei of the plexus myentericus (intestinal tissue) binding proteins of the neuronal cell are also positive. nuclei of the central and peripheral nervous system EUROLINE: Positive reaction of the recombinant Hu antigen (HuD). Associated diseases: encephalomyelitis, subacute sensory neuronopathy (Denny-Brown syndrome), autonomous neuropathy Associated tumours: small-cell lung carcinoma, Cerebellum Intestine neuroblastoma Anti-Ri (ANNA-2*) IIFT: Granular fl uorescence of almost all neuronal nuclei on the substrates cerebellum and hippocampus. The Autoantibodies against neuronal cell substrate intestine (plexus myentericus) shows no reac- nuclei of the central nervous system tion. (CNS) EUROLINE: Positive reaction of the recombinant Ri anti- Associated disease: opsoclonus myoclonus syn- gen (NOVA1***). drome Associated tumours: small-cell lung carcinoma, breast carcinoma Cerebellum Intestine Anti-Yo (PCA-1**) IIFT: Cytoplasmic fl uorescence of the Purkinje cells on the substrate cerebellum and of individual cells in Autoantibodies against antigens the hilus of the hippocampus. The substrate intestine in the cytoplasm (rough ER, Golgi (plexus myentericus) shows no specifi c reaction. apparatus, cytoplasmic membrane) of Intestine the cerebellar Purkinje cells Monospecifi c test using Yo/CDR2-transfected HEK**** cells Associated disease: cerebellar degeneration Associated tumours: ovarian carcinoma, breast EUROLINE: Positive reaction of the recombinant Yo carcinoma, uterine carcinoma antigen (CDR62*****). Cerebellum Yo (transf. cells) *ANNA = anti-neuronal nuclear antibodies **PCA = Purkinje cell autoantibodies ***NOVA = neuronal onconeural ventral nervous system antigen ****HEK = human embryonic kidney ***** CDR = cerebellar degeneration-related antigen 3 Autoantibodies IIFT pattern Test systems PCA-2* IIFT: Fluorescence of the cytoplasm of the cerebellar Purkinje cells, which extends into the dendrites. Autoantibodies against a 280 kDa protein of the cerebellar Purkinje cells Associated diseases: limbic/brain stem encephalitis, cerebellar ataxia, Lambert-Eaton myasthenic syndrome (LEMS), autonomous neuropathy, motor neuropathy Associated tumours: gynaecological tumours, small- cell lung carcinoma Cerebellum Anti-Tr Coarse granular fl uorescence of the cytoplasm of the cerebellar Purkinje cells, dot-like staining of the Autoantibodies against DNER** protein molecular layer. in the Purkinje cells of the cerebellum Monospecifi c test using DNER-transfected HEK cells. Associated disease: cerebellar degeneration Associated tumour: Hodgkin‘s lymphoma EUROLINE: Positive reaction of the specifi c target antigen Tr (DNER). Cerebellum DNER (transf. cells) Anti-CARP (anti-carbonic anhydrase- IIFT: The molecular layer and the cytoplasm of the related protein VIII) Purkinje cells in the cerebellum show a dotted to fi ne- speckled pattern. Autoantibodies against CARP VIII in the Purkinje cell layer of the Monospecifi c test using CARP VIII-transfected HEK cells. cerebellum Associated diseases: paraneoplastic cerebellar degeneration, cerebellar ataxia Associated tumours: melanoma, ovarian carcinoma Cerebellum CARP (transf. cells) *PCA = Purkinje cell autoantibodies **DNER = delta/notch-like epidermal growth factor-related receptor 4 Autoantibodies IIFT pattern Test systems Anti-ITPR1 (Anti-Sj) IIFT: The molecular layer and the cytoplasm of the (anti-Sj / inositol 1,4,5-trisphosphate Purkinje cells in the cerebellum show a dotted to fi ne- receptor) speckled pattern. Autoantibodies against ITPR1 in Monospecifi c test using ITPR1-transfected HEK cells. Purkinje cells of the cerebellum Associated disease: cerebellar ataxia Associated tumour: NSCLC in an unpublished case Cerebellum ITPR1 (transf. cells) Anti-glia nuclear antibodies (AGNA) IIFT: Fluorescence of the cell nuclei of the Bergmann glia in the Purkinje cell layer of the cerebellum. Possible antigen: SOX1 Associated diseases: paraneoplastic Lambert- Eaton myasthenic syndrome (LEMS), cerebellar degeneration, sensory neuropathy Associated tumour: small-cell lung carcinoma Cerebellum Anti-Ma (Ma1, Ma2/Ta) IIFT: Reaction of the nerve cell nucleoli on the substrates cerebellum, cerebrum and hippocampus. Autoantibodies against Ma1 (PNMA1*; 37 kDa) and Ma2/Ta (PNMA2*; 40 kDa), EUROLINE: Anti-Ma (Ma1 and Ma2/Ta) antibodies proteins in the nucleoli of the neuronal produce a positive reaction with the recombinant Ma2/ cell nuclei Ta (PNMA2*) antigen. Associated diseases: brain stem encephalitis, limbic encephalitis Associated tumours: lung carcinoma, testicular carcinoma (esp. Ma2/Ta), breast carcinoma Cerebellum Cerebrum PNMA1/2 = paraneoplastic antigen Ma1/2 5 Autoantibodies IIFT pattern Test systems Anti-CV2 IIFT: Sand-like fl uorescence on the substrate cerebellum, most visible in the stratum moleculare. Autoantibodies against CV2, a 66-kDa protein EUROLINE: Positive reaction of the recombinant CV2. Associated diseases: sensory and autonomous neuropathy, encephalitis, extrapyramidal motor syndrome, cerebellar degeneration Associated tumours: small-cell lung carcinoma, thymoma Cerebellum Anti-amphiphysin IIFT: Fluorescence of the presynaptic nerve ends in the cerebellum. The nerve dendrites of the stratum Autoantibodies against amphiphysin, moleculare show a more intense fl uorescence than the a synaptic protein with a molecular stratum granulosum. The fl uorescence pattern of the weight of 128 kDa stratum granulosum resembles the pattern found with antibodies against GAD. Associated disease: paraneoplastic stiff-person syndrome EUROLINE: Positive reaction of the specifi c target Associated tumours: breast carcinoma, small-cell antigen amphiphysin. lung carcinoma Cerebellum Anti-GAD IIFT: Patchy fl uorescence of the stratum granulosum on the substrates cerebellum and hippocampus. Autoantibodies against the enzyme Fluorescence of the pancreas islets on the substrate glutamic acid decarboxylase pancreas. GAD (transf. cells) Associated diseases: stiff-person syndrome, limbic Monospecifi c test using GAD-transfected HEK cells. encephalitis EUROLINE: Monospecifi c test using purifi ed GAD. Cerebellum Pancreas 6 Autoantibodies IIFT pattern Test systems Anti-ZIC4 IIFT: ANA-like fl uorescence of the neuronal nuclei of the cerebellar stratum granulosum. The cell nuclei of the Autoantibodies against zinc fi nger Purkinje cells are negative in the presence of anti-ZIC4 proteins antibodies, whereas with ANA* all cells are stained. (probably ZIC1, 2 and 4) Antibodies against ZIC4 should be assessed not only on cerebellar sections, but also on transfected cells in Associated disease: cerebellar degeneration parallel. Associated tumour: small-cell lung carcinoma EUROLINE: Positive reaction of the specifi c target antigen ZIC4. Cerebellum ZIC4 (transf. cells) Anti-MAG IIFT: Fluorescence of the lamina alba in the cerebellum. Annular fl uorescence on the substrate peripheral nerve. Autoantibodies against myelin- associated glycoprotein, a cell Clinically relevant antibodies are mainly those of class membrane protein of the myelin IgM. 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 Cerebellum Nerve (section) Anti-myelin IIFT: Fluorescence of the lamina alba in the cerebellum. Fluo rescing hyaline cylinders on the substrate Autoantibodies against myelin and peripheral nerve. myelin proteins (e.g. MBP**) in the myelin sheath of axons Associated diseases: diagnostic signifi cance is controversial Cerebellum Nerve (section) *ANA = anti-nuclear antibodies **MBP = myelin basic protein 7 Autoantibodies IIFT pattern Test systems Anti-AQP-4 (NMO-IgG) IIFT: Perivascular fl uorescence with linear staining along the Virchow-Robin spaces and the microvessels Autoantibodies against aquaporin-4 in the grey and white matter on the substrate (AQP-4), a water channel of the cerebellum, as well as a reticular fl uorescence on the dystroglycan protein complex Cerebellum substrate optic nerve. Associated diseases: neuromyelitis optica (NMO, Monospecifi c test using AQP4-transfected HEK cells. 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 Optic nerve
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