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Autoreactive T-cell responses to myeloperoxidase in patients with antineutrophil cytoplasmic antibody-associated vasculitis and in healthy individuals

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Modern Rheumatology

Abstract

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.

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Acknowledgments

This study was supported by grants from the Ministry of Health, Labour and Welfare of Japan.

Conflicts of interest statement

The authors declare that there are no conflicts of interest associated with this article.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Noriyuki Seta & Masataka Kuwana

  2. Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan

    Michiko Tajima, Shigeto Kobayashi & Hiroshi Hashimoto

  3. Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan

    Yutaka Kawakami

Authors
  1. Noriyuki Seta
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  2. Michiko Tajima
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  3. Shigeto Kobayashi
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  4. Yutaka Kawakami
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  5. Hiroshi Hashimoto
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  6. Masataka Kuwana
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Correspondence to Masataka Kuwana.

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Seta, N., Tajima, M., Kobayashi, S. et al. Autoreactive T-cell responses to myeloperoxidase in patients with antineutrophil cytoplasmic antibody-associated vasculitis and in healthy individuals. Mod Rheumatol 18, 593–600 (2008). https://doi.org/10.1007/s10165-008-0109-1

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  • DOI: https://doi.org/10.1007/s10165-008-0109-1

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