重症肌无力的免疫机制研究进展
摘要
<正>重症肌无力(myasthenia gravis,MG)是依赖细胞免疫并由抗乙酰胆碱受体抗体(anti-acetyl-choline receptor antibody,anti-AChRAb)介导、补体参与导致神经肌肉接头(neuromuscular junc-tion,NMJ)处传递障碍的获得性自身免疫病。
引文
[1]Chen Q,Kim YC,Laurence A,et al.IL-2controls the sta-bility of Foxp3expression in TGF-beta-induced Foxp3+Tcells in vivo[J].J Immunol,2011,186(11):6329-6337.
[2]Laurence A,Tato CM,Davidson TS,et al.Interleukin-2sig-naling via STAT5constrains T helper 17cell generation[J].Immunity,2007.26(3):371-381.
[3]Wang W,Milani M,Ostlie N,et al.C57BL/6mice genetical-ly deficient in IL-12/IL-23and IFN-gamma are susceptible toexperimental autoimmune myasthenia gravis,suggesting apathogenic role of non-Th1cells[J].J Immunol,2007,178(11):7072-7080.
[4]Prochazkova J,Pokorna K,Holan V.IL-12inhibits theTGF-beta-dependent T cell developmental programs andskews the TGF-beta-induced differentiation into a Th1-like di-rection[J].Immunobiology,2012,217(1):74-82.
[5]王志强,张志坚,吴立坚,等.重症肌无力患者外周血单个核细胞TNF-α和IL-6水平在疾病转归中的动态变化[J].中国神经免疫学和神经病学杂志,2009,16(2):90-93.
[6]Karachunski PI,Ostlie NS,Okita DK,et al.Interleukin-4deficiency facilitates development of experimental myastheniagravis and precludes its prevention by nasal administration ofCD4+epitope sequences of the acetylcholine receptor[J].JNeuroimmunol,1999,95:73-84.
[7]Sheng JR,Li L,Ganesh BB,et al.Suppression of experimen-tal autoimmune myasthenia gravis by granulocyte-macrophagecolony-stimulating factor is associated with an expansion ofFoxp3+regulatory T cells[J].J Immunol,2006,177(8):5296-5306.
[8]Poussin MA,Goluszko E,Franco JU,et al.Role of IL-5during primary and secondary immune response to acetylcho-line receptor[J].J Neuroimmunol,2002,125(1-2):51-58.
[9]Barr TA,Shen P,Brown S,et al.B cell depletion therapyameliorates autoimmune disease through ablation of IL-6-pro-ducing B cells[J].J Exp Med,2012,209(5):1001-1010.
[10]Chi LJ,Wang HB,Wang WZ.Impairment of circulatingCD4+CD25+regulatory T cells in patients with chronic in-flammatory demyelinating polyradiculoneuropathy[J].J Pe-ripher Nerv Syst,2008,13(1):54-63.
[11]Yoshimura A,Muto G.TGF-βfunction in immune suppres-sion[J].Curr Top Microbiol Immunol,2011,350:127-147.
[12]Adorini L.Cytokine-based immunointervention in the treat-ment of autoimmune diseases[J].Clin Exp Immunol,2003,132(2):185-192.
[13]Wan Q,Kozhaya L,ElHed A,et al.Cytokine signalsthrough PI-3kinase pathway modulate Th17cytokine pro-duction by CCR6+human memory T cells[J].J Exp Med,2011,208(9):1875-1887.
[14]Santarlasci V,Maggi L,Capone M,et al.Rarity of human Thelper 17cells is due to retinoic acid orphan receptor-depend-ent mechanisms that limit their expansion[J].Immunity,2012,36(2):201-214.
[15]Mu L,Sun B,Kong Q,et al.Disequilibrium of T helper type1,2and 17cells and regulatory T cells during the develop-ment of experimental autoimmune myasthenia gravis[J].Im-munology,2009,128(1Suppl):e826-836.
[16]Wang Z,Wang W,Chen Y,et al.T helper type 17cells ex-pand in patients with myasthenia-associated thymoma[J].Scand J Immunol,2012,76(1):54-61.
[17]Li X,Xiao BG,Xi JY,et al.Decrease of CD4(+)CD25(high)Foxp3(+)regulatory T cells and elevation of CD19(+)BAFF-R(+)B cells and soluble ICAM-1in myastheniagravis[J].Clin Immunol,2008,126(2):180-188.
[18]方琪,冉娟娟,蔡秀英,等.重症肌无力患者Foxp3+CD4+CD25+调节性T细胞与AChRAb、Titin-Ab的相关研究[J].中国神经免疫学和神经病学杂志,2010,17(5):342-344.
[19]Matsushita T,Yanaba K,Bouaziz JD,et al.Regulatory Bcells inhibit EAE initiation in mice while other B cells pro-mote disease progression[J].J Clin Invest,2008,118(10):3420-3430.
[20]Mizoguchi A,Bhan AK.A case for regulatory B cells[J].Jmmunol,2006,176(2):705-710.
[21]Yanaba K,Bouaziz JD,Haas KM,et al.A regulatory B cellsubset with a unique CD1dhiCD5+phenotype controls T cell-dependent inflammatory responses[J].Immunity,2008,28(5):639-650.
[22]Matsushita T,Horikawa M,Iwata Y,et al.Regulatory Bcells and regulatory T cells have independent roles in control-ling experimental autoimmune encephalomyelitis initiation andlate-phase immunopathogenesis[J].J Immunol,2010,185(4):2240-2252.
[23]Douglas RS,Woo EY,Capocasale RJ,et al.Altered re-sponse to and production of TGF-beta by B cells from autoim-mune NZB mice[J].Cell Immunol,1997,179(2):126-137.
[24]Zhang M,Li H,Guo J,et al.Different molecular expressionin thymoma with ocular or generalized myasthenia gravis[J].J Neurol Sci,2012,313(1-2):27-31.
[25]Shiao YM,Lee CC,Hsu YH,et al.Ectopic and high CX-CL13chemokine expression in myasthenia gravis with thymiclymphoid hyperplasia[J].J Neuroimmunol,2010,221(1-2):101-106.
[26]Kaminski HJ,Kusner LL,Richmonds C,et al.Deficiency ofdecay accelerating factor and CD59leads to crisis in experi-mental myasthenia[J].Exp Neurol,2006,202(2):287-293.
[27]Tüzün E,Scott BG,Goluszko E,et al.Genetic evidence forinvolvement of classical complement pathway in induction ofexperimental autoimmune myasthenia gravis[J].J Immunol,2003,171(7):3847-3854.
[2]Laurence A,Tato CM,Davidson TS,et al.Interleukin-2sig-naling via STAT5constrains T helper 17cell generation[J].Immunity,2007.26(3):371-381.
[3]Wang W,Milani M,Ostlie N,et al.C57BL/6mice genetical-ly deficient in IL-12/IL-23and IFN-gamma are susceptible toexperimental autoimmune myasthenia gravis,suggesting apathogenic role of non-Th1cells[J].J Immunol,2007,178(11):7072-7080.
[4]Prochazkova J,Pokorna K,Holan V.IL-12inhibits theTGF-beta-dependent T cell developmental programs andskews the TGF-beta-induced differentiation into a Th1-like di-rection[J].Immunobiology,2012,217(1):74-82.
[5]王志强,张志坚,吴立坚,等.重症肌无力患者外周血单个核细胞TNF-α和IL-6水平在疾病转归中的动态变化[J].中国神经免疫学和神经病学杂志,2009,16(2):90-93.
[6]Karachunski PI,Ostlie NS,Okita DK,et al.Interleukin-4deficiency facilitates development of experimental myastheniagravis and precludes its prevention by nasal administration ofCD4+epitope sequences of the acetylcholine receptor[J].JNeuroimmunol,1999,95:73-84.
[7]Sheng JR,Li L,Ganesh BB,et al.Suppression of experimen-tal autoimmune myasthenia gravis by granulocyte-macrophagecolony-stimulating factor is associated with an expansion ofFoxp3+regulatory T cells[J].J Immunol,2006,177(8):5296-5306.
[8]Poussin MA,Goluszko E,Franco JU,et al.Role of IL-5during primary and secondary immune response to acetylcho-line receptor[J].J Neuroimmunol,2002,125(1-2):51-58.
[9]Barr TA,Shen P,Brown S,et al.B cell depletion therapyameliorates autoimmune disease through ablation of IL-6-pro-ducing B cells[J].J Exp Med,2012,209(5):1001-1010.
[10]Chi LJ,Wang HB,Wang WZ.Impairment of circulatingCD4+CD25+regulatory T cells in patients with chronic in-flammatory demyelinating polyradiculoneuropathy[J].J Pe-ripher Nerv Syst,2008,13(1):54-63.
[11]Yoshimura A,Muto G.TGF-βfunction in immune suppres-sion[J].Curr Top Microbiol Immunol,2011,350:127-147.
[12]Adorini L.Cytokine-based immunointervention in the treat-ment of autoimmune diseases[J].Clin Exp Immunol,2003,132(2):185-192.
[13]Wan Q,Kozhaya L,ElHed A,et al.Cytokine signalsthrough PI-3kinase pathway modulate Th17cytokine pro-duction by CCR6+human memory T cells[J].J Exp Med,2011,208(9):1875-1887.
[14]Santarlasci V,Maggi L,Capone M,et al.Rarity of human Thelper 17cells is due to retinoic acid orphan receptor-depend-ent mechanisms that limit their expansion[J].Immunity,2012,36(2):201-214.
[15]Mu L,Sun B,Kong Q,et al.Disequilibrium of T helper type1,2and 17cells and regulatory T cells during the develop-ment of experimental autoimmune myasthenia gravis[J].Im-munology,2009,128(1Suppl):e826-836.
[16]Wang Z,Wang W,Chen Y,et al.T helper type 17cells ex-pand in patients with myasthenia-associated thymoma[J].Scand J Immunol,2012,76(1):54-61.
[17]Li X,Xiao BG,Xi JY,et al.Decrease of CD4(+)CD25(high)Foxp3(+)regulatory T cells and elevation of CD19(+)BAFF-R(+)B cells and soluble ICAM-1in myastheniagravis[J].Clin Immunol,2008,126(2):180-188.
[18]方琪,冉娟娟,蔡秀英,等.重症肌无力患者Foxp3+CD4+CD25+调节性T细胞与AChRAb、Titin-Ab的相关研究[J].中国神经免疫学和神经病学杂志,2010,17(5):342-344.
[19]Matsushita T,Yanaba K,Bouaziz JD,et al.Regulatory Bcells inhibit EAE initiation in mice while other B cells pro-mote disease progression[J].J Clin Invest,2008,118(10):3420-3430.
[20]Mizoguchi A,Bhan AK.A case for regulatory B cells[J].Jmmunol,2006,176(2):705-710.
[21]Yanaba K,Bouaziz JD,Haas KM,et al.A regulatory B cellsubset with a unique CD1dhiCD5+phenotype controls T cell-dependent inflammatory responses[J].Immunity,2008,28(5):639-650.
[22]Matsushita T,Horikawa M,Iwata Y,et al.Regulatory Bcells and regulatory T cells have independent roles in control-ling experimental autoimmune encephalomyelitis initiation andlate-phase immunopathogenesis[J].J Immunol,2010,185(4):2240-2252.
[23]Douglas RS,Woo EY,Capocasale RJ,et al.Altered re-sponse to and production of TGF-beta by B cells from autoim-mune NZB mice[J].Cell Immunol,1997,179(2):126-137.
[24]Zhang M,Li H,Guo J,et al.Different molecular expressionin thymoma with ocular or generalized myasthenia gravis[J].J Neurol Sci,2012,313(1-2):27-31.
[25]Shiao YM,Lee CC,Hsu YH,et al.Ectopic and high CX-CL13chemokine expression in myasthenia gravis with thymiclymphoid hyperplasia[J].J Neuroimmunol,2010,221(1-2):101-106.
[26]Kaminski HJ,Kusner LL,Richmonds C,et al.Deficiency ofdecay accelerating factor and CD59leads to crisis in experi-mental myasthenia[J].Exp Neurol,2006,202(2):287-293.
[27]Tüzün E,Scott BG,Goluszko E,et al.Genetic evidence forinvolvement of classical complement pathway in induction ofexperimental autoimmune myasthenia gravis[J].J Immunol,2003,171(7):3847-3854.