TY - JOUR
T1 - Autoreactive T-cell responses to myeloperoxidase in patients with antineutrophil cytoplasmic antibody-associated vasculitis and in healthy individuals
AU - Seta, Noriyuki
AU - Tajima, Michiko
AU - Kobayashi, Shigeto
AU - Kawakami, Yutaka
AU - Hashimoto, Hiroshi
AU - Kuwana, Masataka
N1 - Funding Information:
Acknowledgments This study was supported by grants from the Ministry of Health, Labour and Welfare of Japan.
PY - 2008
Y1 - 2008
N2 - The aim of this study was to evaluate the characteristics of autoreactive T cells to myeloperoxidase (MPO) in patients with MPO-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Peripheral blood T cells from 15 patients with MPO-ANCA-associated vasculitis and 14 healthy individuals were cultured with three recombinant proteins that together comprised the entire MPO sequence (L, all 112 amino acids (AA) of the light chain; HI, AA 1-227 of the heavy chain; HII, AA 212-467 of the heavy chain), and the antigen-specific T-cell proliferative response was measured by 3H-thymidine incorporation. T-cell responses to MPO-L and HI were both detected in four patients and three healthy donors, and responses to MPO-HII were detected in four patients and seven healthy donors. These findings indicate that at least three independent T-cell epitopes exist on the MPO molecule. Interestingly, the patients whose T cells showed these MPO-induced responses were mainly in remission. Peripheral blood T cells reactive with MPO were primarily of the HLA-DR-restricted CD4+ phenotype. In summary, we successfully used recombinant MPO fragments to detect autoreactive CD4+ T cells to multiple MPO epitopes in blood samples from patients with MPO-ANCA-associated vasculitis and healthy individuals.
AB - The aim of this study was to evaluate the characteristics of autoreactive T cells to myeloperoxidase (MPO) in patients with MPO-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Peripheral blood T cells from 15 patients with MPO-ANCA-associated vasculitis and 14 healthy individuals were cultured with three recombinant proteins that together comprised the entire MPO sequence (L, all 112 amino acids (AA) of the light chain; HI, AA 1-227 of the heavy chain; HII, AA 212-467 of the heavy chain), and the antigen-specific T-cell proliferative response was measured by 3H-thymidine incorporation. T-cell responses to MPO-L and HI were both detected in four patients and three healthy donors, and responses to MPO-HII were detected in four patients and seven healthy donors. These findings indicate that at least three independent T-cell epitopes exist on the MPO molecule. Interestingly, the patients whose T cells showed these MPO-induced responses were mainly in remission. Peripheral blood T cells reactive with MPO were primarily of the HLA-DR-restricted CD4+ phenotype. In summary, we successfully used recombinant MPO fragments to detect autoreactive CD4+ T cells to multiple MPO epitopes in blood samples from patients with MPO-ANCA-associated vasculitis and healthy individuals.
KW - ANCA-associated vasculitis
KW - MPO-reactive T cell
KW - Myeloperoxidase
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U2 - 10.1007/s10165-008-0109-1
DO - 10.1007/s10165-008-0109-1
M3 - Article
C2 - 18806928
AN - SCOPUS:57649149377
VL - 18
SP - 593
EP - 600
JO - Japanese Journal of Rheumatology
JF - Japanese Journal of Rheumatology
SN - 1439-7595
IS - 6
ER -