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Identification of the flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis
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نویسنده
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hahn s. ,trendelenburg g. ,scharf m. ,denno y. ,brakopp s. ,teegen b. ,probst c. ,wandinger k.p. ,buttmann m. ,haarmann a. ,szabados f. ,vom dahl m. ,kümpfel t. ,eichhorn p. ,gold h. ,paul f. ,jarius s. ,melzer n. ,stöcker w. ,komorowski l.
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منبع
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journal of neuroinflammation - 2017 - دوره : 14 - شماره : 1
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چکیده
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Background: autoantibodies,in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (mog),aid as biomarkers in the differential diagnosis of demyelination. here,we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (ms). methods: the target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in hek293 cells. results: serum and csf of the index patient produced a fine-granular igg indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. flotillin-1 and flotillin-2 were identified as target autoantigens. they also reacted with recombinant human flotillin-1/2 co-expressed in hek293 cells,but not with the individual flotillins in fixed- and live-cell assays. moreover,neutralization using flotillin-1/2,but not the single flotillins,abolished the tissue reactivity of patient serum. screening of 521 patients,for whom anti-aquaporin-4 testing was requested and negative,revealed 8 additional patients with anti-flotillin-1/2 autoantibodies. all eight were negative for anti-mog. six patients ex post fulfilled the revised mcdonald criteria for ms. vice versa,screening of 538 ms sera revealed anti-flotillin-1/2 autoantibodies in eight patients. the autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. conclusions: autoantibodies against the flotillin-1/2 heterocomplex,a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve,are present in 1-2% of patients with bona fide ms. © 2017 the author(s).
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کلیدواژه
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Autoantibodies; Flotillin; Histo-immunoprecipitation; Multiple sclerosis; Optic neuritis; Reggie
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آدرس
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euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560, Germany, university medical center göttingen,department of neurology,göttingen, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560,germany,clinical immunological laboratory prof. dr. med stöcker,lübeck, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560, Germany, university medical center schleswig holstein (uksh),department of neurology,lübeck, Germany, university of würzburg,department of neurology,würzburg,germany,caritas hospital,department of neurology,bad mergentheim, Germany, university of würzburg,department of neurology,würzburg, Germany, medical laboratory osnabrück,georgsmarienhütte, Germany, ammerland klinik,department of neurology,westerstede, Germany, ludwig maximilian university,institute of clinical neuroimmunology,munich, Germany, ludwig maximilian university,institute of clinical chemistry,munich, Germany, klinikum am gesundbrunnen,department of neurology,heilbronn, Germany, charité universitätsmedizin,neurocure clinical research center and clinical and experimental multiple sclerosis research center,department of neurology,berlin,germany,experimental and clinical research center,max delbrück center for molecular medicine and charité universitätsmedizin,berlin, Germany, university of heidelberg,department of neurology,heidelberg, Germany, university of münster,department of neurology,münster, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560,germany,clinical immunological laboratory prof. dr. med stöcker,lübeck, Germany, euroimmun ag,institute of experimental immunology,seekamp 31,lübeck,23560, Germany
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Authors
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