The role of complement in neurological and neuropsychiatric diseases

Expert Review of Clinical Immunology

Volumn 11, Issue 10, 2015, Pages 1109-1119

  Morgan, Bryan Paul ^a  

^a CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

complement; demyelination; inflammation; neurodegeneration; neuropsychiatry

Indexed keywords

COMPLEMENT;

BRAIN INJURY; COMPLEMENT ACTIVATION; HUMAN; MENTAL DISEASE; NEUROLOGIC DISEASE; NEUROPSYCHIATRIC DISEASE; NONHUMAN; PROTEIN FUNCTION; REVIEW; ANIMAL; CENTRAL NERVOUS SYSTEM; IMMUNOLOGY; INFLAMMATION; INNATE IMMUNITY; PERIPHERAL NERVOUS SYSTEM; PHYSIOLOGY;

ANIMALS; CENTRAL NERVOUS SYSTEM; COMPLEMENT SYSTEM PROTEINS; HUMANS; IMMUNITY, INNATE; INFLAMMATION; NERVOUS SYSTEM DISEASES; PERIPHERAL NERVOUS SYSTEM;

EID: 84942119609     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/1744666X.2015.1074039     Document Type: Review

References (119)

1. Singhrao SK, Neal JW, Rushmere NK, et al. Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. Am J Pathol 2000;157:905-18
2. Gasque P, Neal JW, Singhrao SK, et al. Roles of the complement system in human neurodegenerative disorders: pro-inflammatory and tissue remodeling activities. Mol Neurobiol 2002;25:1-17
3. Berrih-Aknin S. Myasthenia Gravis: paradox versus paradigm in autoimmunity. J Autoimmun 2014;52:1-28
4. Ha JC, Richman DP. Myasthenia gravis and related disorders: Pathology and molecular pathogenesis. Biochim Biophys Acta 2015;1852:651-7
5. Nakano S, Engel AG. Myasthenia gravis: quantitative immunocytochemical analysis of inflammatory cells and detection of complement membrane attack complex at the end-plate in 30 patients. Neurology 1993;43:1167-72
6. Tüzün E, Christadoss P. Complement associated pathogenic mechanisms in myasthenia gravis. Autoimmun Rev 2013;12:904-11
7. Kusner LL, Kaminski HJ. The role of complement in experimental autoimmune myasthenia gravis. Ann NY Acad Sci 2012;1274:127-32
8. Piddlesden SJ, Jiang S, Levin JL, et al. Soluble complement receptor 1 (sCR1) protects against experimental autoimmune myasthenia gravis. J Neuroimmunol 1996;71:173-7
9. Morgan BP, Chamberlain-Banoub J, Neal JW, et al. The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in mice. Clin Exp Immunol 2006;146:294-302
10. Chamberlain-Banoub J, Neal JW, Mizuno M, et al. Complement membrane attack is required for endplate damage and clinical disease in passive experimental myasthenia gravis in Lewis rats. Clin Exp Immunol 2006;146:278-86
11. Maddison P. Treatment in Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci 2012;1275:78-84
12. Farrugia ME, Vincent A. Autoimmune mediated neuromuscular junction defects. Curr Opin Neurol 2010;23:489-95
13. Willison HJ. The immunobiology of Guillain-Barre syndromes. J Peripher Nerv Syst 2005;10:94-112
14. Willison HJ, Goodyear CS. Glycolipid antigens and autoantibodies in autoimmune neuropathies. Trends Immunol 2013;34: 453-9
15. Kuwabara S, Yuki N. Axonal guillain-barre syndrome: concepts and controversies. Lancet Neurol 2013;12:1180-8
16. van Doorn PA. What's new in Guillain-Barre syndrome in 2007-2008? J Peripher Nerv Syst 2009;14:72-4
17. Jung S, Toyka KV, Hartung HP. Soluble complement receptor type 1 inhibits experimental autoimmune neuritis in Lewis rats. Neurosci Lett 1995;200:167-70
18. Willison HJ, Halstead SK, Beveridge E, et al. The role of complement and complement regulators in mediating motor nerve terminal injury in murine models of Guillain-Barre syndrome. J Neuroimmunol 2008;201-202:172-82
19. Halstead SK, O'Hanlon GM, Humphreys PD, et al. Anti-disialoside antibodies kill perisynaptic Schwann cells and damage motor nerve terminals via membrane attack complex in a murine model of neuropathy. Brain 2004;127: 2109-23
20. Baxter DG. Serum complement in multiple sclerosis. A report of a study in 47 cases. Neurology 1963;13:869-72
21. Cerf JA, Carels G. Multiple sclerosis: serum factor producing reversible alterations in bioelectric responses. Science 1966; 152(3725):1066-8
22. Laurell AB, Link H. Complement-fixing antibrain antibodies in multiple sclerosis. A preliminary report. Acta Neurol Scand 1972;48:461-6
23. Lucchinetti C, Brück W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-17
24. Ingram G, Loveless S, Howell OW, et al. Complement activation in multiple sclerosis plaques: An immunohistochemical analysis. Acta Neuropathol Commun 2014;2:53
25. Ingram G, Hakobyan S, Hirst CL, et al. Systemic complement profiling in multiple sclerosis as a biomarker of disease state. Mult Scler 2012;18:1401-11
26. Schirmer L, Srivastava R, Hemmer B. To look for a needle in a haystack: the search for autoantibodies in multiple sclerosis. Mult Scler 2014;20:271-9
27. Srivastava R, Aslam M, Kalluri SR, et al. Potassium channel KIR4.1 as an immune target in multiple sclerosis. N Engl J Med 2012;367:115-23
28. Nerrant E, Salsac C, Charif M, et al. Lack of confirmation of anti-inward rectifying potassium channel 4.1 antibodies as reliable markers of multiple sclerosis. Mult Scler 2014;20:1699-703
29. Mead RJ, Singhrao SK, Neal JW, et al. The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. J Immunol 2002;168: 458-65
30. Mead RJ, Neal JW, Griffiths MR, et al. Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis. Lab Invest 2004;84:21-8
31. Ramaglia V, Jackson SJ, Hughes TR, et al. Complement activation and expression during chronic relapsing experimental autoimmune encephalomyelitis in the Biozzi ABH mouse. Clin Exp Immunol 2015;180: 432-41
32. Pereira WL, Reiche EM, Kallaur AP, Kaimen-Maciel DR. Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review. J Neurol Sci 2015;355:7-17
33. Nytrova P, Potlukova E, Kemlink D, et al. Complement activation in patients with neuromyelitis optica. J Neuroimmunol 2014;274:185-91
34. Bradl M, Lassmann H. Experimental models of neuromyelitis optica. Brain Pathol 2014;24:74-82
35. 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. Acta Neuropathol 2013;125:829-40
36. Zhang H, Verkman AS. Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59. J Autoimmun 2014;53:67-77
37. Wandinger KP, Saschenbrecker S, et al. Anti-NMDA-receptor encephalitis: A severe, multistage, treatable disorder presenting with psychosis. J Neuroimmunol 2011;231: 86-91
38. Bien CG, Bauer J. Autoimmune epilepsies. Neurotherapeutics 2014;11:311-18
39. Carvajal-González A, Leite MI, Waters P, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain 2014;137:2178-92
40. Lim GP, Yang F, Chu T, et al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 2000;20: 5709-14
41. Aisen PS, Davis KL. Inflammatory mechanisms in Alzheimer's disease: implications for therapy. Am J Psychiatry 1994;151:1105-13
42. Mosher KI, Wyss-Coray T. Microglial dysfunction in brain aging and Alzheimer's disease. Biochem Pharmacol 2014;88: 594-604
43. Eikelenboom P, Stam FC. Immunoglobulins and complement factors in senile plaques. An immunoperoxidase study. Acta Neuropathol 1982;57:239-42
44. Ishii T, Haga S. Immuno-electron-microscopic localization of complement in amyloid fibrils of senile plaques. Acta Neuropathol 1984;63:296-300
45. McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 1995;21:195-218
46. McGeer PL, Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. Neurology 1992;42: 447-9
47. Fonseca MI, Zhou J, Botto M, Tenner AJ. Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J Neurosci 2004;24:6457-65
48. Wyss-Coray T, Yan F, Lin AH, et al. Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice. Proc Natl Acad Sci USA 2002;99:10837-42
49. Maier M, Peng Y, Jiang L, et al. Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J Neurosci 2008;28:6333-41
50. Crehan H, Holton P, Wray S, et al. Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology 2012;217:244-50
51. Frey KA, Petrou M. Imaging amyloidopathy in Parkinson disease and Parkinsonian dementia syndromes. Clin Transl Imaging 2015;3:57-64
52. Reid WG, Hely MA, Morris JG, et al. Dementia in Parkinson's disease: A 20-year neuropsychological study (Sydney Multicentre Study). J Neurol Neurosurg Psychiatry 2011;82:1033-7
53. More SV, Kumar H, Kim IS, et al. Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson's disease. Mediators Inflamm 2013;2013:952375
54. Goldknopf IL, Sheta EA, Bryson J, et al. Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease. Biochem Biophys Res Commun 2006;342:1034-9
55. Wang Y, Hancock AM, Bradner J, et al. Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy. Am J Pathol 2011;178:1509-16
56. More SV, Kumar H, Kim IS, et al. Strategic selection of neuroinflammatory models in Parkinson's disease: evidence from experimental studies. CNS Neurol Disord Drug Targets 2013;12:680-97
57. Hovden H, Frederiksen JL, Pedersen SW. Immune system alterations in amyotrophic lateral sclerosis. Acta Neurol Scand 2013;128:287-96
58. Woodruff TM, Costantini KJ, Taylor SM, Noakes PG. Role of complement in motor neuron disease: Animal models and therapeutic potential of complement inhibitors. Adv Exp Med Biol 2008;632: 143-58
59. Mantovani S, Gordon R, Macmaw JK, et al. Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood. J Neuroimmunol 2014;276: 213-18
60. Heurich B, El Idrissi NB, et al. Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis. J Neuroimmunol 2011;235:104-9
61. Lobsiger CS, Boillee S, Pozniak C, et al. C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice. Proc Natl Acad Sci USA 2013;110:E4385-92
62. Lozano D, Gonzales-Portillo GS, Acosta S, et al. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr Dis Treat 2015;11:97-106
63. Bellander B-M, Singhrao SK, Ohlsson M, et al. Complement activation in the human brain after traumatic head injury. J Neurotrauma 2001;18:1295-311
64. Stahel PF, Morganti-Kossmann MC, Kossmann T. The role of the complement system in traumatic brain injury. Brain Res Brain Res Rev 1998;27:243-56
65. Stahel PF, Morganti-Kossmann MC, Perez D, et al. Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury. J Neurotrauma 2001;18:773-81
66. Stahel PF, Flierl MA, Morgan BP, et al. Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. J Neuroinflammation 2009;6:2
67. Leinhase I, Schmidt OI, Thurman JM, et al. Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Exp Neurol 2006;199:454-64
68. Fluiter K, Opperhuizen AL, Morgan BP, et al. Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. J Immunol 2014;192: 2339-48
69. Leinhase I, Rozanski M, Harhausen D, et al. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: A randomized placebo-controlled study in mice. J Neuroinflammation 2007;4:13
70. Longhi L, Perego C, Ortolano F, et al. C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice. Crit Care Med 2009;37:659-65
71. Li Y, Chavko M, Slack JL, et al. Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats. Acta Neuropathol Commun 2013;1(1):52
72. Anderson A, Robert S, Huang W, et al. Activation of complement pathways after contusion-induced spinal cord injury. J Neurotrauma 2004;21:1831-46
73. Qiao F, Atkinson C, Song H, et al. Complement plays an important role in spinal cord injury and represents a therapeutic target for improving recovery following trauma. Am J Pathol 2006;169: 1039-47
74. Guo Q, Li S, Liang Y, et al. Effects of C3 deficiency on inflammation and regeneration following spinal cord injury in mice. Neurosci Lett 2010;485:32-6
75. Reynolds DN, Smith SA, Zhang YP, et al. Vaccinia virus complement control protein reduces inflammation and improves spinal cord integrity following spinal cord injury. Ann NY Acad Sci 2004;1035:165-78
76. Li LM, Li JB, Zhu Y, Fan GY. Soluble complement receptor type 1 inhibits complement system activation and improves motor function in acute spinal cord injury. Spinal Cord 2009;48:105-11
77. Ramaglia V, Tannemaat MR, de Kok M, et al. Complement inhibition accelerates regeneration in a model of peripheral nerve injury. Mol Immunol 2009;47:302-9
78. Gorsuch WB, Chrysanthou E, Schwaeble WJ, Stahl GL. The complement system in ischemia-reperfusion injuries. Immunobiology 2012;217:1026-33
79. D'Ambrosio AL, Pinsky DJ, Connolly ES. The role of the complement cascade in ischemia/reperfusion injury: implications for neuroprotection. Mol Med 2001;7:367-82
80. Storini C, Rossi E, Marrella V, et al. C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation. Neurobiol Dis 2005;19:10-17
81. Heydenreich N, Nolte MW, Göb E, et al. C1-inhibitor protects from brain ischemia-reperfusion injury by combined antiinflammatory and antithrombotic mechanisms. Stroke 2012;43:2457-67
82. Costa C, Zhao L, Shen Y, et al. Role of complement component C5 in cerebral ischemia/reperfusion injury. Brain Res 2006;1100:142-51
83. Harhausen D, Khojasteh U, Stahel PF, et al. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice. J Neuroinflammation 2010;7:15
84. Lassiter HA. The role of complement in neonatal hypoxic-ischemic cerebral injury. Clin Perinatol 2004;31:117-27
85. Skattum L, van Deuren M, van der Poll T, Truedsson L. Complement deficiency states and associated infections. Mol Immunol 2011;48:1643-55
86. Adriani KS, Brouwer MC, Geldhoff M, et al. Common polymorphisms in the complement system and susceptiblity to bacterial meningitis. J Infect 2013;66: 255-62
87. Stoiber H, Kacani L, Speth C, et al. The supportive role of complement in HIV pathogenesis. Immunol Rev 2001;180: 168-76
88. Klein MA, Kaeser PS, Schwarz P, et al. Complement facilitates early prion pathogenesis. Nat Med 2001;7:488-92
89. Speth C, Williams K, Hagleitner M, et al. Complement synthesis and activation in the brain of SIV-infected monkeys. J Neuroimmunol 2004;151:45-54
90. Jacob A, Hensley LK, Safratowich BD, et al. The role of the complement cascade in endotoxin-induced septic encephalopathy. Lab Invest 2007;87:1186-94
91. Bahia El Idrissi N, Das PK, et al.. M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator. Acta Neuropathol 2015;129:653-67
92. Popescu A, Kao AH. Neuropsychiatric systemic lupus erythematosus. Curr Neuropharmacol 2011;9:449-57
93. Levite M, Ganor Y. Autoantibodies to glutamate receptors can damage the brain in epilepsy, systemic lupus erythematosus and encephalitis. Expert Rev Neurother 2008;8: 1141-60
94. Sanders ME, Alexander EL, et al. Detection of activated terminal complement (C5b-9) in cerebrospinal fluid from patients with central nervous system involvement of primary Sjogren's syndrome or systemic lupus erythematosus. J Immunol 1987;138: 2095-9
95. Maes M. A review on the acute phase response in major depression. Rev Neurosci 1993;4:407-16
96. Corcos M, Guilbaud O, Hjalmarsson L, et al. Cytokines and depression: An analogic approach. Biomed Pharmacother 2002;56: 105-10
97. Leonard BE. Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 2014;48:261-7
98. Berk M, Williams LJ, Jacka FN, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 2013;11:200
99. Setiawan E, Wilson AA, Mizrahi R, et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 2015;72:268-75
100. Ramaglia V, Hughes TR, Donev RM, et al. C3-dependent mechanism of microglial priming relevant to multiple sclerosis. Proc Natl Acad Sci USA 2012;109:965-70
101. Jones AL, Mowry BJ, Pender MP, Greer JM. Immune dysregulation and self-reactivity in schizophrenia: Do some cases of schizophrenia have an autoimmune basis? Immunol Cell Biol 2005;83:9-17
102. Rothenmundt M, Arolt V, Bayer TA. Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun 2001;15:319-39
103. Spivak B, Radwan M, Brandon J, et al. Reduced total complement haemolytic activity in schizophrenic patients. Psychol Med 1993;23:315-18
104. Mayilyan KR, Arnold JN, Presanis JS, et al. Increased complement classical and mannan-binding lectin pathway activities in schizophrenia. Neurosci Lett 2006;404: 336-41
105. Hakobyan S, Boyajyan A, Sim RB. Classical pathway complement activity in schizophrenia. Neurosci Lett 2005;374:35-7
106. Li Y, Zhou K, Zhang Z, et al. Label-free quantitative proteomic analysis reveals dysfunction of complement pathway in peripheral blood of schizophrenia patients: evidence for the immune hypothesis of schizophrenia. Mol Biosyst 2012;8:2664-71
107. Rudduck C, Beckman L, Franzen G, Lindström L. C3 and C6 complement types in schizophrenia. Hum Hered 1985;35: 255-8
108. Fananás L, Moral P, Panadero MA, Bertranpetit J. Complement genetic markers in schizophrenia: C3, BF and C6 polymorphisms. Hum Hered 1992;42: 162-7
109. Rudduck C, Franzen G, Hansson A, Rorsman B. Properdin factor B (Bf) types in schizophrenia. Hum Hered 1984;34: 331-3
110. Schroers R, Nöthen MM, Rietschel M, et al. Investigation of complement C4B deficiency in schizophrenia. Hum Hered 1997;47:279-82
111. Alokam R, Singhal S, Srivathsav GS, et al. Design of dual inhibitors of ROCK-I and NOX2 as potential leads for the treatment of neuroinflammation associated with various neurological diseases including autism spectrum disorder. Mol Biosyst 2015;11:607-17
112. Zayats T, Athanasiu L, Sonderby I, et al. Genome-Wide analysis of attention deficit hyperactivity disorder in Norway. PLoS One 2015;10(4):e0122501
113. Mitchell RH, Goldstein BI. Inflammation in children and adolescents with neuropsychiatric disorders: A systematic review. J Am Acad Child Adolesc Psychiatry 2014;53:274-96
114. Bronson SL, Bale TL. Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal anti-inflammatory treatment. Endocrinology 2014;155:2635-46
115. Stephan AH, Barres BA, Stevens B. The complement system: An unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 2012;35:369-89
116. Howard JF Jr, Barohn RJ, Cutter GR, et al. MG Study Group. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve 2013;48:76-84
117. Pittock SJ, Lennon VA, McKeon A, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: An open-label pilot study. Lancet Neurol 2013;12:554-62
118. Ricklin D, Lambris JD. Progress and trends in complement therapeutics. Adv Exp Med Biol 2013;735:1-22
119. Inhibition of complement activation (Eculizumab) in Guillain-Barre syndrome study (ICA-GBS). Available from: https:// clinicaltrials.gov/ct2/show/NCT02029378