Autoreactive T-cell responses to myeloperoxidase in patients with antineutrophil cytoplasmic antibody-associated vasculitis and in healthy individuals.
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.
Seta
Noriyuki
N
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Tajima
Michiko
M
Kobayashi
Shigeto
S
Kawakami
Yutaka
Y
Hashimoto
Hiroshi
H
Kuwana
Masataka
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014657:Vasculitis / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D009195:Peroxidase