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Targeting B Cells in Neurological Autoimmune Diseases

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Drugs Targeting B-Cells in Autoimmune Diseases

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

As B cells are thought to play an active role in the pathophysiology of a large number of neurological disorders through the secretion of antibodies, the activation-dependent release of cytokines and the mutual activation of T cells, B-cell-directed therapy has emerged as a promising tool in the therapeutic strategies of a range of autoimmune neurological diseases, such as multiple sclerosis (MS), neuromyelitis optica, autoimmune encephalitis, chronic inflammatory demyelinating polineuropathies, myasthenia gravis, and Lambert–Eaton syndrome. Rituximab, an anti-CD20 monoclonal antibody, has been the most frequently reported therapy in this context. However, evidence of efficacy is limited to case reports or short small series, most of them retrospective, and with a few exceptions, e.g. MS, randomized controlled trials are lacking. In this article, we review and discuss the available literature on B cell-targeted therapies in autoimmune neurologic diseases.

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References

  • Alavi S, Kord Valeshabad A, Moradveisi B et al (2012) Clinical responses to rituximab in a case of neuroblastoma with refractory opsoclonus myoclonus ataxia syndrome. Case Rep Oncol Med 2012:164082. doi:10.1155/2012/164082

    PubMed  Google Scholar 

  • Archelos JJ, Storch MK, Hartung HP (2000) The role of B cells and autoantibodies in multiple sclerosis. Ann Neurol 47(6):694–706

    PubMed  CAS  Google Scholar 

  • Awad A, Stüve O, Mayo M et al (2011) Anti-glutamic acid decarboxylase antibody-associated ataxia as an extrahepatic autoimmune manifestation of hepatitis C infection: a case report. Case Rep Neurol Med 2011:975152

    PubMed  Google Scholar 

  • Bacorro EA, Tehrani R (2010) Stiff-person syndrome: persistent elevation of glutamic acid decarboxylase antibodies despite successful treatment with rituximab. J Clin Rheumatol 16(5):237–239

    PubMed  Google Scholar 

  • Baek WS, Bashey A, Sheean GL (2007) Complete remission induced by rituximab in refractory, seronegative, muscle-specific, kinase-positive myasthenia gravis. J Neurol Neurosurg Psychiatry 78(7):771

    PubMed  Google Scholar 

  • Bar-Or A, Calabresi PAJ, Arnold D et al (2008) Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 63:395–400

    PubMed  CAS  Google Scholar 

  • Bartok B, Silverman GJ (2011) Development of anti-CD20 therapy for multiple sclerosis. Exp Cell Res 317(9):1312–1318

    PubMed  CAS  Google Scholar 

  • Barohn RJ, Rashid I, McVey AL et al (2005) Rituximab for the treatment of IgM associated polyneuropathies. J Peripher Nerv Syst 10(Suppl 1):4

    Google Scholar 

  • Baker MR, Das M, Isaacs J et al (2005) Treatment of stiff person syndrome with rituximab. J Neurol Neurosurg Psychiatry 76(7):999–1001

    PubMed  CAS  Google Scholar 

  • Battaglia T, De Grandis E, Mirabelli-Badenier M et al (2012) Response to rituximab in 3 children with opsoclonus-myoclonus syndrome resistant to conventional treatments. Eur J Paediatr Neurol 16(2):192–195

    PubMed  Google Scholar 

  • Bedi GS, Brown AD, Delgado SR et al (2011) Impact of rituximab on relapse rate and disability in neuromyelitis optica. Mult Scler 17(10):1225–1230

    PubMed  CAS  Google Scholar 

  • Benedetti L, Franciotta D, Vigo T et al (2007a) Relapses after treatment with rituximab in a patient with multiple sclerosis and anti-myelin-associated glycoprotein polyneuropathy. Arch Neurol 64(10):1531–1533

    PubMed  Google Scholar 

  • Benedetti L, Briani C, Grandis M et al (2007b) Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M. J Peripher Nerv Syst 12:102–107

    PubMed  CAS  Google Scholar 

  • Benedetti L, Briani C, Franciotta D et al (2008) Long-term effect of rituximab in anti-MAG polineuropathy. Neurology 71:1742

    PubMed  CAS  Google Scholar 

  • Benedetti L, Briani C, Franciotta D et al (2011) Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature. J Neurol Neurosurg Psychiatry 82:306e–308e

    Google Scholar 

  • Bennett JL, Lam C, Kalluri SR et al (2009) Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol 66(5):617–629

    PubMed  CAS  Google Scholar 

  • Blum S, Gillis D, Brown H et al (2011) Use and monitoring of low dose rituximab in myasthenia gravis. J Neurol Neurosurg Psychiatry 82:659e–663e

    Google Scholar 

  • Boster A, Ankeny DP, Racke MK (2010) The potential role of B cell-targeted therapies in multiple sclerosis. Drugs 70(18):2343–2356

    PubMed  CAS  Google Scholar 

  • Bradl M, Misu T, Takahashi T et al (2009) Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol 66(5):630–643

    PubMed  CAS  Google Scholar 

  • Cocito D, Grimaldi S, Paolasso I et al (2011) Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy. A nationwide retrospective analysis. Eur J Neurol 18:1417–1421

    PubMed  CAS  Google Scholar 

  • Chaudhry V, Cornblath DR (2010) An open-label trial of rituximab in multifocal motor neuropathy. J Peripher Nerv Syst 15:196–201

    PubMed  CAS  Google Scholar 

  • Chugh PK, Kalra BS (2013) Belimumab: targeted therapy for lupus. Int J Rheum Dis 16(1):4–13

    PubMed  CAS  Google Scholar 

  • Collongues N, Casez O, Lacour A et al (2012) Rituximab in refractory and non-refractory myasthenia: a retrospective multicenter study. Muscle Nerve 46:687–691

    PubMed  CAS  Google Scholar 

  • Cree BA, Lamb S, Morgan K et al (2005) An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64:1270–1272

    PubMed  CAS  Google Scholar 

  • Cross AH, Waubant E (2011) MS and the B cell controversy. Biochim Biophys Acta 1812:231–238

    PubMed  CAS  Google Scholar 

  • Cross AH, Stark JL, Lauber J et al (2006) Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 180(1–2):63–70

    PubMed  CAS  Google Scholar 

  • Dalakas MC (2006) B cells in the pathophysiology of autoimmune neurological disorders: a credible therapeutic target. Pharmacol Ther 112:57–70

    PubMed  CAS  Google Scholar 

  • Dalakas MC (2008) B cells as therapeutic targets in autoimmune neurological disorders. Nat Clin Pract Neurol 4(10):557–567

    PubMed  CAS  Google Scholar 

  • Dalakas MC (2009) Stiff person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol 11(2):102–110

    PubMed  Google Scholar 

  • Dalakas MC, Rakocevic G, Salajegheh M et al (2009) Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol 65:286–293

    PubMed  CAS  Google Scholar 

  • Dall’Era M, Chakravarty E, Wallace D et al (2007) Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebocontrolled, dose-escalating trial. Arthritis Rheum 56(12):4142–4150

    PubMed  Google Scholar 

  • Dalmau J, Rosenfeld MR (2008) Paraneoplastic syndromes of the CNS. Lancet Neurol 7(4):327–340

    PubMed  Google Scholar 

  • Dalmau J, Lancaster E, Martinez-Hernandez E et al (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10(1):63–74

    PubMed  CAS  Google Scholar 

  • Diaz-Manera J, Martinez-Hernandez, Querol L et al (2012a) Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 78:189–193

    PubMed  CAS  Google Scholar 

  • Diaz-Manera J, Rojas-Garcia R, Illa I (2012b) Treatment strategies for myasthenia gravis: an update. Expert Opin Pharmacother 13:1873–1883

    PubMed  CAS  Google Scholar 

  • Dillon SR, Gross JA, Ansell SM et al (2006) An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov 5:235–246

    PubMed  CAS  Google Scholar 

  • Dupond JL, Essalmi L, Gil H et al (2010) Rituximab treatment of stiff-person syndrome in a patient with thymoma, diabetes mellitus and autoimmune thyroiditis. J Clin Neurosci 17(3):389–391

    PubMed  CAS  Google Scholar 

  • Fekete R, Jankovic J (2012) Childhood Stiff-Person syndrome improved with rituximab. Case Rep Neurol 4(2):92–96

    PubMed  CAS  Google Scholar 

  • Finsterer J (2005) Treatment of immune-mediated, dysimmune neuropathies. Acta Neurol Scand 112:115–125

    PubMed  CAS  Google Scholar 

  • Fitzpatrick AM, Mann CA, Barry S et al (2011) An open label clinical trial of complement inhibition in multifocal motor neuropathy. J Peripher Nerv Syst 16:84–91

    PubMed  Google Scholar 

  • Franciotta D, Salvetti M, Lolli F et al (2008) B cells and multiple sclerosis. Lancet Neurol 7:852–858

    PubMed  CAS  Google Scholar 

  • Fraussen J, Vrolix K, Martinez-Martinez P et al (2009) B cell characterization and reactivity analysis in multiple sclerosis. Autoimmun Rev 8(8):654–658

    PubMed  CAS  Google Scholar 

  • Gajra A, Vajpayee N, Grethlein SJ (2004) Response of myasthenia gravis to rituximab in a patient with non-Hodgkin lymphoma. Am J Hematol 77(2):196–197

    PubMed  Google Scholar 

  • Gensicke H, Leppert D, Yaldizli Ö et al (2012) Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis. CNS Drugs 26(1):11–37

    PubMed  CAS  Google Scholar 

  • Gorson KC, Natarajan N, Ropper AH et al (2007) Rituximab treatment in patients with Ivig-dependent immune polyneuropathy: a prospective pilot trial. Muscle Nerve 35:66–69

    PubMed  CAS  Google Scholar 

  • Graus F, Delattre JY, Antoine JC et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75(8):1135–1140

    PubMed  CAS  Google Scholar 

  • Graus F, Saiz A, Dalmau J (2010) Antibodies and neuronal autoimmune disorders of the CNS. J Neurol 257(4):509–517

    PubMed  CAS  Google Scholar 

  • Gross JA, Dillon SR, Mudri S et al (2001) TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. Impaired B cell maturation in mice lacking BLyS. Immunity 15:289–302

    PubMed  CAS  Google Scholar 

  • Gruson B, Ghomari K, Beaumont M et al (2011) Long-term response to rituximab and fludarabine combination in IgM anti-myelin-associated glycoprotein neuropathy. J Peripher Nerv Syst 16(3):180–185

    PubMed  CAS  Google Scholar 

  • Guptill JT, Sanders DB (2010) Update on muscle-specific tyrosine kinase antibody positive myasthenia gravis. Curr Opin Neurol 23(5):530–535

    PubMed  CAS  Google Scholar 

  • Hain B, Jordan K, Deschauer M et al (2006) Successful treatment of MuSK antibody-positive myasthenia gravis with rituximab. Muscle Nerve 33(4):575–580

    PubMed  Google Scholar 

  • Hartung HP (2009) Atacicept: a new B lymphocyte-targeted therapy for multiple sclerosis. Nervenarzt 80(12):1462–1472

    PubMed  Google Scholar 

  • Hauser SL, Waubant E, Arnold DL et al, for the HERMES Trial Group (2008) B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med 358:676–688

    Google Scholar 

  • Hawker K, O’Connor P, Freedman MS, for the OLYMPUS trial group (2009) Rituximab in patients with primary progressive multiple sclerosis results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 66:460–471

    Google Scholar 

  • Honnorat J, Saiz A, Giometto B et al (2001) Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 58(2):225–230

    PubMed  CAS  Google Scholar 

  • Illa I (2005) IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory myopathies: current status. J Neurol 252(Suppl 1):I14–I18

    PubMed  Google Scholar 

  • Illa I, Diaz-Manera J, Rojas-Garcia R et al (2008) Sustained response to Rituximab in anti-AChR and anti-MuSK positive Myasthenia Gravis patients. J Neuroimmunol 201–202:90–94. doi:10.1016/j.jneuroim.2008.04.039, Epub 2008 Jul 23

    PubMed  Google Scholar 

  • Ip VHL, Lau AYL, Au LWC et al (2012) Rituximab reduces attacks in Chinese patients with NMO spectrum disorders. J Neurol Sci 324(1–2):38–39, http://dx.doi.org/10.1016/j.jns.2012.09.024

    PubMed  Google Scholar 

  • Ishida K, Mitoma H, Song SY et al (1999) Selective suppression of cerebellar GABAergic transmission by an autoantibody to glutamic acid decarboxylase. Ann Neurol 46(2):263–267

    PubMed  CAS  Google Scholar 

  • Jacob A, Weinshenker BG, Violich I et al (2008) Treatment of neuromyelitis optica with rituximab. Retrospective analysis of 25 patients. Arch Neurol 65(11):1443–1448

    PubMed  Google Scholar 

  • Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 15(3):185–95

    Google Scholar 

  • Kappos L, Li D, Calabresi PA et al (2011) Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet 378:1779–1787

    PubMed  CAS  Google Scholar 

  • Katoh N, Matsuda M, Ishii W et al (2010) Successful treatment with rituximab in a patient with Stiff-Person syndrome complicated by dysthyroid ophthalmopathy. Intern Med 49(3):237–241

    PubMed  CAS  Google Scholar 

  • Kieseier BC, Lehmann HC, zu Hörste GM (2012) Autoimmune diseases of the peripheral nervous system. Autoimmun Rev 11:191–195

    PubMed  CAS  Google Scholar 

  • Kim S, Kim W, Li XF et al (2011) Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol 68(11):1412–1420

    PubMed  Google Scholar 

  • Kinoshita M, Nakatsuji Y, Kimura T et al (2009) Neuromyelitis optica: passive transfer to rats by human immunoglobulin. Biochem Biophys Res Commun 386(4):623–627

    PubMed  CAS  Google Scholar 

  • Kitsos DK, Tsiodras S, Stamboulis E et al (2012) Rituximab and multiple sclerosis. Clin Neuropharmacol 35(2):90–96

    PubMed  CAS  Google Scholar 

  • Köller H, Kieseier BC, Jander S et al (2005) Chronic inflammatory demyelinating polyneuropathy. N Engl J Med 352(13):1343–1356

    PubMed  Google Scholar 

  • Korff CM, Parvex P, Cimasoni L et al (2011) Encephalitis associated with glutamic acid decarboxylase autoantibodies in a child: a treatable condition? Arch Neurol 68(8):1065–1068

    PubMed  Google Scholar 

  • Lancaster E, Martinez-Hernandez E, Dalmau J (2011) Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 77(2):179–189

    PubMed  CAS  Google Scholar 

  • Lassman H, Brück W, Lucchinetti CF (2007) The immunopathology of multiple sclerosis: an overview. Brain Pathol 17:210–218

    Google Scholar 

  • Lebrun C, Bourg V, Tieulie N et al (2009) Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol 16(2):246–250. doi:10.1111/j.1468-1331.2008.02399.x

    PubMed  CAS  Google Scholar 

  • Lennon VA, Wingerchuk DM, Kryzer TJ et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112

    PubMed  CAS  Google Scholar 

  • Lennon VA, Kryzer TJ, Pittock SJ et al (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202(4):473–477

    PubMed  CAS  Google Scholar 

  • Levine TD, Pestronk A (1999) IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using rituximab. Neurology 52(8):1701–1704

    PubMed  CAS  Google Scholar 

  • Lindsey JW, Meulmester KM, Brod SA et al (2012) Variable results after rituximab in neuromyelitis optica. J Neurol Sci 317:103–105

    PubMed  CAS  Google Scholar 

  • Llufriu S, Castillo J, Blanco Y et al (2009) Plasma exchange for acute attacks of CNS demyelination: predictors of improvement at 6 months. Neurology 73(12):949–953

    PubMed  CAS  Google Scholar 

  • Lucchinetti CF, Mandler RN, McGavern D et al (2002) A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 125(Pt 7):1450–1461

    PubMed  Google Scholar 

  • Lulu S, Waubant E (2013) Humoral targeted immunotherapies in multiple sclerosis. Neurotherapeutics 10(1):34–43

    PubMed  CAS  Google Scholar 

  • Lunn MP, Nobile-Orazio E (2012) Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database Syst Rev 5:CD002827

    Google Scholar 

  • Maddison P, McConville J, Farrugia ME et al (2011) The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 82:671e–673e

    Google Scholar 

  • Magliozzi R, Howell O, Vora A et al (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130(Pt 4):1089–1104

    PubMed  Google Scholar 

  • Malter MP, Helmstaedter C, Urbach H et al (2010) Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 67(4):470–478

    PubMed  Google Scholar 

  • Manto MU, Laute MA, Aguera M et al (2007) Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol 61(6):544–551

    PubMed  CAS  Google Scholar 

  • McConville J, Farrugia ME, Beeson D et al (2004) Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 55(4):580–584

    PubMed  CAS  Google Scholar 

  • Mirabelli-Badenier M, Morana G, Pinto F et al (2012) Anti-glutamic acid decarboxylase limbic encephalitis without epilepsy evolving into dementia with cerebellar ataxia. Arch Neurol 69(8):1064–1066

    PubMed  Google Scholar 

  • Moscato EH, Jain A, Peng X et al (2010) Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies. Eur J Neurosci 32(2):298–309

    PubMed  Google Scholar 

  • Naismith RT, Piccio L, Lyons JA et al (2010) Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology 74(23):1860–1867

    PubMed  CAS  Google Scholar 

  • Nobile-Orazio E (2010) Update on neuropathies associated with monoclonal gammopathy of undetermined significance (2008-2010). J Peripher Nerv Syst 15(4):302–306

    PubMed  Google Scholar 

  • Nobile-Orazio E, Meucci N, Baldini L et al (2000) Long term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain 123:710–717

    PubMed  Google Scholar 

  • Nowak RJ, DiCapua DB, Zebardast N et al (2011) Response of patients with refractory myasthenia gravis to rituximab: a retrospective study. Ther Adv Neurol Disord 4(5):259–266

    PubMed  CAS  Google Scholar 

  • Pellkofer HL, Voltz R, Kuempfel T (2009) Favorable response to rituximab in a patient with anti-VGCC-positive Lambert-Eaton myasthenic syndrome and cerebellar dysfunction. Muscle Nerve 40(2):305–308

    PubMed  CAS  Google Scholar 

  • Pellkofer HL, Krumbholz M, Berthele A et al (2011) Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology 76:1310–1315

    PubMed  CAS  Google Scholar 

  • Peltola J, Kulmala P, Isojärvi J et al (2000) Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology 55(1):46–50

    PubMed  CAS  Google Scholar 

  • Pestronk A, Florence J, Miller T et al (2003) Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry 74:485–489

    PubMed  CAS  Google Scholar 

  • Petereit HF, Moeller-Hartmann W, Reske D et al (2008) Rituximab in a patient with multiple sclerosis – effect on B cells, plasma cells and intrathecal IgG synthesis. Acta Neurol Scand 117:399–403

    PubMed  CAS  Google Scholar 

  • Pittock SJ, Yoshikawa H, Ahlskog JE et al (2006) Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc 81(9):1207–1214

    PubMed  CAS  Google Scholar 

  • Plitz T (2008) Design of a four-arm, randomized, placebocontrolled phase II study of 36 weeks of atacicept monotherapy in relapsing multiple sclerosis [abstract]. Mult Scler 14(Suppl 1):173

    Google Scholar 

  • Pranzatelli MR, Tate ED, Swan JA et al (2010) B cell depletion therapy for new-onset opsoclonus-myoclonus. Mov Disord 25(2):238–242

    PubMed  Google Scholar 

  • Pranzatelli MR, Tate ED, Shenoy S et al (2012) Ofatumumab for a rituximab-allergic child with chronic-relapsing paraneoplastic opsoclonus-myoclonus. Pediatr Blood Cancer 58(6):988–991

    PubMed  Google Scholar 

  • Qureshi A, Hennessy M (2012) Stiff person syndrome (SPS) complicated by respiratory failure: successful treatment with rituximab. J Neurol 259(1):180–181

    PubMed  CAS  Google Scholar 

  • Racke MK (2008) The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies. Curr Opin Neurol 21(Suppl 1):S9–S18

    PubMed  CAS  Google Scholar 

  • Rakocevic G, Raju R, Semino-Mora C et al (2006) Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology 67(6):1068–1070

    PubMed  Google Scholar 

  • Renaud S, Gregor M, Fuhr P et al (2003) Rituximab in the treatment ofpolyneuropathy associated with anti-MAG antibodies. Muscle Nerve 27:611–615

    PubMed  CAS  Google Scholar 

  • Renaud S, Fuhr P, Gregor M et al (2006) High-dose rituximab and anti-MAG-associated polyneuropathy. Neurology 66:742

    PubMed  CAS  Google Scholar 

  • Rojas-García R, Gallardo E, de Andrés I et al (2003) Chronic neuropathy with IgM antiganglioside antibodies: lack of long term response to rituximab. Neurology 61:1814

    PubMed  Google Scholar 

  • Rommer PS, Patejdl R, Winkelmann A et al (2011) Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs 25(7):607–613

    PubMed  CAS  Google Scholar 

  • Rüegg SJ, Fuhr P, Steck AJ (2004) Rituximab stabilizes multifocal motor neuropathy increasingly less responsive to IVIg. Neurology 63:2178–2179

    PubMed  Google Scholar 

  • Saadoun S, Waters P, Bell BA et al (2010) Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 133(Pt 2):349–361

    PubMed  Google Scholar 

  • Saiz A, Blanco Y, Sabater L et al (2008) Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 131(Pt 10):2553–2563

    PubMed  Google Scholar 

  • Sánchez-Carteyron A, Alarcia R, Ara JR et al (2010) Posterior reversible encephalopathy syndrome after rituximab infusion in neuromyelitis optica. Neurology 74(18):1471–1473

    PubMed  Google Scholar 

  • Shams’ili S, de Beukelaar J, Gratama JW et al (2006) An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes. J Neurol 253:16–20

    PubMed  Google Scholar 

  • Serafini B, Rosicarelli B, Magliozzi R et al (2004) Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 14(2):164–174

    PubMed  Google Scholar 

  • Sergott R (2008) Design of an exploratory two-arm, randomized, placebo controlled phase II study of 36 weeks of atacicept treatment in patients with optic neuritis as clinically isolated syndrome [abstract]. Mult Scler 14(Suppl 1):177

    Google Scholar 

  • Sevy A, Franques J, Chiche L et al (2012) Successful treatment with rituximab in a refractory Stiff-person syndrome. Rev Neurol (Paris) 168(4):375–378

    CAS  Google Scholar 

  • Smith AG, Wald J (1996) Acute ventilatory failure in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine. Neurology 46(4):1143–1145

    PubMed  CAS  Google Scholar 

  • Sorensen P, Drulovic J, Havrdrova E et al (2010) Magnetic resonance imaging (MRI) efficacy of ofatumumab in relapsing-remitting multiple sclerosis (RRMS) – 24-week results of a phase II study. Mult Scler 16:S37

    Google Scholar 

  • Stein B, Bird SJ (2011) Rituximab in the treatment of MuSK antibody-positive myasthenia gravis. J Clin Neuromuscul Dis 12(3):163–164

    PubMed  Google Scholar 

  • Stieglbauer K, Topakian R, Hinterberger G et al (2009) Beneficial effect of rituximab monotherapy in multifocal motor neuropathy. Neuromuscul Disord 19:473–475

    PubMed  Google Scholar 

  • Tak PP, Thurlings RM, Rossier C et al (2008) Atacicept in patients with rheumatoid arthritis: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating, single and repeated-dose study. Arthritis Rheum 58(1):61–72

    PubMed  CAS  Google Scholar 

  • Thakre M, Inshasi J, Marashi M (2007) Rituximab in refractory MuSK antibody myasthenia gravis. J Neurol 254(7):968–969

    PubMed  Google Scholar 

  • Titulaer MJ, McCracken L, Gabilondo I et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12(2):157–165

    PubMed  CAS  Google Scholar 

  • Venhoff N, Rizzi M, Salzer U et al (2009) Monozygotic twins with stiff person syndrome and autoimmune thyroiditis: rituximab inefficacy in a double-blind, randomised, placebo controlled crossover study. Ann Rheum Dis 68(9):1506–1508

    PubMed  CAS  Google Scholar 

  • Vincent A, Leite MI (2005) Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol 18:519–525

    PubMed  CAS  Google Scholar 

  • Vincent A, Beeson D, Lang B (2000) Molecular targets for autoimmune and genetic disorders of neuromuscular transmission. Eur J Biochem 267(23):6717–6728

    PubMed  CAS  Google Scholar 

  • Vlam L, Van den Berg LH, Cats EA et al (2013) Immune pathogenesis and treatment of multifocal motor neuropathy. J Clin Immunol 33(Suppl 1):S38–S42

    PubMed  Google Scholar 

  • Weinshenker BG, O’Brien PC, Petterson TM et al (1999) A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 46(6):878–886

    PubMed  CAS  Google Scholar 

  • Wingerchuk DM, Hogancamp WF, O’Brien PC et al (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53(5):1107–1114

    PubMed  CAS  Google Scholar 

  • Wingerchuk DM, Lennon VA, Pittock SJ et al (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66:1485–1489

    PubMed  CAS  Google Scholar 

  • Wingerchuk DM, Lennon VA, Lucchinetti CF et al (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6(9):805–815

    PubMed  CAS  Google Scholar 

  • Yamamura T, Miyake S (2012) B-cell-directed therapy: which B cells should be targeted and how? Immunotherapy 4(5):455–457

    PubMed  CAS  Google Scholar 

  • Yeo KK, Walter AW, Miller RE et al (2012) Rituximab as potential therapy for paraneoplastic cerebellar degeneration in pediatric Hodgkin disease. Pediatr Blood Cancer 58:986–987

    PubMed  Google Scholar 

  • Zaja F, Russo D, Fuga G et al (2000) Rituximab for myasthenia gravis developing after bone marrow transplant. Neurology 55(7):1062–1063

    PubMed  CAS  Google Scholar 

  • Zara G, Zambello R, Ermani M (2011) Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy. Clin Neurophysiol 122:2518–2522

    PubMed  CAS  Google Scholar 

  • Zebardast N, Patwa HS, Novella SP et al (2010) Rituximab in the management of refractory myasthenia gravis. Muscle Nerve 41(3):375–378

    PubMed  CAS  Google Scholar 

  • Zuliani L, Graus F, Giometto B et al (2012) Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry 83(6):638–645

    PubMed  Google Scholar 

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Sepúlveda, M., Saiz, A., Graus, F. (2014). Targeting B Cells in Neurological Autoimmune Diseases. In: Bosch, X., Ramos-Casals, M., Khamashta, M. (eds) Drugs Targeting B-Cells in Autoimmune Diseases. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0348-0706-7_12

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