Kappos, L. et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group. Nat. Med. 6, 1176-1182
In this ‘double-blind’, randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing–remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.
[Show abstract][Hide abstract] ABSTRACT: Two clinical trials testing an altered peptide ligand (APL) in multiple sclerosis report seemingly contradictory results. Immunologic analysis shows that the biological effects of APLs extend far beyond what was initially envisioned, raising important issues for the development of this type of therapy (pages 1167-1175 and 1176-1182).
Nature Medicine 11/2000; 6(10):1098-100. DOI:10.1038/80424 · 27.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: T cell recognition of autoantigens is critical to progressive immune-mediated destruction of islet cells, which leads to autoimmune diabetes. We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. T cell responses were antagonized by altered peptide ligands containing single amino acid modifications. This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM.
Proceedings of the National Academy of Sciences 03/2001; 98(4):1763-8. DOI:10.1073/pnas.98.4.1763 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The triggering of autoimmunity by infection or immunization is often blamed on antigenic mimicry. But the concept of antigen mimicry impinges on our understanding of adaptive immunity in general, and not only on autoimmunity. Here are some thoughts about the consequences of immune mimicry.
Journal of Autoimmunity 06/2001; 16(3):337-40. DOI:10.1006/jaut.2000.0481 · 8.41 Impact Factor
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