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Science 26 February 1993:
Vol. 259. no. 5099, pp. 1321 - 1324
DOI: 10.1126/science.7680493
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Articles

Science, Vol 259, Issue 5099, 1321-1324
Copyright © 1993 by American Association for the Advancement of Science

articles

Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis

HL Weiner, GA Mackin, M Matsui, EJ Orav, SJ Khoury, DM Dawson, and DA Hafler

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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CD8+ T Cell-Mediated HLA-A*0201-Restricted Cytotoxicity to Transaldolase Peptide 168-176 in Patients with Multiple Sclerosis.
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J. Immunol. 175, 8365-8378
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Differential induction of IgE-mediated anaphylaxis after soluble vs. cell-bound tolerogenic peptide therapy of autoimmune encephalomyelitis.
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Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines.
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Pancreatic {beta}-Cell Function and Immune Responses to Insulin After Administration of Intranasal Insulin to Humans At Risk for Type 1 Diabetes.
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CCR5 Regulates High Dose Oral Tolerance by Modulating CC Chemokine Ligand 2 Levels in the GALT.
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J. Immunol. 173, 314-320
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Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis.
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Autoimmune Diseases.
A. Davidson and B. Diamond (2001)
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L. Cohn (2001)
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Vaccination Strategies for Mucosal Immune Responses.
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T. Kamradt and N. A. Mitchison (2001)
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Regulation of Encephalitogenic T Cells with Recombinant TCR Ligands.
G. G. Burrows, K. L. Adlard, B. F. Bebo Jr., J. W. Chang, K. Tenditnyy, A. A. Vandenbark, and H. Offner (2000)
J. Immunol. 164, 6366-6371
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Effect of Multiple Antigenic Exposures in the Gut on Oral Tolerance and Induction of Antibacterial Systemic Immunity.
S. Garg, V. Bal, S. Rath, and A. George (1999)
Infect. Immun. 67, 5917-5924
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Adenoviral Gene Therapy With Catalase Suppresses Experimental Optic Neuritis.
J. Guy, X. Qi, H. Wang, and W. W. Hauswirth (1999)
Arch Ophthalmol 117, 1533-1539
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Kinetic Analysis of Oral Tolerance: Memory Lymphocytes Are Refractory to Oral Tolerance.
Y. Chung, S.-Y. Chang, and C.-Y. Kang (1999)
J. Immunol. 163, 3692-3698
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Suppression of induction of experimental immune mediated blepharoconjunctivitis by tolerogenic conjugates of the antigen and monomethoxypolyethylene glycol.
A. Fukushima, K. Nishino, H. Yoshida, M. Takata, and H. Ueno (1999)
Br. J. Ophthalmol. 83, 973-979
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Candidate autoantigens in multiple sclerosis.
S. Schmidt (1999)
Multiple Sclerosis 5, 147-160
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Antigen-Specific T Cell Activation and Proliferation During Oral Tolerance Induction.
J. Sun, B. Dirden-Kramer, K. Ito, P. B. Ernst, and N. Van Houten (1999)
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Oral Administration of Myelin Basic Protein Is Superior to Myelin in Suppressing Established Relapsing Experimental Autoimmune Encephalomyelitis.
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Immunomodulation of experimental autoimmune encephalomyelitis by oral administration of copolymer 1.
D. Teitelbaum, R. Arnon, and M. Sela (1999)
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Oral tolerance in disease.
P GARSIDE, A M. MOWAT, and A KHORUTS (1999)
Gut 44, 137-142
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Two-Domain MHC Class II Molecules Form Stable Complexes with Myelin Basic Protein 69-89 Peptide That Detect and Inhibit Rat Encephalitogenic T Cells and Treat Experimental Autoimmune Encephalomyelitis.
G. G. Burrows, B. F. Bebo Jr., K. L. Adlard, A. A. Vandenbark, and H. Offner (1998)
J. Immunol. 161, 5987-5996
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Oral Tolerance to Low Dose {beta}2-Glycoprotein I: Immunomodulation of Experimental Antiphospholipid Syndrome.
M. Blank, J. George, V. Barak, A. Tincani, T. Koike, and Y. Shoenfeld (1998)
J. Immunol. 161, 5303-5312
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Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis.
J. Guy, X. Qi, and W. W. Hauswirth (1998)
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Induction of Oral Tolerance in TGF-{beta}1 Null Mice.
K. S. Barone, D. D. Tolarova, I. Ormsby, T. Doetschman, and J. G. Michael (1998)
J. Immunol. 161, 154-160
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HLA-G Isoforms Produced by Placental Cytotrophoblasts and Found in Amniotic Fluid Are Due to Unusual Glycosylation.
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J. Immunol. 160, 5922-5928
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Myelin reactive T cells in the autoimmune pathogenesis of multiple sclerosis.
P. Stinissen, R. Medaer, and J. Raus (1998)
Multiple Sclerosis 4, 203-211
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Myelin basic protein-like material in the urine of multiple sclerosis patients: relationships to clinical and neuroimaging changes.
J. N Whitaker (1998)
Multiple Sclerosis 4, 243-246
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Immunologic Aspects of Neurologic and Neuromuscular Diseases.
D. R. Smith and H. L. Weiner (1997)
JAMA 278, 1956-1961
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Gut Response: Therapy With Ingested Immunomodulatory Proteins.
S. A. Brod (1997)
Arch Neurol 54, 1300-1302
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Oral administration of antigen in the treatment of eye disease.
K A WILLIAMS (1997)
Br. J. Ophthalmol. 81, 714-715
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Oral immunisation as a strategy for enhancing corneal allograft survival.
D. Ma, J. Mellon, and J. Y Niederkorn (1997)
Br. J. Ophthalmol. 81, 778-784
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A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes.
I. Bergerot, C. Ploix, J. Petersen, V. Moulin, C. Rask, N. Fabien, M. Lindblad, A. Mayer, C. Czerkinsky, J. Holmgren, et al. (1997)
PNAS 94, 4610-4614
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Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis.
B. J. Prakken, R. van der Zee, S. M. Anderton, P. J. S. van Kooten, W. Kuis, and W. van Eden (1997)
PNAS 94, 3284-3289
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Immunologic Mechanisms of Uveitis: New Targets for Immunomodulation.
S. M. Whitcup and R. B. Nussenblatt (1997)
Arch Ophthalmol 115, 520-525
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Interphotoreceptor retinoid binding protein is a potent tolerogen in Lewis rat: suppression of experimental autoimmune uveoretinitis is retinal antigen specific.
B. Laliotou, J. Liversidge, J. V Forrester, and A. D Dick (1997)
Br. J. Ophthalmol. 81, 61-67
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Multiple Sclerosis: New Approaches to Immunotherapy.
T. L. Vollmer (1996)
Neuroscientist 2, 127-136
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Measuring Patient-Centered Outcomes in Neurologic Disease: Extending the Q-TWiST Method.
C. E. Schwartz, B. F. Cole, and R. D. Gelber (1995)
Arch Neurol 52, 754-762
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T-Helper 1-Type Immunity to Trophoblast in Women With Recurrent Spontaneous Abortion.
J. A. Hill, K. Polgar, and D. J. Anderson (1995)
JAMA 273, 1933-1936
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Allergy and Immunology.
C. Cunningham-Rundles (1995)
JAMA 273, 1659-1660
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The Pathogenesis of Insulin-Dependent Diabetes Mellitus.
M. A. Atkinson and N. K. Maclaren (1994)
N. Engl. J. Med. 331, 1428-1436
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Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis.
Y Chen, V. Kuchroo, J Inobe, D. Hafler, and H. Weiner (1994)
Science 265, 1237-1240
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Genetic Factors in Multiple Sclerosis.
J. R. Oksenberg, A. B. Begovich, H. A. Erlich, and L. Steinman (1993)
JAMA 270, 2362-2369
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Effects of oral administration of type II collagen on rheumatoid arthritis.
D. Trentham, R. Dynesius-Trentham, E. Orav, D Combitchi, C Lorenzo, K. Sewell, D. Hafler, and H. Weiner (1993)
Science 261, 1727-1730
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A NOVEL TREATMENT FOR MULTIPLE SCLEROSIS.
(1993)
Journal Watch (General) 1993, 5
   Full Text »
Design, Engineering, and Production of Human Recombinant T Cell Receptor Ligands Derived from Human Leukocyte Antigen DR2.
J. W. Chang, D. E. Mechling, H.-P. Bachinger, and G. G. Burrows (2001)
J. Biol. Chem. 276, 24170-24176
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Specific treatment of autoimmunity with recombinant invariant chains in which CLIP is replaced by self-epitopes.
F. Bischof, W. Wienhold, C. Wirblich, G. Malcherek, O. Zevering, A. M. Kruisbeek, and A. Melms (2001)
PNAS 98, 12168-12173
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