Corrigenda

Vandenbark, Arthur A.; Chou, Yuan K.; Mass, R.; Buenafe, Abigail C.; Liefeld, Diane; Kavanagh, Daniel G.; Cooper, Shelley; Hashim, George A.; Offner, Halina; Bourdette, Dennis

doi:10.1038/nm0297-240

Cited by 3 publications

(3 citation statements)

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“…In pilot clinical trials of TCR peptide vaccination, MS patients were immunized with synthetic peptides derived from the CDR regions of different V␤5 and V␤6 elements (132)(133)(134)(135)(136) (138,139).…”

Section: Ga (Copolymer 1 Copaxone)mentioning

confidence: 99%

Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines

Hohlfeld

Wekerle

2004

Proc. Natl. Acad. Sci. U.S.A.

223

133

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Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of multiple sclerosis (MS), and thus are logical targets for therapy. Indeed, several immunomodulatory agents, including IFN-␤1b, IFN-␤1a, glatiramer acetate, and mitoxantrone, have had beneficial clinical effects in different forms of MS. However, because the available treatments are only partially effective, MS therapy needs to be further improved. Selective (antigen-specific) immunotherapies are especially appealing because in theory they combine maximal efficacy with minimal side effects. Indeed, several innovative immunotherapies have been successfully applied in experimental autoimmune encephalomyelitis. For example, autoreactive T cells can be selectively targeted by means of antigen, T cell receptor, or activation markers. However, experimental autoimmune encephalomyelitis is far from being a perfect approximation of MS because MS is more heterogeneous and the target antigen(s) is (are) not known. Further advances in MS therapy will depend on our growing understanding of the pathogenesis of this still incurable disease.

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Section: Ga (Copolymer 1 Copaxone)mentioning

confidence: 99%

Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines

Hohlfeld

Wekerle

2004

Proc. Natl. Acad. Sci. U.S.A.

223

133

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“…The importance of the DRB1*1501-associated MBP 85-99 epitope in the pathogenesis of MS has been particularly proposed based on data that, in MS lesions, the microglia͞ macrophages were positive for the HLA-DR2͞MBP 85-99 complex detected by a monoclonal antibody specific for this complex (13). Moreover, mice transgenic (tg) for HLA-DR2 and the TCR from an MS patient develop EAE spontaneously in 6-12 months and the disease appearance can be accelerated by immunization with MBP 85-99 (14).Several clinical attempts have been made to interfere with the MHC II͞MBP 85-99͞TCR trimolecular complex with varying effectiveness (8,(15)(16)(17)(18)(19). Currently, Copolymer 1 (Cop1, Copaxone, glatiramer acetate) is used in MS patients as an immunomodulator (20)(21)(22).…”

mentioning

confidence: 99%

“…Several clinical attempts have been made to interfere with the MHC II͞MBP 85-99͞TCR trimolecular complex with varying effectiveness (8,(15)(16)(17)(18)(19). Currently, Copolymer 1 (Cop1, Copaxone, glatiramer acetate) is used in MS patients as an immunomodulator (20)(21)(22).…”

mentioning

confidence: 99%

Modified amino acid copolymers suppress myelin basic protein 85–99-induced encephalomyelitis in humanized mice through different effects on T cells

Illés

Stern

Reddy

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Human HLA-DR2, and specifically that encoded by the DRA͞DRB1*1501 alleles, is thought to be important in the presentation of the immunodominant epitope MBP 85-99 (9, 10). Although the association of the human MHC class II (MHC II) locus with MS has consistently been observed in genome-wide scans (11), an association of the HLA-DR2, DQ6 haplotype, including the DRB1*1501 allele, with susceptibility to MS has been suggested in several population-and family-based studies (12). The importance of the DRB1*1501-associated MBP 85-99 epitope in the pathogenesis of MS has been particularly proposed based on data that, in MS lesions, the microglia͞ macrophages were positive for the HLA-DR2͞MBP 85-99 complex detected by a monoclonal antibody specific for this complex (13). Moreover, mice transgenic (tg) for HLA-DR2 and the TCR from an MS patient develop EAE spontaneously in 6-12 months and the disease appearance can be accelerated by immunization with MBP 85-99 (14).Several clinical attempts have been made to interfere with the MHC II͞MBP 85-99͞TCR trimolecular complex with varying effectiveness (8,(15)(16)(17)(18)(19). Currently, Copolymer 1 (Cop1, Copaxone, glatiramer acetate) is used in MS patients as an immunomodulator (20)(21)(22). Cop1 is a random polypeptide synthesized from four amino acids, L-tyrosine, L-glutamic acid, L-alanine, and L-lysine [poly(Y,E,A,K)n], in a specific molar ratio of 1.0, 1.4, 4.2, and 3.4, respectively. Although the mechanism of action of Cop1 is not fully understood, several immunologic effects have been suggested (23,24). These include competition of Cop1 with the immunodominant MBP 85-99 peptide for binding to DRB1*1501 and competition of MHC II͞Cop1 and MHC II͞MBP complexes for binding to the TCR (23,(25)(26)(27)(28). Cop1 has also recently been shown to polarize T cells into a T helper 2 (Th2) phenotype. Splenocytes from Cop1-immunized mice transfer protection against EAE, and Cop1-specific Th2 cells capable of secreting IL-4 and IL-10 dominate in the CNS of protected mice (29). Similarly, MS patients treated with Cop1 have Cop1-specific T cells with a Th2 phenotype (30).Although widely used in the treatment of MS, Cop1 reduces the frequency of relapses by only Ϸ30% (21). We hypothesized that by improving the binding capacity of copolymers to HLA-DR2 relative to MBP 85-99, it may be possible to develop a more effective immunomodulator. Several random 4-aa copolymers were designed based on the knowledge of anchor residues used by the immunodominant MBP 85-99 epitope that bind to the DRB1*1501-encoded molecule. To determine the in vivo and in vitro effect of these copolymers, a humanized double-tg mouse

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17β-Estradiol Attenuates Neural Cell Apoptosis Through Inhibition of JNK Phosphorylation in SCI Rats and Excitotoxicity Induced by Glutamate In Vitro

Rong¹,

Wang²,

Liu³

et al. 2012

International Journal of Neuroscience

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We investigated whether 17β-estradiol (E2) treatment could prevent the apoptosis of neural cells after spinal cord injury (SCI) and cultured cortical cells through inhibition of JNK (c-Jun N-terminal kinase) phosphorylation. SCI-induced rats were randomly divided into three groups: control, E2-treated, and sham-treated. Five rats from each group were sacrificed at 2, 4, 6, 12, or 24 h postinjury. Apoptotic neural cells were assessed using the TUNEL method. JNK phosphorylation was detected with immunohistochemistry. Cultured cortical cells were pretreated with E2 and the specific JNK inhibitor SP600125 and then treated with glutamate-induced cytotoxicity in vitro. Neuron viability was determined with an methyl thiazolyl tetrazolium (MTT) assay, morphology of apoptotic cells was observed with 4',6-diamidino-2-phenylindole (DAPI) staining, and JNK phosphorylation was detected using Western blot analysis. Treatment with E2 reduced neuron apoptosis and inhibited JNK phosphorylation. Moreover, the number of apoptotic cells was correlated with JNK phosphorylation 24 h after the rats suffered the SCI. Pretreatment with E2 significantly maintained neural cell viability, attenuated apoptosis, and inhibited JNK phosphorylation induced by glutamate in vitro. These neuroprotective effects of E2 on neural cells were blocked by the co-administration of SP600125. Our results suggest that neuroprotection from E2 is partially mediated by the inhibition of JNK phosphorylation.

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Corrigenda

Cited by 3 publications

References 0 publications

Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines

Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines

Modified amino acid copolymers suppress myelin basic protein 85–99-induced encephalomyelitis in humanized mice through different effects on T cells

17β-Estradiol Attenuates Neural Cell Apoptosis Through Inhibition of JNK Phosphorylation in SCI Rats and Excitotoxicity Induced by Glutamate In Vitro

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