T cell response to Hu-D peptides in patients with anti-Hu syndrome

• Published in: Journal of neuro-oncology Vol. 71; no. 3; pp. 231 - 236
• Main Authors: Rousseau, A., Benyahia, B., Dalmau, J., Connan, F., Guillet, J. -G., Delattre, J. -Y., Choppin, J.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.02.2005; Springer Nature B.V
• Subjects: Biological and medical sciences; Carcinoma, Small Cell - complications; Carcinoma, Small Cell - immunology; Cells, Cultured; Development. Senescence. Regeneration. Transplantation; ELAV Proteins; Fundamental and applied biological sciences. Psychology; HLA-A Antigens - immunology; HLA-A Antigens - metabolism; Humans; Immunity, Cellular - immunology; Interferon-gamma - metabolism; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - metabolism; Neurology; Paraneoplastic Syndromes, Nervous System - complications; Paraneoplastic Syndromes, Nervous System - immunology; Peptide Fragments - immunology; RNA-Binding Proteins - immunology; RNA-Binding Proteins - metabolism; Statistics, Nonparametric; Syndrome; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Vertebrates: nervous system and sense organs; Human; T lymphocytes; anti-Hu syndrome; HLA-System; Nervous system diseases; Hu-D epitopes; Antigenic determinant; Peptides; paraneoplastic disorders; Cellular immunity; T-Lymphocyte; IFN-y; Paraneoplastic syndrome; ELISPOT assay; HLA/peptide complexes
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-004-1723-1

The anti-Hu syndrome is the most common paraneoplastic neurologic syndrome but the exact mechanism of immune mediated neuronal injury remains unknown. Anti-Hu antibodies do not appear to play a pivotal role in the pathogenesis of the disease. To assess cell-mediated immunity, we selected 51 peptides from the Hu-D sequence and tested their ability to bind to six common HLA class I molecules. Stable complexes with purified HLA molecules were obtained with 19/51 (37%) selected peptides. Subsequently, the ability of the 19 HLA-binding peptides to stimulate T cells from 10 patients and 10 control subjects was evaluated by detecting IFN-gamma secretion. An anti-peptide T-cell response was observed in 7/10 Hu-positive patients but also in 3/10 control subjects. Overall, a significant T-cell activation occurred in response to 74% (14 out of 19) of the selected peptides in the Hu-positive patients vs. 16% (3 out of 19) in the control group (p < 0.001). In addition, T cells of patients tested within 3 months of the onset of anti-Hu syndrome responded to 82% (14 out of 17) of assessed Hu-D peptides vs. 37% (7 out of 19) in patients tested 1 year or more after developing the syndrome (p < 0.01). Thus, the present study suggests a role of cellular immunity during the course of anti-Hu syndrome.