视神经脊髓炎免疫学发病机制研究进展
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摘要
近年来,由于在视神经脊髓炎(NMO)中发现了特异性抗体-抗水通道蛋白抗体,学者开始重视对NMO的研究。随着研究的不断深入,人们对NMO发病机制的了解也日益增多,目前认为,NMO的发病是基因、免疫机制、环境等多种影响因素共同作用的结果,其中免疫系统在NMO的发生、发展中具有重要作用。免疫系统是一个复杂的大网络,各部分之间的相互协调是维持机体正常稳态的关键,任何一个环节的破坏均可能会引起免疫平衡的打破。该文从抗体、补体、免疫细胞的角度就NMO的免疫学发病机制研究进展作一综述。
Recently,researchers have begun to pay attention to the study of neuromyelitis optica(NMO)due to the discovery of the specific antibody-anti-aquaporin antibodies.With the deepening of research,understanding of the pathogenesis of NMO is increasing.It is believed that the pathogenesis of NMO is the consequence of the combined effect of genes,immune mechanisms and environment.Among them,the immune system is the most impotant role.The immune system is a large complex network,The coordination of which is the key to maintaining the homeostasis of body.And the destruction of any link might break the balance of immune system.In the present review,we will summarize the research progress of immunological pathogenesis of NMO from the perspective of antibody,complement and immune cells.
Recently,researchers have begun to pay attention to the study of neuromyelitis optica(NMO)due to the discovery of the specific antibody-anti-aquaporin antibodies.With the deepening of research,understanding of the pathogenesis of NMO is increasing.It is believed that the pathogenesis of NMO is the consequence of the combined effect of genes,immune mechanisms and environment.Among them,the immune system is the most impotant role.The immune system is a large complex network,The coordination of which is the key to maintaining the homeostasis of body.And the destruction of any link might break the balance of immune system.In the present review,we will summarize the research progress of immunological pathogenesis of NMO from the perspective of antibody,complement and immune cells.
引文
[1] HARDY T A,REDDEL S W,BARNETT M H,et al.Atypical inflammatory demyelinating syndromes of the CNS[J].Lancet Neurol,2016,15(9):967-981.
[2]JARIUS S,WILDEMANN B.The history of neuromyelitis optica[J].J Neuroinflammation,2013,10(6):8.
[3] MASAKI K.Molecular pathology of multiple sclerosis and neuromyelitis optica[J].Nihon Rinsho,2014,72(11):1909-1917.
[4] PAPADOPOULOS M C,VERKMAN A S.Aquaporin water channels in the nervous system[J].Nat Rev Neurosci,2013,14(4):265-277.
[5] LENNON V A,WINGERCHUK D M,KRYZER T J,et al.A serum autoantibody marker of neuromyelitis optica:distinction from multiple sclerosis[J].Lancet,2004,364(9451):2106-2112.
[6] WINGERCHUK D M,LENNON V A,PITTOCK S J,et al.Revised diagnostic criteria for neuromyelitis optica[J].Neurology,2006,66(10):1485-1489.
[7]JACOB A,MCKEON A,NAKASHIMA I,et al.Current concept of neuromyelitis optica(NMO)and NMO spectrum disorders[J].J Neurol Neurosurg Psychiatry,2013,84(8):922-930.
[8] HINSON S R,MCKEON A,LENNON V A.Neurological autoimmunity targeting aquaporin-4[J].Neuroscience,2010,168(4):1009-1018.
[9] RATELADE J,BENNETT J L,VERKMAN A S.Evidence against cellular internalization in vivo of NMO-IgG,aquaporin-4,and excitatory amino acid transporter 2in neuromyelitis optica[J].J Biol Chem,2011,286(52):45156-45164.
[10]ASGARI N,SKEJOE H P,LILLEVANG S T,et al.Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica(NMO):a population-based,descriptive study[J].BMC Neurol,2013,13(3):33.
[11]CHANSON J B,ALAME M,COLLONGUES N,et al.Evaluation of clinical interest of anti-aquaporin-4autoantibody followup in neuromyelitis optica[J].Clin Dev Immunol,2013,2013:146219.
[12]ZHAO C,LI H Z,ZHAO D D,et al.Increased circulating T follicular helper cells are inhibited by rituximab in neuromyelitis optica spectrum disorder[J].Front Neurol,2017,8:104.
[13]SAADOUN S,WATERS P,BELL B A,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.
[14]LIU Y,HARLOW D E,GIVEN K S,et al.Variable sensitivity to complement-dependent cytotoxicity in murine models of neuromyelitis optica[J].J Neuroinflammation,2016,13(1):301.
[15]TRADTRANTIP L,YAO X,SU T,et al.Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica[J].Acta Neuropathol,2017,134(1):35-44.
[16]CHEN Y,LI R,WU A M,et al.The complement and immunoglobulin levels in NMO patients[J].Neurol Sci,2014,35(2):215-220.
[17]RATELADE J,ZHANG H,SAADOUN S,et al.Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss[J].Acta Neuropathol,2012,123(6):861-872.
[18]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.
[19]NISHIYAMA S,MISU T,NURIYA M,et al.Complement-dependent and-independent aquaporin 4-antibodymediated cytotoxicity in human astrocytes:Pathogenetic implications in neuromyelitis optica[J].Biochem Biophys Rep,2016,7(1):45-51.
[20]POHL M,FISCHER M T,MADER S,et al.Pathogenic T cell responses against aquaporin 4[J].Acta Neuropathol,2011,122(1):21-34.
[21]JONES M V,HUANG H,CALABRESI P A,et al.Pathogenic aquaporin-4reactive T cells are sufficient to induce mouse model of neuromyelitis optica[J].Acta Neuropathol Commun,2015,3(3):28.
[22]BARROS P O,CASSANO T,HYGINO J,et al.Prediction of disease severity in neuromyelitis optica by the levels of interleukin(IL)-6produced during remission phase[J].Clin Exp Immunol,2016,183(3):480-489.
[23]DOS PASSOS G R,SATO D K,BECKER J,et al.Th17cells pathways in multiple sclerosis and neuromyelitis optica spectrum disorders:pathophysiological and therapeutic implications[J].Mediators Inflamm,2016,2016:5314541.
[24]UENO H,BANCHEREAU J,VINUESA C G.Pathophysiology of T follicular helper cells in humans and mice[J].Nat Immunol,2015,16(2):142-152.
[25]VINUESA C G,LINTERMAN M A,YU D,et al.Follicular Helper T Cells[J].Annu Rev Immunol,2016,34(4):335-368.
[26]LI Y J,ZHANG F,QI Y,et al.Association of circulating follicular helper T cells with disease course of NMO spectrum disorders[J].J Neuroimmunol,2015,278(3):239-246.
[27]KRISHNAMOORTHY G,LASSMANN H,WEKERLE H,et al.Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation[J].J Clin Invest,2006,116(9):2385-2392.
[28]VARRIN-DOYER M,SPENCER C M,SCHULZE-TOPPHOFF U,et al.Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17bias and recognize Clostridium ABC transporter[J].Ann Neurol,2012,72(1):53-64.
[29]KONG B S,KIM Y,KIM G Y,et al.Increased frequency of IL-6-producing non-classical monocytes in neuromyelitis optica spectrum disorder[J].J Neuroinflammation,2017,14(1):191.
[30]SAADOUN S,BRIDGES L R,VERKMAN A S,et al.Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions[J].Neuroreport,2012,23(18):1044-1047.
[31]PAPADOPOULOS M C,BENNETT J L,VERKMAN A S.Treatment of neuromyelitis optica:state-of-the-art and emerging therapies[J].Nat Rev Neurol,2014,10(9):493-506.
[32]MICHAEL B D,ELSONE L,GRIFFITHS M J,et al.Post-acute serum eosinophil and neutrophil-associated cytokine/chemokine profile can distinguish between patients with neuromyelitis optica and multiple sclerosis;and identifies potential pathophysiological mechanisms-a pilot study[J].Cytokine,2013,64(1):90-96.
[33]ZHANG H,VERKMAN A S.Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica[J].J Clin Invest,2013,123(5):2306-2316.
[2]JARIUS S,WILDEMANN B.The history of neuromyelitis optica[J].J Neuroinflammation,2013,10(6):8.
[3] MASAKI K.Molecular pathology of multiple sclerosis and neuromyelitis optica[J].Nihon Rinsho,2014,72(11):1909-1917.
[4] PAPADOPOULOS M C,VERKMAN A S.Aquaporin water channels in the nervous system[J].Nat Rev Neurosci,2013,14(4):265-277.
[5] LENNON V A,WINGERCHUK D M,KRYZER T J,et al.A serum autoantibody marker of neuromyelitis optica:distinction from multiple sclerosis[J].Lancet,2004,364(9451):2106-2112.
[6] WINGERCHUK D M,LENNON V A,PITTOCK S J,et al.Revised diagnostic criteria for neuromyelitis optica[J].Neurology,2006,66(10):1485-1489.
[7]JACOB A,MCKEON A,NAKASHIMA I,et al.Current concept of neuromyelitis optica(NMO)and NMO spectrum disorders[J].J Neurol Neurosurg Psychiatry,2013,84(8):922-930.
[8] HINSON S R,MCKEON A,LENNON V A.Neurological autoimmunity targeting aquaporin-4[J].Neuroscience,2010,168(4):1009-1018.
[9] RATELADE J,BENNETT J L,VERKMAN A S.Evidence against cellular internalization in vivo of NMO-IgG,aquaporin-4,and excitatory amino acid transporter 2in neuromyelitis optica[J].J Biol Chem,2011,286(52):45156-45164.
[10]ASGARI N,SKEJOE H P,LILLEVANG S T,et al.Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica(NMO):a population-based,descriptive study[J].BMC Neurol,2013,13(3):33.
[11]CHANSON J B,ALAME M,COLLONGUES N,et al.Evaluation of clinical interest of anti-aquaporin-4autoantibody followup in neuromyelitis optica[J].Clin Dev Immunol,2013,2013:146219.
[12]ZHAO C,LI H Z,ZHAO D D,et al.Increased circulating T follicular helper cells are inhibited by rituximab in neuromyelitis optica spectrum disorder[J].Front Neurol,2017,8:104.
[13]SAADOUN S,WATERS P,BELL B A,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.
[14]LIU Y,HARLOW D E,GIVEN K S,et al.Variable sensitivity to complement-dependent cytotoxicity in murine models of neuromyelitis optica[J].J Neuroinflammation,2016,13(1):301.
[15]TRADTRANTIP L,YAO X,SU T,et al.Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica[J].Acta Neuropathol,2017,134(1):35-44.
[16]CHEN Y,LI R,WU A M,et al.The complement and immunoglobulin levels in NMO patients[J].Neurol Sci,2014,35(2):215-220.
[17]RATELADE J,ZHANG H,SAADOUN S,et al.Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss[J].Acta Neuropathol,2012,123(6):861-872.
[18]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.
[19]NISHIYAMA S,MISU T,NURIYA M,et al.Complement-dependent and-independent aquaporin 4-antibodymediated cytotoxicity in human astrocytes:Pathogenetic implications in neuromyelitis optica[J].Biochem Biophys Rep,2016,7(1):45-51.
[20]POHL M,FISCHER M T,MADER S,et al.Pathogenic T cell responses against aquaporin 4[J].Acta Neuropathol,2011,122(1):21-34.
[21]JONES M V,HUANG H,CALABRESI P A,et al.Pathogenic aquaporin-4reactive T cells are sufficient to induce mouse model of neuromyelitis optica[J].Acta Neuropathol Commun,2015,3(3):28.
[22]BARROS P O,CASSANO T,HYGINO J,et al.Prediction of disease severity in neuromyelitis optica by the levels of interleukin(IL)-6produced during remission phase[J].Clin Exp Immunol,2016,183(3):480-489.
[23]DOS PASSOS G R,SATO D K,BECKER J,et al.Th17cells pathways in multiple sclerosis and neuromyelitis optica spectrum disorders:pathophysiological and therapeutic implications[J].Mediators Inflamm,2016,2016:5314541.
[24]UENO H,BANCHEREAU J,VINUESA C G.Pathophysiology of T follicular helper cells in humans and mice[J].Nat Immunol,2015,16(2):142-152.
[25]VINUESA C G,LINTERMAN M A,YU D,et al.Follicular Helper T Cells[J].Annu Rev Immunol,2016,34(4):335-368.
[26]LI Y J,ZHANG F,QI Y,et al.Association of circulating follicular helper T cells with disease course of NMO spectrum disorders[J].J Neuroimmunol,2015,278(3):239-246.
[27]KRISHNAMOORTHY G,LASSMANN H,WEKERLE H,et al.Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation[J].J Clin Invest,2006,116(9):2385-2392.
[28]VARRIN-DOYER M,SPENCER C M,SCHULZE-TOPPHOFF U,et al.Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17bias and recognize Clostridium ABC transporter[J].Ann Neurol,2012,72(1):53-64.
[29]KONG B S,KIM Y,KIM G Y,et al.Increased frequency of IL-6-producing non-classical monocytes in neuromyelitis optica spectrum disorder[J].J Neuroinflammation,2017,14(1):191.
[30]SAADOUN S,BRIDGES L R,VERKMAN A S,et al.Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions[J].Neuroreport,2012,23(18):1044-1047.
[31]PAPADOPOULOS M C,BENNETT J L,VERKMAN A S.Treatment of neuromyelitis optica:state-of-the-art and emerging therapies[J].Nat Rev Neurol,2014,10(9):493-506.
[32]MICHAEL B D,ELSONE L,GRIFFITHS M J,et al.Post-acute serum eosinophil and neutrophil-associated cytokine/chemokine profile can distinguish between patients with neuromyelitis optica and multiple sclerosis;and identifies potential pathophysiological mechanisms-a pilot study[J].Cytokine,2013,64(1):90-96.
[33]ZHANG H,VERKMAN A S.Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica[J].J Clin Invest,2013,123(5):2306-2316.