Role of Autoantibodies in Acquired Inflammatory Demyelinating Diseases of the Central Nervous System in Children

Abstract

The recent detection of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) autoantibodies in acquired inflammatory demyelinating diseases, such as neuromyelitis optica, or acute disseminated encephalomyelitis, and multiple sclerosis, in children strongly indicates that B-cell–dependent mechanisms contribute to the pathogenesis. This review aims to give an overview of the role of autoantibodies in inflammatory demyelinating pediatric diseases, with a focus on antibodies to AQP4 and MOG.

Keywords

children - anti-MOG antibodies - MS - ADEM

• References

• 1 Krupp LB, Tardieu M, Amato MP , et al; the International Pediatric Multiple Sclerosis Study Group. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 2013; 19 (10) 1261-1267
• 2 Krumbholz M, Derfuss T, Hohlfeld R, Meinl E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 2012; 8 (11) 613-623
• 3 Pohl D, Rostasy K, Reiber H, Hanefeld F. CSF characteristics in early-onset multiple sclerosis. Neurology 2004; 63 (10) 1966-1967
• 4 Lennon VA, Wingerchuk DM, Kryzer TJ , et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364 (9451) 2106-2112
• 5 Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66 (10) 1485-1489
• 6 Papadopoulos MC, Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol 2012; 11 (6) 535-544
• 7 Reindl M, Di Pauli F, Rostásy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013; 9 (8) 455-461
• 8 Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6 (9) 805-815
• 9 Waters PJ, McKeon A, Leite MI , et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology 2012; 78 (9) 665-671 , discussion 669
• 10 Marignier R, Bernard-Valnet R, Giraudon P , et al; NOMADMUS Study Group. Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity. Neurology 2013; 80 (24) 2194-2200
• 11 McKeon A, Lennon VA, Lotze T , et al. CNS aquaporin-4 autoimmunity in children. Neurology 2008; 71 (2) 93-100
• 12 Banwell B, Tenembaum S, Lennon VA , et al. Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology 2008; 70 (5) 344-352
• 13 Huppke P, Blüthner M, Bauer O , et al. Neuromyelitis optica and NMO-IgG in European pediatric patients. Neurology 2010; 75 (19) 1740-1744
• 14 Collongues N, Marignier R, Zéphir H , et al. Long-term follow-up of neuromyelitis optica with a pediatric onset. Neurology 2010; 75 (12) 1084-1088
• 15 Rostásy K, Mader S, Hennes E , et al. Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica. Mult Scler 2013; 19 (8) 1052-1059
• 16 Iglesias A, Bauer J, Litzenburger T, Schubart A, Linington C. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 2001; 36 (2) 220-234
• 17 Mayer MC, Meinl E. Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more. Ther Adv Neurol Disord 2012; 5 (3) 147-159
• 18 O'Connor KC, McLaughlin KA, De Jager PL , et al. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med 2007; 13 (2) 211-217
• 19 McLaughlin KA, Chitnis T, Newcombe J , et al. Age-dependent B cell autoimmunity to a myelin surface antigen in pediatric multiple sclerosis. J Immunol 2009; 183 (6) 4067-4076
• 20 Brilot F, Dale RC, Selter RC , et al. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol 2009; 66 (6) 833-842
• 21 Lalive PH, Häusler MG, Maurey H , et al. Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate demyelinating diseases from viral encephalitis in children. Mult Scler 2011; 17 (3) 297-302
• 22 Pröbstel AK, Dornmair K, Bittner R , et al. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 2011; 77 (6) 580-588
• 23 Di Pauli F, Mader S, Rostásy K , et al. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin Immunol 2011; 138 (3) 247-254
• 24 Mader S, Gredler V, Schanda K , et al. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation 2011; 8: 184
• 25 Kitley J, Woodhall M, Waters P , et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012; 79 (12) 1273-1277
• 26 Rostásy K, Mader S, Schanda K , et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol 2012; 69 (6) 752-756
• 27 Huppke P, Rostásy K, Karenfort M , et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler 2013; 19 (7) 941-946
• 28 O'Connor KC, Lopez-Amaya C, Gagne D , et al. Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol 2010; 223 (1-2) 92-99
• 29 Van Haren K, Tomooka BH, Kidd BA , et al. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing- remitting multiple sclerosis. Mult Scler 2013; ; doi: 10.1177/1352458513485653
• 30 Johns TG, Bernard CC. The structure and function of myelin oligodendrocyte glycoprotein. J Neurochem 1999; 72 (1) 1-9
• 31 Rostásy K, Nagl A, Lütjen S , et al. Clinical outcome of children presenting with a severe manifestation of acute disseminated encephalomyelitis. Neuropediatrics 2009; 40 (5) 211-217