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December 10, 1997, Vol 278, No. 22 >
ARTICLE | December 10, 1997

Immunologic Aspects of Neurologic and Neuromuscular Diseases FREE

Derek R. Smith, MD; Howard L. Weiner, MD
JAMA. 1997;278(22):1956-1961. doi:10.1001/jama.1997.03550220162021
Text Size: A A A
Published online
Article
References

Inflammatory disorders of the nervous and neuromuscular system are not uncommon despite the fact that immune privilege exists in much of the nervous system. Common immune-mediated neurologic diseases include multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic polymyositis. Environmental, genetic, and immunologic factors have been postulated to be involved in the pathogenesis of these diseases, but much remains to be elucidated about the specific identity and relative contributions of these factors. Several new therapies have become available for these diseases in the past few years, and many others are under investigation. Strategies that enhance the normal tolerance mechanisms of the immune system are being developed. In particular, strategies to block TH1-type responses or enhance TH2/3-type responses have generated interest.

REFERENCES

1 +
French L, Hahne M, Viard I, et al.  Fas and Fas ligand in embryos and adult mice: ligand expression in several immune privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover . J Cell Biol . 1996;;133:335-343.
2 +
Steinman L, Lindsey JW, Alters S, Hodgkinson S.  From treatment of experimental allergic encephalomyelitis to clinical trials in multiple sclerosis . In: Bach JF, ed. Monoclonal Antibodies and Peptide Therapy in Autoimmune Diseases . New York, NY: Marcel Dekker Inc; 1993;:253-260.
3 +
Ben-Nun A, Wekerle H, Cohen IR.  Vaccination against autoimmune encephalomyelitis using attenuated cells of a T lymphocyte line reactive against myelin basic protein . Nature . 1981;;292:60-61.
4 +
Khoury SJ, Hancock WW, Weiner HL.  Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with down-regulation of inflammatory cytokines and differential upregulation of TGFb, IL-4 and PGE expression in the brain . J Exp Med . 1992;;46:1355-1364.
5 +
Chen Y, Kuchroo VK, Inobe J-I, Hafler DA, Weiner HL.  Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis . Science . 1994;;265:1237-1240.
6 +
Engel A, Emslie-Smith A.  Inflammatory myopathies . Curr Opin Neurol Neurosurg . 1989;;2:695.
7 +
Kissel J, Mendell J, Rammohan K.  Microvascular deposition of complement membrane attack complex in dermatomyositis . N Engl J Med . 1986;;314:329-334.
8 +
Hohlfield R, Engel A, Kunio L, Harper R.  Polymyositis mediated by T lymphocytes that express gamma/delta receptors . N Engl J Med . 1991;;324:877-881.
9 +
Kalovidouris A, Pourmand R, Passo M, Plotkin Z.  Proliferative response of PBMC to autologous and allogenic muscle in patients with PM/DM . Arthritis Rheum . 1989;;32:446-443.
10 +
Targoff I.  Immune manifestations of inflammatory muscle disease . Rheum Dis Clin North Am . 1994;;20:857-880.
11 +
Miller F, Leitman S, Cronin M, et al.  Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis . N Engl J Med . 1992;;326:1380-1384.
12 +
Truffault F, Cohen-Kaminsky S, Khalil I, Levasseur P, Berrih-Aknin S.  Altered intrathymic T cell repertoire in human myasthenia gravis . Ann Neurol . 1997;;41:731-741.
13 +
Yi Q, Lefvert A.  Idiotype and anti-idiotype reactive T lymphocytes in myasthenia gravis: evidence for the involvement of different subpopulations of T helper lymphocytes . J Immunol . 1994;;153:3353-3359.
14 +
Durelli I, Maggi G, Casadio C, et al.  Actuarial analysis of the occurrence of remission following thymectomy for myasthenia gravis in 400 patients . J Neurol Neurosurg Psychol . 1991;;54:406.
15 +
Sela M, Kirshner S, Katz-Levy Y, et al.  Dominant epitopes and synthetic peptides in myasthenia gravis . Israel J Med Sci . 1995;;31:10.
16 +
Wang Z, Huang J, Olsson T, He B, Link H.  B cell responses to AChR in rats orally tolerized against EAMG . J Neurol Sci . 1995;;128:167-174.
17 +
Latov N.  Evaluation and treatment of patients with neuropathy and monoclonal gammopathy . Semin Neurol . 1994;;14:118-122.
18 +
Notermans NC, Lokhorst HM, Franssen II, et al.  Intermittent cyclophosphamide and prednisone treatment of polyneuropathy associated with monoclonal gammopathy of undetermined significance . Neurology . 1996;;47:1227-1233.
19 +
Pestronk A, Lopate G, Kornberg AJ, et al.  Distal lower motor neuron syndrome with high-titer serum IgM anti-GM1 antibodies' improvement following immunotherapy with monthly plasma exchange and intravenous cyclophosphamide . Neurology . 1994;;44:2027-2031.
20 +
Ibsen S, Clausen J.  A repetitive DNA sequence 5' to the human myelin basic protein gene may be linked to MS in Danes . Acta Neurologica Scandinavica . 1996;;93:236-240.
21 +
Windhagen A, Newcombe J, Dangond F, et al.  Expression of costimulatory molecules B7-1, B7-2, and IL-12 in MS lesions . J Exp Med . 1995;;182:1985-1996.
22 +
Gerritse K, Laman J, Noelle R, et al.  CD40-CD40L interactions in EAE and MS . Proc Natl Acad Sci U S A . 1996;;93:2499-2504.
23 +
Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner H, Hafler D.  Increased frequency of IL-2 responsive T cells specific for MBP and PLP in peripheral blood and CSF of patients with MS . J Exp Med . 1994;;179:973-984.
24 +
Lodge P, Johnson C, Sriram S.  Frequency of MBP and MBP peptide reactive T cells in the HPRT mutant T cell population of MS patients . Neurology . 1996;;46:1410-1415.
25 +
Kerero de Rosbo N, Milo R, Lees M, Burger D, Bernard C, Ben-Nun A.  Reactivity to myelin antigens in MS: PBL respond predominantly to MOG . J Clin Invest . 1993;;92:2602-2608.
26 +
Balashov K, Smith D, Hafler D, Khoury S, Weiner H.  Increased IL-12 production in progressive MS: induction by activated CD4 T cells via CD40 ligand . Proc Natl Acad Sci U S A . 1997;;94:599-603.
27 +
Haines J, Ter-Minassian M, Bazyk A, et al.  A complete genomic screen for multiple sclerosis underscores a role for the major histocompatibility complex: the Multiple Sclerosis Genetics Group . Nat Genet . 1996;;13:469-471.
28 +
Paty DW, Li DKB, and IFN-B MS Study Group.  Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: MRI results of amulticenter, randomized, double-blind, placebo-controlled trial . Neurology . 1993;;43:662-667.
29 +
Kupersmith MJ, Kaufman D, Paty DW, et al.  Megadose corticosteroids in multiple sclerosis . Neurology . 1994;;44:1-4.
30 +
Beck RW, Cleary PA, Anderson MM Jr, et al.  A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis . N Engl J Med . 1992;;326:581-588.
31 +
Beck RW, Cleary PA, Trobe JD, et al.  The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis . N Engl J Med . 1993;;239:1764-1769.
32 +
Group TIMSS.  Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: clinical results of a multicenter, randomized, double-blind, placebo-controlled trial . Neurology . 1993;;43:655-661.
33 +
IFN-B MS Study Group.  Interferon beta-lb in the treatment of multiple sclerosis: final outcome of the randomized controlled trial . Neurology . 1995;;45:1277.
34 +
Jacobs L.  Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis . Ann Neurol . 1996;;39:285-294.
35 +
Durelli L, Bongioanni M, Ferrero B, et al.  Interferon alpha treatment of relapsing remitting multiple sclerosis: disease activity resumes after stopping treatment . Neurology . 1996;;47:123-129.
36 +
David M, Petricoin EI, Benjamin C, et al.  Requirement of MAP kinase (ERK2) activity in interferon alpha and interferon beta stimulated gene expression through STAT proteins . Science . 1995;;269:1721.
37 +
Arnason BGW.  Interferon beta in multiple sclerosis . Neurology . 1993;;43:641-643.
38 +
Hirsch RL, Panitch HS, Johnson KP.  Lymphocytes from multiple sclerosis patients produce elevated levels of gamma interferon in vitro . J Clin Invest . 1987;;22:139.
39 +
Noronha A, Toscas A, Jensen MA.  IFN-b downregulates T cell activation and IFN-g production: implications for MS . JNeuroimmunol . 1993;;46:145.
40 +
Smith D, Balshov K, Hafler D, Khoury S, Weiner H.  Immune deviation following cyclophosphamide/ methylprednisolone treatment of multiple sclerosis: increased IL-4 and associated eosinophilia . Ann Neurol . 1997;;42:313-318.
41 +
Rudick R.  In vitro and in vivo inhibition of mitogen driven T cell activation by recombinant interferon beta . Neurology . 1993;;43:2080-2087.
42 +
Porrini AM, Gambi D, Reder AT.  Interferon effects on IL-10 secretion: mononuclear cell response to IL-10 is normal in multiple sclerosis patients . J Neuroimmunol . 1995;;61:27-34.
43 +
Johnson K, Brooks B, Cohen J, et al.  Copolymer 1 reduces relapse rate and improves disability in relapsing remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial . Neurology . 1995;;45:1268.
44 +
Weiner HL, Mackin GA, Matsui M, et al.  Doubleblind pilot trial of oral tolerization with myelin antigens in multiple sclerosis . Science . 1993;;259:1321-1324.
45 +
Weiner HL, Mackin GA, Orav EJ, et al.  Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group . Neurology . 1993;;43:910-918.
46 +
Edan G, Miller D, Clanet M, et al.  Therapeutic effect of mitoxantrone combined with methylprednisolone in MS: a randomized multicentre study of active disease using MRI and clinical criteria . J Neurol Neurosurg Psychol . 1997;;62:112-118.
47 +
Goodkin D, Rudick R, Vander Brug Medendorp S, et al.  Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis . Ann Neurol . 1995;;37:30.
48 +
Sipe JD, Romine J, Koziol J, McMillan R, Zyroff J, Beutler E.  Cladribine in the treatment of chronic progressive multiple sclerosis . Lancet . 1994;;344:9.
49 +
Furneaux H, Reich L, Posner J.  Autoantibody synthesis in the CNS of patients with paraneoplastic syndromes . Neurology . 1990;;7:1085-1091.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
French L, Hahne M, Viard I, et al.  Fas and Fas ligand in embryos and adult mice: ligand expression in several immune privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover . J Cell Biol . 1996;;133:335-343.
2 +
Steinman L, Lindsey JW, Alters S, Hodgkinson S.  From treatment of experimental allergic encephalomyelitis to clinical trials in multiple sclerosis . In: Bach JF, ed. Monoclonal Antibodies and Peptide Therapy in Autoimmune Diseases . New York, NY: Marcel Dekker Inc; 1993;:253-260.
3 +
Ben-Nun A, Wekerle H, Cohen IR.  Vaccination against autoimmune encephalomyelitis using attenuated cells of a T lymphocyte line reactive against myelin basic protein . Nature . 1981;;292:60-61.
4 +
Khoury SJ, Hancock WW, Weiner HL.  Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with down-regulation of inflammatory cytokines and differential upregulation of TGFb, IL-4 and PGE expression in the brain . J Exp Med . 1992;;46:1355-1364.
5 +
Chen Y, Kuchroo VK, Inobe J-I, Hafler DA, Weiner HL.  Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis . Science . 1994;;265:1237-1240.
6 +
Engel A, Emslie-Smith A.  Inflammatory myopathies . Curr Opin Neurol Neurosurg . 1989;;2:695.
7 +
Kissel J, Mendell J, Rammohan K.  Microvascular deposition of complement membrane attack complex in dermatomyositis . N Engl J Med . 1986;;314:329-334.
8 +
Hohlfield R, Engel A, Kunio L, Harper R.  Polymyositis mediated by T lymphocytes that express gamma/delta receptors . N Engl J Med . 1991;;324:877-881.
9 +
Kalovidouris A, Pourmand R, Passo M, Plotkin Z.  Proliferative response of PBMC to autologous and allogenic muscle in patients with PM/DM . Arthritis Rheum . 1989;;32:446-443.
10 +
Targoff I.  Immune manifestations of inflammatory muscle disease . Rheum Dis Clin North Am . 1994;;20:857-880.
11 +
Miller F, Leitman S, Cronin M, et al.  Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis . N Engl J Med . 1992;;326:1380-1384.
12 +
Truffault F, Cohen-Kaminsky S, Khalil I, Levasseur P, Berrih-Aknin S.  Altered intrathymic T cell repertoire in human myasthenia gravis . Ann Neurol . 1997;;41:731-741.
13 +
Yi Q, Lefvert A.  Idiotype and anti-idiotype reactive T lymphocytes in myasthenia gravis: evidence for the involvement of different subpopulations of T helper lymphocytes . J Immunol . 1994;;153:3353-3359.
14 +
Durelli I, Maggi G, Casadio C, et al.  Actuarial analysis of the occurrence of remission following thymectomy for myasthenia gravis in 400 patients . J Neurol Neurosurg Psychol . 1991;;54:406.
15 +
Sela M, Kirshner S, Katz-Levy Y, et al.  Dominant epitopes and synthetic peptides in myasthenia gravis . Israel J Med Sci . 1995;;31:10.
16 +
Wang Z, Huang J, Olsson T, He B, Link H.  B cell responses to AChR in rats orally tolerized against EAMG . J Neurol Sci . 1995;;128:167-174.
17 +
Latov N.  Evaluation and treatment of patients with neuropathy and monoclonal gammopathy . Semin Neurol . 1994;;14:118-122.
18 +
Notermans NC, Lokhorst HM, Franssen II, et al.  Intermittent cyclophosphamide and prednisone treatment of polyneuropathy associated with monoclonal gammopathy of undetermined significance . Neurology . 1996;;47:1227-1233.
19 +
Pestronk A, Lopate G, Kornberg AJ, et al.  Distal lower motor neuron syndrome with high-titer serum IgM anti-GM1 antibodies' improvement following immunotherapy with monthly plasma exchange and intravenous cyclophosphamide . Neurology . 1994;;44:2027-2031.
20 +
Ibsen S, Clausen J.  A repetitive DNA sequence 5' to the human myelin basic protein gene may be linked to MS in Danes . Acta Neurologica Scandinavica . 1996;;93:236-240.
21 +
Windhagen A, Newcombe J, Dangond F, et al.  Expression of costimulatory molecules B7-1, B7-2, and IL-12 in MS lesions . J Exp Med . 1995;;182:1985-1996.
22 +
Gerritse K, Laman J, Noelle R, et al.  CD40-CD40L interactions in EAE and MS . Proc Natl Acad Sci U S A . 1996;;93:2499-2504.
23 +
Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner H, Hafler D.  Increased frequency of IL-2 responsive T cells specific for MBP and PLP in peripheral blood and CSF of patients with MS . J Exp Med . 1994;;179:973-984.
24 +
Lodge P, Johnson C, Sriram S.  Frequency of MBP and MBP peptide reactive T cells in the HPRT mutant T cell population of MS patients . Neurology . 1996;;46:1410-1415.
25 +
Kerero de Rosbo N, Milo R, Lees M, Burger D, Bernard C, Ben-Nun A.  Reactivity to myelin antigens in MS: PBL respond predominantly to MOG . J Clin Invest . 1993;;92:2602-2608.
26 +
Balashov K, Smith D, Hafler D, Khoury S, Weiner H.  Increased IL-12 production in progressive MS: induction by activated CD4 T cells via CD40 ligand . Proc Natl Acad Sci U S A . 1997;;94:599-603.
27 +
Haines J, Ter-Minassian M, Bazyk A, et al.  A complete genomic screen for multiple sclerosis underscores a role for the major histocompatibility complex: the Multiple Sclerosis Genetics Group . Nat Genet . 1996;;13:469-471.
28 +
Paty DW, Li DKB, and IFN-B MS Study Group.  Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: MRI results of amulticenter, randomized, double-blind, placebo-controlled trial . Neurology . 1993;;43:662-667.
29 +
Kupersmith MJ, Kaufman D, Paty DW, et al.  Megadose corticosteroids in multiple sclerosis . Neurology . 1994;;44:1-4.
30 +
Beck RW, Cleary PA, Anderson MM Jr, et al.  A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis . N Engl J Med . 1992;;326:581-588.
31 +
Beck RW, Cleary PA, Trobe JD, et al.  The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis . N Engl J Med . 1993;;239:1764-1769.
32 +
Group TIMSS.  Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: clinical results of a multicenter, randomized, double-blind, placebo-controlled trial . Neurology . 1993;;43:655-661.
33 +
IFN-B MS Study Group.  Interferon beta-lb in the treatment of multiple sclerosis: final outcome of the randomized controlled trial . Neurology . 1995;;45:1277.
34 +
Jacobs L.  Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis . Ann Neurol . 1996;;39:285-294.
35 +
Durelli L, Bongioanni M, Ferrero B, et al.  Interferon alpha treatment of relapsing remitting multiple sclerosis: disease activity resumes after stopping treatment . Neurology . 1996;;47:123-129.
36 +
David M, Petricoin EI, Benjamin C, et al.  Requirement of MAP kinase (ERK2) activity in interferon alpha and interferon beta stimulated gene expression through STAT proteins . Science . 1995;;269:1721.
37 +
Arnason BGW.  Interferon beta in multiple sclerosis . Neurology . 1993;;43:641-643.
38 +
Hirsch RL, Panitch HS, Johnson KP.  Lymphocytes from multiple sclerosis patients produce elevated levels of gamma interferon in vitro . J Clin Invest . 1987;;22:139.
39 +
Noronha A, Toscas A, Jensen MA.  IFN-b downregulates T cell activation and IFN-g production: implications for MS . JNeuroimmunol . 1993;;46:145.
40 +
Smith D, Balshov K, Hafler D, Khoury S, Weiner H.  Immune deviation following cyclophosphamide/ methylprednisolone treatment of multiple sclerosis: increased IL-4 and associated eosinophilia . Ann Neurol . 1997;;42:313-318.
41 +
Rudick R.  In vitro and in vivo inhibition of mitogen driven T cell activation by recombinant interferon beta . Neurology . 1993;;43:2080-2087.
42 +
Porrini AM, Gambi D, Reder AT.  Interferon effects on IL-10 secretion: mononuclear cell response to IL-10 is normal in multiple sclerosis patients . J Neuroimmunol . 1995;;61:27-34.
43 +
Johnson K, Brooks B, Cohen J, et al.  Copolymer 1 reduces relapse rate and improves disability in relapsing remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial . Neurology . 1995;;45:1268.
44 +
Weiner HL, Mackin GA, Matsui M, et al.  Doubleblind pilot trial of oral tolerization with myelin antigens in multiple sclerosis . Science . 1993;;259:1321-1324.
45 +
Weiner HL, Mackin GA, Orav EJ, et al.  Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group . Neurology . 1993;;43:910-918.
46 +
Edan G, Miller D, Clanet M, et al.  Therapeutic effect of mitoxantrone combined with methylprednisolone in MS: a randomized multicentre study of active disease using MRI and clinical criteria . J Neurol Neurosurg Psychol . 1997;;62:112-118.
47 +
Goodkin D, Rudick R, Vander Brug Medendorp S, et al.  Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis . Ann Neurol . 1995;;37:30.
48 +
Sipe JD, Romine J, Koziol J, McMillan R, Zyroff J, Beutler E.  Cladribine in the treatment of chronic progressive multiple sclerosis . Lancet . 1994;;344:9.
49 +
Furneaux H, Reich L, Posner J.  Autoantibody synthesis in the CNS of patients with paraneoplastic syndromes . Neurology . 1990;;7:1085-1091.

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