T cell response to Hu-D peptides in patients with anti-Hu syndrome.
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.
Rousseau
A
A
Department of Neurology and INSERM U495, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Benyahia
B
B
Dalmau
J
J
Connan
F
F
Guillet
J-G
JG
Delattre
J-Y
JY
Choppin
J
J
D018288:Carcinoma, Small Cell / Q000150:complications / Q000276:immunology*; D002478:Cells, Cultured; D051959:ELAV Proteins; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism; D020361:Paraneoplastic Syndromes, Nervous System / Q000150:complications / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D018709:Statistics, Nonparametric; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D051959:ELAV Proteins; D015234:HLA-A Antigens; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D007371:Interferon-gamma
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