NBI-5788, an altered MBP83-99 peptide, induces a T-helper 2-like immune response in multiple sclerosis patients.

Abstract

We assessed the immune response induced in multiple sclerosis (MS) patients who had received NBI-5788, an altered peptide ligand (APL) designed from an immunodominant region (83-99) of the neuroantigen myelin basic protein (MBP) (5, 10, or 20 mg subcutaneously weekly for 4 weeks). The mean frequency of NBI-5788-responsive T cells (stimulation index > 3) in MS patients treated with the APL was 35.8 +/- 12.8% (n = 7) compared with a mean frequency of 6.2 +/- 1.3% (n = 7) for the untreated patients. The mean frequency of whole MBP-responsive T cells in MS patients treated with the APL was not significantly different from that of untreated patients (16.4 +/- 5.7% vs 18.0 +/- 6.3%, respectively). NBI-5788-reactive T-cell lines generated from NBI-5788-treated patients exhibited an increased frequency of cross-reactivity with MBP peptide 83-99 compared with NBI-5788-reactive lines from control MS patients. Cytokine secretion by APL-reactive T-cell lines from NBI-5788-treated MS patients was more frequently T-helper 2-like compared with T-cell lines from untreated MS patients. These results demonstrate that subcutaneous administration of a soluble APL based on the MBP peptide 83-99 in MS patients can induce an APL-reactive immune response in which T lymphocytes cross-reactive with the immunodominant neuroantigen MBP secrete anti-inflammatory cytokines. The significant heterogeneity in immune response between individuals indicates the need for clinical laboratory correlation during the course of therapeutic trials.

• Authors: P D Crowe, Y Qin, P J Conlon, J P Antel
• Journal: Annals of neurology (Ann Neurol) Vol. 48 Issue 5 Pg. 758-65 (Nov 2000) ISSN: 0364-5134 [Print] United States
• PMID: 11079539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Myelin Basic Protein
• Peptide Fragments
• NBI 5788

Topics

• Adult
• Antibody Specificity (immunology)
• Cytokines (drug effects, immunology)
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Multiple Sclerosis (drug therapy, immunology, pathology)
• Myelin Basic Protein (administration & dosage, drug effects, immunology)
• Peptide Fragments (administration & dosage, pharmacology)
• T-Lymphocytes, Helper-Inducer (drug effects, immunology)