Startpage Heidelberg University Hospital Startpage Heidelberg University Hospital
Department of… Research Neuroimmunology Molecular… Paraneoplastic and…

PARANEOPLASTIC AND OTHER AUTOANTIBODY-RELATED DISORDERS

Diagnostic und pathophysiological relevance of autoantibodies in neurological disorders (other than NMO and MOG-EM)


Principal investigators: Sven Jarius, Brigitte Wildemann
 

This project focuses on the diagnostic and pathophysiological relevance of autoantibodies and B cells in disorders of the central and/or peripheral nervous system (e.g., paraneoplastic and idiopathic cerebellar ataxia, limbic encephalitis, peripheral neuropathy, Susac syndrome, multiple sclerosis).
 

An independent project is dedicated to investigating the role of antibodies to aquaporin-4 (NMO-IgG/AQP4-IgG) in patients with neuromyelitis optica (NMO) and related syndromes (see here) and of antibodies to myelin oligodendrocyte glycoprotein (MOG) in demyelinating diseases of the CNS (see here).

 

Email:
sven.jarius(at)med.uni-heidelberg.de

brigitte.wildemann(at)med.uni-heidelberg.de

Selected publications

  • Höltje M, Mertens R, Schou MB, Saether SG, Kochova E, Jarius S, Prüss H, Komorowski L, Probst C, Paul F, Bellmann-Strobl J, Gitler D, Benfenati F, Piepgras J, Ahnert-Hilger G, Ruprecht K. Synapsin-antibodies in psychiatric and neurological disorders: prevalence and clinical findings. Brain, Behaviour, and Immunity 2017; in press.
  • Wallwitz U, Brock S, Schunck A, Wildemann B, Jarius S, Hoffmann F. From dizziness to severe ataxia and dysarthria: New cases of anti-Ca/ARHGAP26 autoantibody-associated cerebellar ataxia suggest a broad clinical spectrum. J Neuroimmunol. 2017 Aug 15;309:77-81.
  • Lewerenz J, Jarius S, Wildemann B, Wandinger KP, Leypoldt F. [Autoantibody-associated autoimmune encephalitis and cerebellitis: Clinical presentation, diagnostic work-up and treatment]. Nervenarzt 2016 Dec;87(12):1293-1299.
  • Jarius S, Ringelstein M, Haas J, Serysheva II, Komorowski L, Fechner K, Wandinger KP, Albrecht P, Hefter H, Moser A, Neuen-Jacob E, Hartung HP, Wildemann B, Aktas O. Inositol 1,4,5-trisphosphate receptor type 1 autoantibodies in paraneoplastic and non-paraneoplastic peripheral neuropathy. J Neuroinflammation 2016; 13:278.
  • Kleffner I, Dörr J, Ringelstein M, Groß C, Böckenfeld Y, Schwindt W, Sundermann B, Lohmann H, Wersching H, Promesberger J, von Königsmarck N, Alex A, Guthoff R, Frijns CJM, Kappelle JL, Jarius S, Wildemann B, Aktas O, Paul F, Wiendl H, Duning H; for the European Susac Consortium (EuSaC). Diagnostic criteria for Susac Syndrome. JNNP 2016 Dec;87(12):1287-1295.
  • Stich O, Perera S, Berger B, Jarius S, Wildemann B, Baumgartner A, Rauer S. Prevalence of neurofascin-155 antibodies in patients with multiple sclerosis. J Neurol Sci 2016 May 15;364:29-32.
  • Jarius S, Metz I, König F, Ruprecht K, Reindl M, Paul F, Brück W, Wildemann B. Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in ‘pattern II multiple sclerosis’ and brain biopsy findings in a MOG-IgG-positive case. Mult Scler 2016 Oct;22(12):1541-1549.
  • Baron R, Ferriero D, Frisoni G, Bettegowda C, Gokaslan Z, Kessler J, Vezzani A, Waxman S, Weller M, Jarius S, Wildemann B. Neurology-the next 10 years. Nature Rev Neurol 2015; Nov;11(11):658-64. Epub 2015 Oct 27.
  • Jarius S, Wildemann B. ‘Medusa head ataxia’: The expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1, anti-CARP VIII. J Neuroinflammation 2015; 12:166. FREE PDF
  • Jarius S, Wildemann B. ‘Medusa head ataxia’: The expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26, anti-VGCC. J Neuroinflammation 2015; 12:167. FREE PDF
  • Jarius S, Wildemann B. ‘Medusa head ataxia’: The expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, Anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook. J Neuroinflammation 2015; 12:168. FREE PDF
  • Jarius S, Wildemann B, Stöcker W, Moser A, Wandinger KP. Psychotic syndrome associated with antibodies to ARHGAP26 (anti-Ca) and voltage-gated potassium channels. J Neuroimmunol 2015 Sep 8; 286:79-82. Epub 2015 Jul 22.
  • Piepgras J, Hoeltje M, Michel K, Li Q, Otto C, Drenckhahn C, Probst C, Schemann M, Jarius S, Stöcker W, Balint B, Meinck HM, Buchert R, Dalmau JO, Ahnert-Hilger G, Ruprecht K. Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons. Neurology 2015 Sep 8;85(10):890-7. Epub 2015 Aug 19.
  • Ringelstein M, Albrecht P, Kleffner I, Bühn B, Harmel J, Müller AK, Finis D, Guthoff R, Bergholz R, Duning T, Krämer M, Paul F, Brandt F, Oberwahrenbrock T, Mikolajczak J, Wildemann B, Jarius S, Hartung HP, Aktas O, Dörr J. Retinal pathology in Susac syndrome detected by spectral-domain optical coherence tomography. Neurology 2015 Aug 18;85(7):610-8. Epub 2015 Jul 22.
  • Probst C, Komorowski L, de Graaff E, van Coevorden-Hameete M, Rogemond V, Honnorat J, Sabeter L, Graus F, Jarius S, Voltz R, Wildemann B, Franciotta D, Blöcker I, Schlumberger W, Stöcker W, Sillevis Smitt PAE. Standardized test for anti-Tr/DNER in patients with paraneoplastic cerebellar degeneration. Neurology: Neuroimmunology & Neuroinflammation 2015 Feb 26;2(2):e68.
  • Jarius S, Scharf M, Begemann N, Stöcker W, Probst C, Serysheva II, Nagel S, Graus F, Psimaras D, Wildemann B*, Komorowski L*. Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia. J Neuroinflammation 2014; 11:206.
  • Stoeck K, Carstens PO, Jarius S, Raddatz D, Stöcker W, Wildemann B, Schmidt J. Prednisolone and azathioprine are effective in DPPX antibody-positive autoimmune encephalitis. Neurology: Neuroimmunology & Neuroinflammation. 2015 Jun; 2(3): e86. Epub 2015 Mar 12.
  • Fidzinski P, Jarius S, Gaebler C, Boegner F, Nohr R, Ruprecht K. Faciobrachial dystonic seizures and antibodies to Lgi1 in a 92-year-old patient: A case report. J Neurol Sci 2014 Oct 22;347(1-2):404-405. Epub 2014 Oct 22.
  • Jarius S, Kleffner I, Dörr JM, Sastre-Garriga J, Illes Z, Eggenberger E, Chalk C, Ringelstein M, Aktas O, Montalban X, Fechner K, Stöcker W, Ringelstein EB, Paul F, Wildemann B. Clinical, paraclinical and serological findings in Susac syndrome: an international multi-centre study. J Neuroinflammation 2014 Mar 8; 11:46.
  • Balint B, Jarius S, Nagel S, Haberkorn U, Probst C, Blöcker IM, Bahtz R, Komorowski L, Stöcker W, Kastrup A, Kuthe M, Meinck HM. Progressive encephalomyelitis with rigidity and myoclonus: A new variant with DPPX antibodies.Neurology 2014 Apr 29;82(17):1521-8. Epub 2014 Apr 2.
  • Doss S, Nümann A, Ziegler A, Siebert E, Borowski K, Stöcker W, Prüss H, Wildemann B, Endres M, Jarius S. Anti-Ca/anti-ARHGAP26 antibodies associated with cerebellar atrophy and cognitive decline. J Neuroimmunol 2014 Feb 15;267(1-2):102-4. Epub 2013 Nov 6.
  • Dörr J, Krautwald S, Wildemann B, Jarius S, Ringelstein M, Duning T, Aktas O, Ringelstein EB, Paul F, Kleffner I. Characteristics of Susac syndrome: a review of all reported cases. Nature Rev Neurol 2013 Jun;9(6):307-16.
  • Mundiyanapurath S, Jarius S, Probst C, Stöcker W, Wildemann B, Bösel J. GABA-B-receptor antibodies in paraneoplastic brainstem encephalitis. J Neuroimmunol 2013 Jun 15;259(1-2):88-91. Epub 2013 Apr 28.
  • Wildemann B, Bien CG. [Immune-mediated encephalomyelitis]. Nervenarzt. 2013 Apr;84(4):435.
  • Balint B, Regula JU, Jarius S, Wildemann B. Caspr2-antibodies in limbic encephalitis with cerebellar ataxia, dyskinesias and myoclonus. J Neurol Sci 2013 Apr 15;327(1-2):73-4. Epub 2013 Mar 5.
  • Jarius S, Steinmeyer F, Knobel A, Streitberger K, Hotter B, Horn S, Heuer H, Schreiber SJ, Wilhelm T, Trefzer U, Wildemann B, Ruprecht K. GABAB receptor antibodies in paraneoplastic cerebellar ataxia. J Neuroimmunol 2013 Mar 15;256(1-2):94-6. Epub 2013 Jan 14.
  • Jarius S, Martínez-García P, Hernandez AL, Brase JC, Borowski K, Regula JU, Meinck HM, Stöcker W, Wildemann B, Wandinger KP. Two new cases of anti-Ca (anti-ARHGAP26/GRAF) autoantibody-associated cerebellar ataxia. J Neuroinflammation 2013 Jan 15;10:7.
  • Wildemann B, Jarius S. The expanding range of autoimmune disorders of the nervous system. Lancet Neurol 2013 Jan;12(1):22-4.
  • Kraus PD, Wolff D, Grauer O, Angstwurm K, Jarius S, Wandinger KP, Holler E, Schulte-Mattler W, Kleiter I. Muscle Cramps and Neuropathies in Patients with Allogeneic Hematopoietic Stem Cell Transplantation and Graft-versus-Host Disease. PLoS ONE 2012; 7(9): e44922. Epub 2012 Sep 17.
  • Harrer A, Tumani H, Niendorf S, Lauda F, Geis C, Weishaupt A, Kleinschnitz C, Rauer S, Kuhle J, Stangel M, Weber F, Uhr M, Linnebank M, Wildemann B, Jarius S, Guger M, Ayzenberg I, Chan A, Zettl U, Wiendl H, Pilz G, Hitzl W, Weber JR, Kraus J. Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy. Mult Scler 2013 Aug;19(9):1209-1212. Epub 2012 Oct 23.
  • Jarius S, Eichhorn P, Wildemann B, Wick M. Usefulness of antibody index assessment in cerebrospinal fluid from patients negative for total-IgG oligoclonal bands. Fluids and barrieres of the CNS 2012; 9:14. Epub 2012 July 31.
  • Elliott C, Lindner M, Arthur A, Brennan K, Jarius S, Hussey J, Chan A, Stroet A, Tomas Olsson, Willison H, Barnett SC, Meinl E, Linington C. Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis. Brain 2012 Jun;135(Pt 6):1819-33. Epub 2012 May 4.
  • Wuerfel J, Sinnecker T, Ringelstein EB, Jarius S, Schwindt W, Niendorf T, Paul F, Kleffner I, Dörr J. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler 2012 Nov;18(11):1592-9. Epub 2012 Jun 18.
  • Haas J, Bekeredjian-Ding I, Milkova M, Balint B, Schwarz A, Korporal M, Jarius S, Fritz B, Lorenz HM, Wildemann B. B cells undergo unique compartmentalized redistribution in multiple sclerosis. J Autoimmun 2011; Dec;37(4):289-99. Epub 2011 Sep 15.
  • Stich O, Klages E, Bischler P, Jarius S, Rasiah C, Voltz R, Rauer S. SOX1 antibodies in sera from patients with paraneoplastic neurological syndromes. Acta Neurol Scand 2012 May;125(5):326-31. Epub 2011 Jul 14.
  • Dörr J, Jarius S, Wildemann B, Ringelstein EB, Schwindt W, Deppe M, Wandinger KP, Promesberger J, Paul F, Kleffner I. [Susac syndrome : An interdisciplinary challenge.] Nervenarzt 2011 Oct;82(10):1250-63.
  • Piccolo G, Tavazzi E, Jarius S, Alfonsi E, Cavagna L, Piccolo L, Zardini E, Voltz R, Franciotta D. Anti-Ma2/Ta antibodies in a woman with primary lateral sclerosis-like phenotype and Sjögren syndrome. Neurol Sci 2011 Oct;32(5):915-7. Epub 2011 Mar 3.
  • Benedetti L, Zardini E, Briani C, Beronio A, Gastaldi S, Jarius S, Mancardi GL, Schenone A, Franciotta D. B-cell-activating factor in rituximab-treated patients with anti-MAG polyneuropathy. J Neurol Neurosurg Psychiatr 2010;Nov;82(11):1291-4. Epub 2010 Dec 16.
  • Jarius S, Stich O, Speck J, Rasiah Ch, Wildemann B, Meinck HM, Rauer S. Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients with stiff person syndrome. J Neuroimmunol. 2010 Dec 15;229(1-2):219-24. Epub 2010 Sep 1.
  • Franciotta D, Di Stefano AL, Jarius S, Zardini E, Tavazzi E, Ballerini C, Marchioni E, Bergamaschi R, Ceroni M. Cerebrospinal BAFF and Epstein-Barr virus-specific oligoclonal bands in multiple sclerosis and other inflammatory demyelinating neurological diseases. J Neuroimmunol. 2011 Jan;230(1-2):160-3. Epub 2010 Nov 24.
  • Jarius S, Wandinger KP, Horn S, Heuer H, Wildemann B. A new Purkinje cell antibody (anti-Ca) associated with subacute cerebellar ataxia: immunological characterization. J Neuroinflammation 2010 Mar 12;7:21.
  • Wandinger KP, Probst C, Komorowski L, Saschenbrecker S, Rosemann A, Mothes T, Zillikens D, Dalmau J, Jarius S, Schlumberger W, Stöcker W. Novel recombinant antigenic targets for the determination of (auto)antibodies in autoimmune dermatoses, neurological disorders and gastrointestinal diseases. In: K. Conrad, E.K.L. Chan, M.J. Fritzler, R.L. Humbel, P. von Landenberg, Y. Shoenfeld (Eds.) From Pathogenesis to Therapy of Autoimmune Diseases, Pabst, Lengerich, Berlin, Bremen, Miami, Riga, Viernheim, Wien, Zagreb 2009, p. 179-190.
  • Jarius S, Neumayer B, Wandinger KP, Hartmann M, Wildemann B. Anti-endothelial serum antibodies in a patient with Susac's syndrome. J Neurol Sci 2009 Oct 15;285(1-2):259-61. Epub 2009 Jul 29.
  • Jarius S, Arnold S, Linke R, Noachtar S, Schlemmer M, Issels R, Voltz R. Long term survival in anti-Hu associated adult neuroblastoma. J Neurol Sci 2009 Sep 15;284(1-2):205-8. Epub 2009 May 13.
  • Stich O, Jarius S, Rasiah C, Voltz R, Rauer S. Recombinant immunoblot for assessment of intrathecally synthesised paraneoplastic antineuronal antibodies in cerebrospinal fluid from patients with paraneoplastic neurological syndromes. Clin Chem Lab Med. 2008;46(12):1793-5.
  • Jarius S, Eichhorn P, Jacobi C, Wildemann B, Wick M, Voltz R. The intrathecal, polyspecific antiviral immune response: Specific for MS or a general marker of CNS autoimmunity? J Neurol Sci 2009 May 15;280(1-2):98-100. Epub 2008 Nov 28.
  • Franciotta D, Columba-Cabezas S, Andreoni L, Ravaglia S, Jarius S, Romagnolo S, Tavazzi E, Bergamaschi R, Zardini E, Aloisi F, Marchioni E. Oligoclonal IgG band patterns in inflammatory demyelinating human and mouse diseases. J Neuroimmunol. 2008 Aug 30;200(1-2):125-8. Epub 2008 Jul 7.
  • Jarius S, Hoffmann LA, Stich O, Clover L, Rauer S, Vincent A, Voltz R. Relative frequency of VGKC and 'classical' paraneoplastic antibodies in patients with limbic encephalitis. J Neurol 2008 Jul;255(7):1100-1. Epub 2008 Jun 27.
  • Hoffmann LA, Jarius S, Pellkofer HL, Schueller M, Krumbholz M, Koenig F, Johannis W, la Fougere C, Newman T, Vincent A, Voltz R. Anti-Ma and anti-Ta associated paraneoplastic neurological syndromes: 22 newly diagnosed patients and review of previous cases. J Neurol Neurosurg Psychiatry. 2008 Jul;79(7):767-73. Epub 2008 Jan 25.
  • Jarius S, Stich O, Rasiah C, Voltz R, Rauer S. Qualitative evidence of Ri specific IgG-synthesis in the cerebrospinal fluid from patients with paraneoplastic neurological syndromes. J Neurol Sci 2008 May 15;268(1-2):65-8. Epub 2007 Dec 21.
  • Jarius S, Hoffmann L, Clover L, Vincent A, Voltz R. CSF findings in patients with voltage gated potassium channel antibody associated limbic encephalitis. J Neurol Sci 2008 May 15;268(1-2):74-7. Epub 2008 Feb 20.
  • Poepel A, Jarius S, Heukamp LC, Urbach H, Elger CE, Bien CG, Voltz R. Neurological course of long-term surviving patients with SCLC and anti-Hu syndrome. J Neurol Sci 2007 Dec 15;263(1-2):145-8. Epub 2007 Aug 15.
  • Jarius S, Eichhorn P, Albert MH, Wagenpfeil S, Wick M, Belohradsky BH, Hohlfeld R, Jenne DE, Voltz R. Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFalpha-dependent and Fc-receptor-independent way. Blood 2007 May 15;109(10):4376-82. Epub 2007 Jan 30.
  • Stich O, Jarius S, Kleer B, Rasiah C, Voltz R, Rauer S. Specific antibody index in cerebrospinal fluid from patients with central and peripheral paraneoplastic neurological syndromes. J Neuroimmunol 2007 Feb;183(1-2):220-4. Epub 2007 Jan 16.
  • Fauser S, Talazko J, Wagner K, Ziyeh S, Jarius S, Vincent A, Schulze-Bonhage A. FDG-PET and MRI in potassium channel antibody-associated non-paraneoplastic limbic encephalitis: correlation with clinical course and neuropsychology. Acta Neurol Scand 2005 May;111(5):338-43.
  • Jarius S, Wandinger KP, Borowski K, Stoecker W, Wildemann B. Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: Case report and review of the literature. Clin Neurol Neurosurg 2012 May;114(4):331-5. Epub 2011 Dec 3.
  • Mader S, Gredler V, Schanda K, Rostasy K, Dujmovic I, Pfaller K, Lutterotti A, Jarius S, Di Pauli F, Kuenz B, Ehling R, Hegen H, Deisenhammer F, Aboul-Enein F, Storch MK, Koson P, Drulovic J, Kristoferitsch W, Berger T, Reindl M. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinfl 2011 Dec; 8:184