B cells in MS and NMO: Pathogenesis and therapy

Seminars in Immunopathology

Volumn 36, Issue 3, 2014, Pages 339-350

  Krumbholz, Markus ^a   Meinl, Edgar ^a  

^a UNIVERSITY OF MUNICH   (Germany)

Author keywords

Antibodies; B cells; Multiple sclerosis; Neuromyelitis optica; Pathogenesis; Therapy

Indexed keywords

ALEMTUZUMAB; APRIL PROTEIN; AQUAPORIN 4; ATACICEPT; AUTOANTIBODY; B CELL ACTIVATING FACTOR; B CELL ACTIVATING FACTOR RECEPTOR; BELIMUMAB; BETA1A INTERFERON; BORTEZOMIB; CD20 ANTIGEN; ECULIZUMAB; IMMUNOGLOBULIN; IMMUNOGLOBULIN G; INTERLEUKIN 10; INTERLEUKIN 35; INTERLEUKIN 6; MONOCLONAL ANTIBODY; OCRELIZUMAB; OFATUMUMAB; RITUXIMAB; TABALUMAB; TOCILIZUMAB;

ANTIBODY PRODUCTION; ANTIGEN PRESENTATION; B LYMPHOCYTE; BLOOD BRAIN BARRIER; CELL MIGRATION; CELLULAR DISTRIBUTION; CELLULAR IMMUNITY; CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL (TOPIC); CYTOKINE PRODUCTION; DRUG MECHANISM; DRUG TARGETING; HUMAN; HUMORAL IMMUNITY; IMMUNOADSORPTION; IMMUNOLOGICAL TOLERANCE; LUPUS ERYTHEMATOSUS NEPHRITIS; LYMPHOCYTE FUNCTION; MULTIPLE SCLEROSIS; MYELOOPTIC NEUROPATHY; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PATHOGENESIS; PEDIATRICS; PLASMAPHERESIS; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN TRANSPORT; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; UNSPECIFIED SIDE EFFECT; ANIMAL; CELL MOTION; DISEASE MODEL; GENE REARRANGEMENT; GENETICS; IMMUNOLOGY; NEUROMYELITIS OPTICA; TUMOR MICROENVIRONMENT;

ANIMALS; AUTOANTIBODIES; B-LYMPHOCYTES; CELL MOVEMENT; CELLULAR MICROENVIRONMENT; DISEASE MODELS, ANIMAL; GENE REARRANGEMENT, B-LYMPHOCYTE; HUMANS; IMMUNOGLOBULINS; MULTIPLE SCLEROSIS; NEUROMYELITIS OPTICA;

EID: 84902367710     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-014-0424-x     Document Type: Review

References (120)

1. Hauser S, Waubant E, Arnold D, Vollmer T, Antel J, et al. (2007). A phase II randomized, placebo-controlled, multicenter trial of rituximab in adults with relapsing remitting multiple sclerosis (RRMS) Neurology 68 (12): Suppl. 1: A99-A100
2. Pellkofer HL, Krumbholz M, Berthele A, Hemmer B, Gerdes LA et al (2011) Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology 76:1310-1315
3. Koziolek M, Tampe D, Bahr M, Dihazi H, Jung K et al (2012) Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis. J Neuroinflammation 9:80-89
4. Keegan M, Konig F, McClelland R, Bruck W, Morales Y et al (2005) Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 366:579-582 (Pubitemid 41140333)
5. Heigl F, Hettich R, Arendt R, Durner J, Koehler J et al (2013) Immunoadsorption in steroid-refractory multiple sclerosis: clinical experience in 60 patients. Atheroscler Suppl 14:167-173
6. Trebst C, Jarius S, Berthele A, Paul F, Schippling S et al (2013) Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. doi:10.1007/s00415-013-7169- 7
7. Elliott C, Lindner M, Arthur A, Brennan K, Jarius S et al (2012) Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis. Brain 135:1819-1833
8. Lisak RP, Benjamins JA, Nedelkoska L, Barger JL, Ragheb S et al (2012) Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro. J Neuroimmunol 246:85-95
9. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgGmarker of optic-spinalmultiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473-477 (Pubitemid 41186945)
10. Bradl M, Misu T, Takahashi T, Watanabe M, Mader S et al (2009) Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol 66:630-643
11. Bennett JL, Lam C, Kalluri SR, Saikali P, Bautista K et al (2009) Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol 66:617-629
12. Asgari N, Khorooshi R, Lillevang ST, Owens T (2013) Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid. J Neuroimmunol 254:76-82
13. Kitic M, Hochmeister S, Wimmer I, Bauer J, Misu T et al (2013) Intrastriatal injection of interleukin-1 beta triggers the formation of neuromyelitis optica-like lesions in NMO-IgG seropositive rats. Acta Neuropathol Commun 1:5
14. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M et al (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707-717 (Pubitemid 30390191)
15. Breij ECW, Brink BP, Veerhuis R, van den Berg C, Vloet R et al (2008) Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann Neurol 63:16-25 (Pubitemid 351240547)
16. Barnett MH, Parratt JD, Cho ES, Prineas JW (2009) Immunoglobulins and complement in postmortem multiple sclerosis tissue. Ann Neurol 65:32-46
17. Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G et al (2002) A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 125:1450-1461 (Pubitemid 34755161)
18. Misu T, Hoftberger R, Fujihara K, Wimmer I, Takai Yet al (2013) Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica. Acta Neuropathol 125:815-827
19. Lanzavecchia A (1985) Antigen-specific interaction between T and B cells. Nature 314:537-539
20. Batista FD, Harwood NE (2009) The who, how and where of antigen presentation to B cells. Nat Rev Immunol 9:15-27
21. Molnarfi N, Schulze-Topphoff U, Weber MS, Patarroyo JC, Prod'homme T et al (2013) MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J Exp Med. doi:10.1084/jem.20130699
22. Cinamon G, Zachariah MA, Lam OM, Foss FW Jr, Cyster JG (2008) Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol 9:54-62 (Pubitemid 350286204)
23. de Vos AF, van Meurs M, Brok HP, Boven LA, Hintzen RQ et al (2002) Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol 169:5415-5423 (Pubitemid 35291638)
24. von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L et al (2012) B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest 122:4533-4543
25. Mayer MC, Hohlfeld R, Meinl E Viability of autoantibody-targets: how to tackle pathogenetic heterogeneity as an obstacle for treatment of multiple sclerosis. J Neurol Sci. doi:10.1016/j.jns.2012.05.018
26. Meinl E, Krumbholz M, Hohlfeld R (2006) B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol 59:880-892 (Pubitemid 43830920)
27. Barr TA, Shen P, Brown S, Lampropoulou V, Roch T et al (2012) B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6 producing B cells. J Exp Med 209:1001-1010
28. Ireland SJ, Blazek M, Harp CT, Greenberg B, Frohman EM et al (2012) Antibody-independent B cell effector functions in relapsing remitting multiple sclerosis: clues to increased inflammatory and reduced regulatory B cell capacity. Autoimmunity 45:400-414
29. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3:944-950 (Pubitemid 35154008)
30. Shen P, Roch T, Lampropoulou V, O'Connor RA, Hilgenberg E et al (2014) IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 507(7492):366-70
31. Bosma A, Abdel-Gadir A, Isenberg David A, Jury Elizabeth C, Mauri C (2012) Lipid-antigen presentation by CD1d+B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36:477-490
32. Godfrey DI, Kronenberg M (2004) Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 114:1379-1388 (Pubitemid 40385565)
33. Yoshizaki A, Miyagaki T, DiLillo DJ, Matsushita T, Horikawa M et al (2012) Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 491:264-268
34. Bettelli E, Das MP, Howard ED, Weiner HL, Sobel RA et al (1998) IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol 161:3299-3306
35. Cohen SJ, Cohen IR, Nussbaum G (2010) IL-10mediates resistance to adoptive transfer experimental autoimmune encephalomyelitis in MyD88(-/-) mice. J Immunol 184:212-221
36. Kessel A, Haj T, Peri R, Snir A, Melamed D et al (2012) Human CD19+CD25high B regulatory cells suppress proliferation of CD4+ T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells. Autoimmun Rev 11:670-677
37. Mauri C, Blair PA (2010) Regulatory B cells in autoimmunity: developments and controversies. Nat Rev Rheumatol 6:636-643
38. Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P et al (2011) Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remission. J Neuroimmunol 239:80-86
39. Quan C, Yu H, Qiao J, Xiao B, Zhao G et al (2013) Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct frommultiple sclerosis.Mult Scler J 19:289-298
40. Wang HH, Dai YQ, Qiu W, Lu ZQ, Peng FH et al (2011) Interleukin-17- secreting Tcells in neuromyelitis optica andmultiple sclerosis during relapse. J Clin Neurosci 18:1313-1317
41. Wu A, Zhong X, Wang H, Xu W, Cheng C et al (2012) Cerebrospinal fluid IL-21 levels in neuromyelitis optica and multiple sclerosis. Can J Neurol Sci 39:813-820
42. Ding BB, Bi E, Chen H, Yu JJ, Ye BH (2013) IL-21 and CD40L synergistically promote plasma cell differentiation through upregulation of Blimp-1 in human B cells. J Immunol 190:1827-1836
43. Korn T, Bettelli E, Gao W, Awasthi A, Jager A et al (2007) IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 448:484-487 (Pubitemid 47123515)
44. Schwab I, Nimmerjahn F (2013) Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol 13:176-189
45. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E et al (2003) Predominant autoantibody production by early human B cell precursors. Science 301:1374-1377 (Pubitemid 37075812)
46. Meffre E, Wardemann H (2008) B-cell tolerance checkpoints in health and autoimmunity. Curr Opin Immunol 20:632-638
47. Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M et al (2013) Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest 123:2737-2741
48. Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A et al (2010) Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 67:452-461
49. Bennett JL, Haubold K, Ritchie AM, Edwards SJ, Burgoon M et al (2008) CSF IgG heavy-chain bias in patients at the time of a clinically isolated syndrome. J Neuroimmunol 199:126-132
50. Ligocki AJ, Rounds WH, Cameron EM, Harp CT, Frohman EM et al (2013) Expansion of CD27(high) plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation. Genes and Immunity 14:291-301
51. Krumbholz M, Derfuss T, Hohlfeld R, Meinl E (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613-623
52. Hayashi T, Matsumoto I, Yasukochi T, Mamura M, Goto D et al (2007) Biased usage of synovial immunoglobulin heavy chain variable region 4 by the anti-glucose-6-phosphate isomerase antibody in patients with rheumatoid arthritis. Int J Mol Med 20:247-253
53. Huang SC, Jiang R, Hufnagle WO, Furst DE, Wilske KR et al (1998) VH usage and somatic hypermutation in peripheral blood B cells of patients with rheumatoid arthritis (RA). Clin Exp Immunol 112:516-527 (Pubitemid 28267436)
54. Dorner T, Farner NL, Lipsky PE (1999) Ig lambda and heavy chain gene usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation. J Immunol 163:1027-1036 (Pubitemid 29328116)
55. Fraser NL, Rowley G, Field M, Stott DI (2003) The VH gene repertoire of splenic B cells and somatic hypermutation in systemic lupus erythematosus. Arthritis Res Ther 5:R114-R121
56. Cameron EM, Spencer S, Lazarini J, Harp CT, Ward ES et al (2009) Potential of a unique antibody gene signature to predict conversion to clinically definite multiple sclerosis. J Neuroimmunol 213:123-130
57. Ligocki AJ, Lovato L, Xiang D, Guidry P, Scheuermann RH et al (2010) A unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis. J Neuroimmunol 226:192-193
58. Derfuss T, Meinl E (2012) Identifying autoantigens in demyelinating diseases: valuable clues to diagnosis and treatment? Curr Opin Neurol 25:231-238
59. Brickshawana A, Hinson SR, Fryer JP, McKeon A, Pittock SJ, et al. (2013). KIR4.1-Specific IgG Not Detected in Multiple Sclerosis Patients ' Sera (S506). Presented at Annual Meeting of the American Neurological Association, New Orleans, Louisiana, USA
60. Querol L, Clark PL, Bailey MA, Cotsapas C, Cross AH et al (2013) Protein array-based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis. Neurology. doi:10.1212/WNL.0b013e3182a43b48
61. Reindl M, Di Pauli F, Rostasy K, Berger T (2013) The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 9:455-461
62. O'Connor KC, McLaughlin KA, De Jager PL, Chitnis T, Bettelli E et al (2007) Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med 13:211-217
63. Rostasy K, Mader S, Schanda K, Huppke P, Gartner J, et al. (2012). Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol
64. Pröbstel AK, Dornmair K, Bittner R, Sperl P, Jenne D et al (2011) Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 77:580-588
65. Mayer MC, Breithaupt C, Reindl M, Schanda K, Rostasy K et al (2013) Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases. J Immunol 191:3594-3604
66. Hacohen Y, Absoud M, Woodhall M, Cummins C, De Goede CG et al (2013) Autoantibody biomarkers in childhood-acquired demyelinating syndromes: results from a national surveillance cohort. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2013-306411
67. Titulaer MJ, Hoftberger R, Iizuka T, Rosenfeld MR, Graus F, et al. (2013). Overlap of Anti-NMDAR Encephalitis with Demyelinating Disorders (S528WIP). Presented at Annual Meeting of the American Neurological Association, New Orleans, Louisiana, USA
68. Ratelade J, Zhang H, Saadoun S, Bennett JL, Papadopoulos MC et al (2012) Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss. Acta Neuropathol (Berl) 123:861-872
69. Kitley J, Woodhall M, Waters P, Leite MI, Devenney E et al (2012) Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 79:1273-1277
70. Mader S, Gredler V, Schanda K, Rostasy K, Dujmovic I, et al. (2011). Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation. 8:184.: 184
71. Waters P, Woodhall M, Hacohen Y, O'Connor K, Absoud M, et al. (2013). Antibodies to myelin oligodendrocyte glycoprotein (MOG) in children and adults with demyelinating disorders (NMO) (S503). Presented at Annual Meeting of the American Neurological Association, New Orleans, Louisiana, USA
72. Woodhall M, Coban A, Waters P, Ekizoglu E, Kurtuncu M et al (2013) Glycine receptor and myelin oligodendrocyte glycoprotein antibodies in Turkish patients with neuromyelitis optica. J Neurol Sci 335:221-223
73. Tzartos JS, Stergiou C, Kilidireas K, Zisimopoulou P, Thomaidis T et al (2013) Anti-Aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders. PLoS One 8:e74773
74. Harrer A, Tumani H, Niendorf S, Lauda F, Geis C et al (2013) Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy. Mult Scler J 19: 1209-1212
75. Krumbholz M, Meinl I, Kümpfel T, Hohlfeld R, Meinl E (2008) Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis. Neurology 71:1350-1354
76. Stangel M, Fredrikson S, Meinl E, Petzold A, Stuve O et al (2013) The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat Rev Neurol 9:267-276
77. Krumbholz M, Theil D, Derfuss T, Rosenwald A, Schrader F et al (2005) BAFF is produced by astrocytes and up-regulated inmultiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 201:195-200 (Pubitemid 40189428)
78. Kowarik M, Cepok S, Sellner J, Grummel V, Weber M et al (2012) CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation 9:93
79. Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P et al (2006) Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129:200-211 (Pubitemid 43063771)
80. Brettschneider J, Czerwoniak A, Senel M, Fang L, Kassubek J et al (2010) The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS One 5:e11986
81. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F (2004) Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 14:164-174 (Pubitemid 38656388)
82. Tada S, Yasui T, Nakatsuji Y, Okuno T, Koda T et al (2013) BAFF controls neural cell survival through BAFF receptor. PLoS One 8:e70924
83. Zhang L, Zheng S, Wu H, Wu Y, Liu S et al (2009) Identification of BLyS (B lymphocyte stimulator), a non-myelin-associated protein, as a functional ligand for Nogo-66 receptor. J Neurosci 29:6348-6352
84. Li M, Ransohoff RM (2008) Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol 84:116-131
85. Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, Nelson PA, Stroud RM et al (2012) Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann Neurol 72:53-64
86. Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, et al. (2011). Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature advance online publication: 538-41
87. Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A et al (2011) Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet 378:1779-1787
88. Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ et al (2012) Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 380:1819-1828
89. Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C et al (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380:1829-1839
90. Hartung HP, Kieseier BC (2010) Atacicept: targeting B cells in multiple sclerosis. Ther Adv Neurol Disord 3:205-216
91. Lesley R, Xu Y, Kalled SL, Hess DM, Schwab SR et al (2004) Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity 20:441-453 (Pubitemid 38482122)
92. Yang M, Sun L, Wang S, Ko KH, Xu H et al (2010) Cutting edge: novel function of B cell-activating factor in the induction of IL-10 producing regulatory B cells. J Immunol 184:3321-3325
93. Papadopoulos MC, Verkman AS (2013) Aquaporin water channels in the nervous system. Nat Rev Neurosci 14:265-277
94. Tradtrantip L, Zhang H, Saadoun S, Phuan P-W, Lam C et al (2012) Anti-Aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol 71:314-322
95. Tradtrantip L, Zhang H, Anderson MO, Saadoun S, Phuan PW et al (2012) Small-molecule inhibitors of NMO-IgG binding to aquaporin-4 reduce astrocyte cytotoxicity in neuromyelitis optica. FASEB J 26:2197-2208
96. Yoshida M, Tamura Y, Yamada Y, Yamawaki N, Yamashita Y (1998) Immusorba TR and Immusorba PH: basics of design and features of functions. Ther Apher 2:185-192 (Pubitemid 28402321)
97. Elsone L, Panicker J, Mutch K, Boggild M, Appleton R et al (2013) Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler J. doi:10.1177/1352458513495938
98. Kuroda H, Fujihara K, Takano R, Takai Y, Takahashi T et al (2013) Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J Neuroimmunol 254:178-182
99. Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG et al (2013) Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol 12:554-562
100. Benkhoucha M, Molnarfi N, Santiago-Raber ML, Weber MS, Merkler D et al (2012) IgG glycan hydrolysis by EndoS inhibits experimental autoimmune encephalomyelitis. J Neuroinflammation 9:209
101. Maeda K, Mehta H, Drevets DA, Coggeshall KM (2010) IL-6 increases B-cell IgG production in a feed-forward proinflammatory mechanism to skew hematopoiesis and elevate myeloid production. Blood 115:4699-4706
102. Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S et al (2011) Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci USA 108:3701-3706
103. Icoz S, Tuzun E, Kurtuncu M, Durmus H, Mutlu M et al (2010) Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients. Int J Neurosci 120:71-75
104. Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, et al. (2012). Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab.Mod Rheumatol 1-5. doi:10.1007/s10165-012-0715-9
105. Kieseier BC, Stüve O, Dehmel T, Goebels N, Leussink VI, et al. (2012). Disease amelioration with tocilizumab in a treatmentresistant patient with neuromyelitis optica: implication for cellular immune responses. Arch Neurol 1-4. doi:10.1001/jamaneurol.2013.668
106. Ayzenberg I, Kleiter I, Schroder A, Hellwig K, Chan A et al (2013) Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 70:394-397
107. Mihara M, Kasutani K, Okazaki M, Nakamura A, Kawai S et al (2005) Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol 5:1731-1740 (Pubitemid 41116745)
108. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochimic et Biophys Acta (BBA) - Mol Cell Res 1813:878-888
109. Leibinger M, Muller A, Gobrecht P, Diekmann H, Andreadaki A et al (2013) Interleukin-6 contributes to CNS axon regeneration upon inflammatory stimulation. Cell Death Dis 4:e609
110. Yang P, Wen H, Ou S, Cui J, Fan D (2012) IL-6 promotes regeneration and functional recovery after cortical spinal tract injury by reactivating intrinsic growth program of neurons and enhancing synapse formation. Exp Neurol 236:19-27
111. Haggiag S, Zhang PL, Slutzky G, Shinder V, Kumar A et al (2001) Stimulation of myelin gene expression in vitro and of sciatic nerve remyelination by interleukin-6 receptor-interleukin-6 chimera. J Neurosci Res 64:564-574 (Pubitemid 32520677)
112. Valerio A, Ferrario M, Dreano M, Garotta G, Spano P et al (2002) Soluble interleukin-6 (IL-6) receptor/IL-6 fusion protein enhances in vitro differentiation of purified rat oligodendroglial lineage cells. Mol Cell Neurosci 21:602-615 (Pubitemid 36062717)
113. Zhang PL, Izrael M, Ainbinder E, Ben-Simchon L, Chebath J et al (2006) Increased myelinating capacity of embryonic stem cell derived oligodendrocyte precursors after treatment by interleukin-6/soluble interleukin-6 receptor fusion protein. Mol Cell Neurosci 31:387-398 (Pubitemid 43358014)
114. Pizzi M, Sarnico I, Boroni F, Benarese M, Dreano M et al (2004) Prevention of neuron and oligodendrocyte degeneration by interleukin-6 (IL-6) and IL-6 receptor/IL-6 fusion protein in organotypic hippocampal slices. Mol Cell Neurosci 25:301-311 (Pubitemid 38338641)
115. Tradtrantip L, Ratelade J, Zhang H, Verkman AS (2013) Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti-aquaporin-4 immunoglobulin G into therapeutic antibody. Ann Neurol 73:77-85
116. Fulciniti M, Hideshima T, Vermot-Desroches C, Pozzi S, Nanjappa P et al (2009) A high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma. Clin Cancer Res 15:7144-7152
117. Jarius S, Wildemann B (2010) AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 6:383-392
118. Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B et al (2010) Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 291:52-56
119. Jarius S, Franciotta D, Bergamaschi R, Rauer S, Wandinger KP et al (2008) Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry 79:1134-1136
120. Pedotti R, Musio S, Scabeni S, Farina C, Poliani PL et al (2013) Exacerbation of experimental autoimmune encephalomyelitis by passive transfer of IgG antibodies from a multiple sclerosis patient responsive to immunoadsorption. J Neuroimmunol 262:19-26