NBI-5788, an altered MBP83-93 peptide, induces a T-helper 2-like immune response in multiple sclerosis patients

We assessed the immune response induced in multiple sclerosis (MS) patients who had received NBI-5788, an altered peptide ligand (APL) designed from a n immunodominant region (83-99) of the neuroantigen myelin basic protein (M BP) (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 trea ted 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 w hole MBP-responsive T cells in MS patients treated with the APL was not sig nificantly 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-cel l lines from untreated MS patients. These results demonstrate that subcutan eous administration of a soluble APL based on the MBP peptide 83-99 in MS p atients can induce an APL-reactive immune response in which T lymphocytes c ross-reactive with the immunodominant neuroantigen MBP secrete anti-inflamm atory cytokines. The significant heterogeneity in immune response between i ndividuals indicates the need for clinical laboratory correlation during th e course of therapeutic trials.