The role of complement signaling pathway in the pathogenesis of neuromyelitis optica_Chinese Journal of Ocular Fundus Diseases

Authors：

Cao Shanshan ,  Wei Shihui

Department of Ophthalmology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China;

Corresponding author：

Wei Shihui, Email: weishihui706@hotmail.com

Keywords：

Neuromyelitis optica; Complement C1; Complement C3; Complement C5; Review

DOI：

10.3760/cma.j.issn.1005-1015.2019.03.019

Video：

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Abstract Full text Figures/Tables Video References Cited by

Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.

Citation： Cao Shanshan, Wei Shihui. The role of complement signaling pathway in the pathogenesis of neuromyelitis optica. Chinese Journal of Ocular Fundus Diseases, 2019, 35(3): 291-295. doi: 10.3760/cma.j.issn.1005-1015.2019.03.019 Copy

1.	Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance[J]. Nat Rev Neurol, 2010, 6(7): 383-392. DOI: 10.1038/nrneurol.2010.72.
2.	Asgari N, Lillevang ST, Skejoe HP, et al. A population-based study of neuromyelitis optica in Caucasians[J]. Neurology, 2011, 76(18): 1589-1595. DOI: 10.1212/WNL.0b013e3182190f74.
3.	Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system[J]. Nat Rev Neurosci, 2012, 14(4): 265-277. DOI: 10.1038/nrn3468.
4.	Papadopoulos MC, Verkman AS. Aquaporin 4 and neuromyelitis optica[J]. Lancet Neurol, 2013, 11(6): 535-544. DOI: 10.1016/S1474-4422(12)70133-3.
5.	Wu Y, Zhong L, Geng J. Neuromyelitis optica spectrum disorder: Pathogenesis, treatment, and experimental models[J]. Mult Scler Relat Disord, 2019, 27: 412-418. DOI: 10.1016/j.msard.2018.12.002.
6.	Wajih B, Michael HB, Kerri P, et al. Molecular pathogenesis of neuromyelitis optica[J]. Int J Mol Sci, 2012, 13(10): 12970-12993. DOI: 10.3390/ijms131012970.
7.	Kalluri SR, Illes Z, Srivastava R, et al. Quantification and functional characterization of antibodies to native aquaporin 4 in neuromyelitis optica[J]. Arch Neurol, 2010, 67(10): 1201-1208. DOI: 10.1001/archneurol.2010.269.
8.	Bradl M, Misu T, Takahashi T, et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo[J]. Ann Neurol, 2009, 66(5): 630-643. DOI: 10.1002/ana.21837.
9.	Kinoshita M, Nakatsuji Y, Kimura T, et al. Neuromyelitis optica: passive transfer to rats by human immunoglobulin[J]. Biochem Biophys Res Commun, 2009, 386(4): 623-627. DOI: 10.1016/j.bbrc.2009.06.085.
10.	Saadoun S, Waters P, Bell BA, et al. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice[J]. Brain, 2010, 133(Pt 2): 349-361. DOI: 10.1093/brain/awp309.
11.	Li L, Zhang H, Varrin-Doyer M, et al. Proinflammatory role of aquaporin-4 in autoimmune neuroinflammation[J]. FASEB J, 2011, 25(5): 1556-1566. DOI: 10.1096/fj.10-177279.
12.	Asgari N, Khorooshi R, Lillevang ST. Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid[J]. J Neuroimmunol, 2013, 254(1-2): 76-82. DOI: 10.1016/j.jneuroim.2012.09.010.
13.	Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre[J]. Brain, 2007, 130(Pt 5): 1235-1243. DOI: 10.1093/brain/awm062.
14.	Jarius S, Aboul-Enein F, Waters P, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica[J]. Brain, 2008, 131(Pt 11): 3072-3080. DOI: 10.1093/brain/awn240.
15.	Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica[J]. Brain, 2002, 125(Pt 7): 1450-1461.
16.	Roemer SF, Parisi JE, Lennon VA, et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neu-romyelitis optica from multiple sclerosis[J]. Brain, 2007, 130(Pt 5): 1194-1205. DOI: 10.1093/brain/awl371.
17.	Wingerchuk DM, Lucchinetti CF. Comparative immunopathogen-esis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis[J]. Curr Opin Neurol, 2007, 20(3): 343-350. DOI: 10.1097/WCO.0b013e3280be58d8.
18.	Misu T, Fujihara K, Kakita A, et al. Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from mul-tiple sclerosis[J]. Brain, 2007, 130(Pt 5): 1224-1234. DOI: 10.1093/brain/awm047.
19.	Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica[J]. Neurology, 2007, 69(24): 2221-2231. DOI: 10.1212/01.WNL.0000289761.64862.ce.
20.	Hinson SR, Roemer SF, Lucchinetti CF, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2[J]. J Exp Med, 2008, 205(11): 2473-2481. DOI: 10.1084/jem.20081241.
21.	Vincent T, Saikali P, Cayrol R, et al. Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment[J]. J Immunol, 2008, 181(8): 5730-5737. DOI: 10.4049/jimmunol.181.8.5730.
22.	Marignier R, Nicolle A, Watrin C, et al. Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury[J]. Brain, 2010, 133(9): 2578-2591. DOI: 10.1093/brain/awq177.
23.	Amiry-Moghaddam M, Ottersen OP. The molecular basis of water transport in the brain[J]. Nat Rev Neurosci, 2003, 4(12): 991-1001. DOI: 10.1038/nrn1252.
24.	Wolburg H, Wolburg-Buchholz K, Fallier-Becker P, et al. AF Structure and functions of aquaporin-4-based orthogonal arrays of particles[J]. Int Rev Cell Mol Biol, 2011, 287: 1-41. DOI: 10.1016/B978-0-12-386043-9.00001-3.
25.	Furman CS, Gorelick-Feldman DA, Davidson KG, et al. Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms[J]. Proc Natl Acad Sci USA, 2003, 100(23): 13609-13614. DOI: 10.1073/pnas.2235843100.
26.	Ketelslegers IA, Modderman PW, Vennegoor A, et al. Antibodies against aquaporin-4 in neuromyelitis optica: Distinction between recurrent and monophasic patients[J]. Mult. Scler, 2011, 17(12): 1527-1530. DOI: 10.1177/1352458511412995.
27.	Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis[J]. Lancet, 2004, 364(9451): 2106-2112. DOI: 10.1016/S0140-6736(04)17551-X.
28.	Crane JM, Lam C, Rossi A, et al. Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays[J]. J Biol Chem, 2011, 286(18): 16516-16524. DOI: 10.1074/jbc.M111.227298.
29.	Tani T, Sakimura K, Tsujita M, et al. Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica[J]. J Neuroimmunol, 2009, 211(1-2): 110-113. DOI: 10.1016/j.jneuroim.2009.04.001.
30.	Tradtrantip L, Jin BJ, Yao X, et al. Aquaporin-targeted therapeutics: state-of-the-field[J]. Adv Exp Med Biol, 2017, 969: 239-250. DOI: 10.1007/978-94-024-1057-0_16.
31.	Ratelade J, Bennett JL, Verkman AS. Intravenous neuromyelitis optica autoantibody in mice targets aquaporin-4 in peripheral organs and area postrema[J/OL]. PLoS One, 2011, 6 (11): 27412[2011-11-04]. https://doi.org/10.1371/journal.pone.0027412. DOI: 10.1371/journal.pone.0027412.
32.	Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica[J]. Proc Natl Acad Sci USA, 2011, 108(9): 3701-3706. DOI: 10.1073/pnas.1017385108.
33.	Zhang H, Verkman AS. Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59[J]. J Autoimmun, 2014, 53: 67-77. DOI: 10.1016/j.jaut.2014.02.011.
34.	Macedo AC, Isaac L. Systemic lupus erythematosus and deficiencies of early components of the complement classical pathway[J]. Front Immunol, 2016, 7: 55. DOI: 10.3389/fimmu.2016.00055.
35.	Tüzün E, Kürtüncü M, Türkoğlu R, et al. Enhanced complement consumption in neuromyelitis optica and Behçet’s disease patients[J]. J Neuroimmunol, 2011, 233(1-2): 211-215. DOI: 10.1016/j.jneuroim.2010.11.010.
36.	Kuroda H, Fujihara K, Takano R, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica[J]. J Neuroimmunol, 2013, 254(1-2): 178-182. DOI: 10.1016/j.jneuroim.2012.09.002.
37.	Nytrova P, Potlukova E, Kemlink D, et al. Complement activation in patients with neuromyelitis optica[J]. J Neuroimmunol, 2014, 274(1-2): 185-191. DOI: 10.1016/j.jneuroim.2014.07.001.
38.	Lubbers R,van Essen MF,van Kooten C,et al. Production of complement components by cells of the immune system[J]. Clin Exp Immunol, 2017, 188(2): 183-194. DOI: 10.1111/cei.12952.
39.	Chen Y, Li R, Wu AM, et al. The complement and immunoglobulin levels in NMO patients[J]. Neurol Sci, 2014, 35(2): 215-220. DOI: 10.1007/s10072-013-1481-y.
40.	Phuan PW, Zhang H, Asavapanumas N, et al. C1q-targeted monoclonal antibody prevents complement dependent cytotoxicity and neuropathology in in vitro and mouse models of neuromyelitis optica[J]. Acta Neuropathol, 2013, 125(6): 829-840. DOI: 10.1007/s00401-013-1128-3.
41.	Tradtrantip L, Asavapanumas N, Phuan PW, et al. Potential therapeutic benefit of C1-esterase inhibitor in neuromyelitis optica evaluated in vitro and in an experimental rat model [J/OL]. PLoS One, 2014, 9(9): 106824[2014-09-05]. https://doi.org/10.1371/journal.pone.0106824. DOI: 10.1371/journal.pone.0106824.
42.	van Beek J, Nicole O, Ali C, et al. Complement anaphylatoxin C3a is selectively protective against NMDA-induced neuronal cell death[J]. Neuroreport, 2001, 12(2): 289-293. DOI: 10.1097/00001756-200102120-00022.
43.	Uzawa A, Mori M, Sawai S, et al. Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks[J]. Clin Chim Acta, 2013, 421: 181-183. DOI: 10.1016/j.cca.2013.03.020.
44.	Woodruff TM, Nandakumar KS, Tedesco F. Inhibiting the C5-C5a receptor axis[J]. Mol Immunol, 2011, 48(14): 1631-642. DOI: 10.1016/j.molimm.2011.04.014.
45.	Pittock SJ, Lennon VA, McKeon A, et al. Eculizumab in □AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study[J]. Lancet Neurol, 2013, 12(6): 554-562. DOI: 10.1016/S1474-4422(13)70076-0.

1. Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance[J]. Nat Rev Neurol, 2010, 6(7): 383-392. DOI: 10.1038/nrneurol.2010.72.
2. Asgari N, Lillevang ST, Skejoe HP, et al. A population-based study of neuromyelitis optica in Caucasians[J]. Neurology, 2011, 76(18): 1589-1595. DOI: 10.1212/WNL.0b013e3182190f74.
3. Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system[J]. Nat Rev Neurosci, 2012, 14(4): 265-277. DOI: 10.1038/nrn3468.
4. Papadopoulos MC, Verkman AS. Aquaporin 4 and neuromyelitis optica[J]. Lancet Neurol, 2013, 11(6): 535-544. DOI: 10.1016/S1474-4422(12)70133-3.
5. Wu Y, Zhong L, Geng J. Neuromyelitis optica spectrum disorder: Pathogenesis, treatment, and experimental models[J]. Mult Scler Relat Disord, 2019, 27: 412-418. DOI: 10.1016/j.msard.2018.12.002.
6. Wajih B, Michael HB, Kerri P, et al. Molecular pathogenesis of neuromyelitis optica[J]. Int J Mol Sci, 2012, 13(10): 12970-12993. DOI: 10.3390/ijms131012970.
7. Kalluri SR, Illes Z, Srivastava R, et al. Quantification and functional characterization of antibodies to native aquaporin 4 in neuromyelitis optica[J]. Arch Neurol, 2010, 67(10): 1201-1208. DOI: 10.1001/archneurol.2010.269.
8. Bradl M, Misu T, Takahashi T, et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo[J]. Ann Neurol, 2009, 66(5): 630-643. DOI: 10.1002/ana.21837.
9. Kinoshita M, Nakatsuji Y, Kimura T, et al. Neuromyelitis optica: passive transfer to rats by human immunoglobulin[J]. Biochem Biophys Res Commun, 2009, 386(4): 623-627. DOI: 10.1016/j.bbrc.2009.06.085.
10. Saadoun S, Waters P, Bell BA, et al. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice[J]. Brain, 2010, 133(Pt 2): 349-361. DOI: 10.1093/brain/awp309.
11. Li L, Zhang H, Varrin-Doyer M, et al. Proinflammatory role of aquaporin-4 in autoimmune neuroinflammation[J]. FASEB J, 2011, 25(5): 1556-1566. DOI: 10.1096/fj.10-177279.
12. Asgari N, Khorooshi R, Lillevang ST. Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid[J]. J Neuroimmunol, 2013, 254(1-2): 76-82. DOI: 10.1016/j.jneuroim.2012.09.010.
13. Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre[J]. Brain, 2007, 130(Pt 5): 1235-1243. DOI: 10.1093/brain/awm062.
14. Jarius S, Aboul-Enein F, Waters P, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica[J]. Brain, 2008, 131(Pt 11): 3072-3080. DOI: 10.1093/brain/awn240.
15. Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica[J]. Brain, 2002, 125(Pt 7): 1450-1461.
16. Roemer SF, Parisi JE, Lennon VA, et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neu-romyelitis optica from multiple sclerosis[J]. Brain, 2007, 130(Pt 5): 1194-1205. DOI: 10.1093/brain/awl371.
17. Wingerchuk DM, Lucchinetti CF. Comparative immunopathogen-esis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis[J]. Curr Opin Neurol, 2007, 20(3): 343-350. DOI: 10.1097/WCO.0b013e3280be58d8.
18. Misu T, Fujihara K, Kakita A, et al. Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from mul-tiple sclerosis[J]. Brain, 2007, 130(Pt 5): 1224-1234. DOI: 10.1093/brain/awm047.
19. Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica[J]. Neurology, 2007, 69(24): 2221-2231. DOI: 10.1212/01.WNL.0000289761.64862.ce.
20. Hinson SR, Roemer SF, Lucchinetti CF, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2[J]. J Exp Med, 2008, 205(11): 2473-2481. DOI: 10.1084/jem.20081241.
21. Vincent T, Saikali P, Cayrol R, et al. Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment[J]. J Immunol, 2008, 181(8): 5730-5737. DOI: 10.4049/jimmunol.181.8.5730.
22. Marignier R, Nicolle A, Watrin C, et al. Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury[J]. Brain, 2010, 133(9): 2578-2591. DOI: 10.1093/brain/awq177.
23. Amiry-Moghaddam M, Ottersen OP. The molecular basis of water transport in the brain[J]. Nat Rev Neurosci, 2003, 4(12): 991-1001. DOI: 10.1038/nrn1252.
24. Wolburg H, Wolburg-Buchholz K, Fallier-Becker P, et al. AF Structure and functions of aquaporin-4-based orthogonal arrays of particles[J]. Int Rev Cell Mol Biol, 2011, 287: 1-41. DOI: 10.1016/B978-0-12-386043-9.00001-3.
25. Furman CS, Gorelick-Feldman DA, Davidson KG, et al. Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms[J]. Proc Natl Acad Sci USA, 2003, 100(23): 13609-13614. DOI: 10.1073/pnas.2235843100.
26. Ketelslegers IA, Modderman PW, Vennegoor A, et al. Antibodies against aquaporin-4 in neuromyelitis optica: Distinction between recurrent and monophasic patients[J]. Mult. Scler, 2011, 17(12): 1527-1530. DOI: 10.1177/1352458511412995.
27. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis[J]. Lancet, 2004, 364(9451): 2106-2112. DOI: 10.1016/S0140-6736(04)17551-X.
28. Crane JM, Lam C, Rossi A, et al. Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays[J]. J Biol Chem, 2011, 286(18): 16516-16524. DOI: 10.1074/jbc.M111.227298.
29. Tani T, Sakimura K, Tsujita M, et al. Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica[J]. J Neuroimmunol, 2009, 211(1-2): 110-113. DOI: 10.1016/j.jneuroim.2009.04.001.
30. Tradtrantip L, Jin BJ, Yao X, et al. Aquaporin-targeted therapeutics: state-of-the-field[J]. Adv Exp Med Biol, 2017, 969: 239-250. DOI: 10.1007/978-94-024-1057-0_16.
31. Ratelade J, Bennett JL, Verkman AS. Intravenous neuromyelitis optica autoantibody in mice targets aquaporin-4 in peripheral organs and area postrema[J/OL]. PLoS One, 2011, 6 (11): 27412[2011-11-04]. https://doi.org/10.1371/journal.pone.0027412. DOI: 10.1371/journal.pone.0027412.
32. Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica[J]. Proc Natl Acad Sci USA, 2011, 108(9): 3701-3706. DOI: 10.1073/pnas.1017385108.
33. Zhang H, Verkman AS. Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59[J]. J Autoimmun, 2014, 53: 67-77. DOI: 10.1016/j.jaut.2014.02.011.
34. Macedo AC, Isaac L. Systemic lupus erythematosus and deficiencies of early components of the complement classical pathway[J]. Front Immunol, 2016, 7: 55. DOI: 10.3389/fimmu.2016.00055.
35. Tüzün E, Kürtüncü M, Türkoğlu R, et al. Enhanced complement consumption in neuromyelitis optica and Behçet’s disease patients[J]. J Neuroimmunol, 2011, 233(1-2): 211-215. DOI: 10.1016/j.jneuroim.2010.11.010.
36. Kuroda H, Fujihara K, Takano R, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica[J]. J Neuroimmunol, 2013, 254(1-2): 178-182. DOI: 10.1016/j.jneuroim.2012.09.002.
37. Nytrova P, Potlukova E, Kemlink D, et al. Complement activation in patients with neuromyelitis optica[J]. J Neuroimmunol, 2014, 274(1-2): 185-191. DOI: 10.1016/j.jneuroim.2014.07.001.
38. Lubbers R,van Essen MF,van Kooten C,et al. Production of complement components by cells of the immune system[J]. Clin Exp Immunol, 2017, 188(2): 183-194. DOI: 10.1111/cei.12952.
39. Chen Y, Li R, Wu AM, et al. The complement and immunoglobulin levels in NMO patients[J]. Neurol Sci, 2014, 35(2): 215-220. DOI: 10.1007/s10072-013-1481-y.
40. Phuan PW, Zhang H, Asavapanumas N, et al. C1q-targeted monoclonal antibody prevents complement dependent cytotoxicity and neuropathology in in vitro and mouse models of neuromyelitis optica[J]. Acta Neuropathol, 2013, 125(6): 829-840. DOI: 10.1007/s00401-013-1128-3.
41. Tradtrantip L, Asavapanumas N, Phuan PW, et al. Potential therapeutic benefit of C1-esterase inhibitor in neuromyelitis optica evaluated in vitro and in an experimental rat model [J/OL]. PLoS One, 2014, 9(9): 106824[2014-09-05]. https://doi.org/10.1371/journal.pone.0106824. DOI: 10.1371/journal.pone.0106824.
42. van Beek J, Nicole O, Ali C, et al. Complement anaphylatoxin C3a is selectively protective against NMDA-induced neuronal cell death[J]. Neuroreport, 2001, 12(2): 289-293. DOI: 10.1097/00001756-200102120-00022.
43. Uzawa A, Mori M, Sawai S, et al. Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks[J]. Clin Chim Acta, 2013, 421: 181-183. DOI: 10.1016/j.cca.2013.03.020.
44. Woodruff TM, Nandakumar KS, Tedesco F. Inhibiting the C5-C5a receptor axis[J]. Mol Immunol, 2011, 48(14): 1631-642. DOI: 10.1016/j.molimm.2011.04.014.
45. Pittock SJ, Lennon VA, McKeon A, et al. Eculizumab in □AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study[J]. Lancet Neurol, 2013, 12(6): 554-562. DOI: 10.1016/S1474-4422(13)70076-0.

Chinese Journal of Ocular Fundus Diseases

The role of complement signaling pathway in the pathogenesis of neuromyelitis optica

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