Contributions
Abstract: EP1514
Type: ePoster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Interferon beta 1a/1b (IFN-β) is a first-line therapy for multiple sclerosis (MS). However, a significant number of treated patients develop neutralizing antibodies (NABs) against IFN-β, which reduce or abolish the efficacy of the drug. Antigen specific T helper cells are essential for the generation of sustained antibody responses to proteins. While antibody responses to IFN-β are well characterized, little is known about the T cell response to IFN-β.
Goals: To investigate the T cell response against IFN-β in MS patients who develop neutralizing antibodies.
Methods: T cell responses to IFN-β were mapped by split-well assay with peripheral blood mononuclear cells in a discovery cohort of 4 MS patients and 1 healthy donor. T cell experiments were performed with full length IFN-β proteins and synthesized 20-meric peptides overlapping by 15-aminoacids covering the entire sequence of IFN-β. T cell responses to immunodominant peptides and IFN-β proteins were investigated in additional 5 NABs positive and 5 NABs negative MS patients.
Results: We identified several immunodominant IFN-β epitopes that elicit T cell responses in patients and controls (aa 31-60, aa 141-170). Moreover, we observed a higher T cell response to IFN-β 1a/1b proteins in NAB positive versus NAB negative patients in two cohorts (p=0.0008 and p=0.008 respectively). Most of the IFN-β peptide specific T cell lines recognize IFN-β protein and most of the protein specific T cell lines recognize IFN-β peptides.
Conclusion: Our experiments demonstrate the occurrence of IFN-β 1a/1b protein and peptide specific
T cells in the blood of MS patients and controls. The T cell responses to IFN-β 1a/1b proteins and some immunodominant peptides are higher in NABs positive than NABs negative patients.
Disclosure:
Sudhakar Reddy Kalluri: Nothing to disclose
Zsuzsanna Hracsko: Nothing to disclose
Verena Grummel: Nothing to disclose
Viola Biberacher: Nothing to disclose
Verena Pernpeintner: Nothing to disclose
Dorothea Buck: D. Buck has received compensation for activities with Bayer HealthCare, BiogenIdec, MerckSerono, and Novartis. She is supported by the Abirisk Consortium
Bernhard Hemmer: has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and
T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralizing antibodies to interferon-beta.
Abstract: EP1514
Type: ePoster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Interferon beta 1a/1b (IFN-β) is a first-line therapy for multiple sclerosis (MS). However, a significant number of treated patients develop neutralizing antibodies (NABs) against IFN-β, which reduce or abolish the efficacy of the drug. Antigen specific T helper cells are essential for the generation of sustained antibody responses to proteins. While antibody responses to IFN-β are well characterized, little is known about the T cell response to IFN-β.
Goals: To investigate the T cell response against IFN-β in MS patients who develop neutralizing antibodies.
Methods: T cell responses to IFN-β were mapped by split-well assay with peripheral blood mononuclear cells in a discovery cohort of 4 MS patients and 1 healthy donor. T cell experiments were performed with full length IFN-β proteins and synthesized 20-meric peptides overlapping by 15-aminoacids covering the entire sequence of IFN-β. T cell responses to immunodominant peptides and IFN-β proteins were investigated in additional 5 NABs positive and 5 NABs negative MS patients.
Results: We identified several immunodominant IFN-β epitopes that elicit T cell responses in patients and controls (aa 31-60, aa 141-170). Moreover, we observed a higher T cell response to IFN-β 1a/1b proteins in NAB positive versus NAB negative patients in two cohorts (p=0.0008 and p=0.008 respectively). Most of the IFN-β peptide specific T cell lines recognize IFN-β protein and most of the protein specific T cell lines recognize IFN-β peptides.
Conclusion: Our experiments demonstrate the occurrence of IFN-β 1a/1b protein and peptide specific
T cells in the blood of MS patients and controls. The T cell responses to IFN-β 1a/1b proteins and some immunodominant peptides are higher in NABs positive than NABs negative patients.
Disclosure:
Sudhakar Reddy Kalluri: Nothing to disclose
Zsuzsanna Hracsko: Nothing to disclose
Verena Grummel: Nothing to disclose
Viola Biberacher: Nothing to disclose
Verena Pernpeintner: Nothing to disclose
Dorothea Buck: D. Buck has received compensation for activities with Bayer HealthCare, BiogenIdec, MerckSerono, and Novartis. She is supported by the Abirisk Consortium
Bernhard Hemmer: has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and
T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralizing antibodies to interferon-beta.