Serological proteome analysis reveals new specific biases in the IgM and IgG autoantibody repertoires in autoimmune polyendocrine syndrome type 1

Article English OPEN
Dubucquoi, S. ; Proust-Lemoine, E. ; Kemp, E.H. ; Ryndak, A. ; Lefèvre-Dutoit, V. ; Bellart, M. ; Saugier-Véber, P. ; Duban-Deweer, S. ; Wémeau, J.L. ; Prin, L. ; Lefranc, D. (2015)
  • Publisher: Taylor & Francis

Objective: Autoimmune polyendocrine syndrome type 1 (APS 1) is caused by mutations in the AIRE gene that induce intrathymic T-cell tolerance breakdown, which results in tissue-specific autoimmune diseases. \ud \ud Design: To evaluate the effect of a well-defined T-cell repertoire impairment on humoral self-reactive fingerprints, comparative serum self-IgG and self-IgM reactivities were analyzed using both one- and two-dimensional western blotting approaches against a broad spectrum of peripheral tissue antigens. Methods: Autoantibody patterns of APS 1 patients were compared with those of subjects affected by other autoimmune endocrinopathies (OAE) and healthy controls. \ud \ud Results: Using a Chi-square test, significant changes in the Ab repertoire were found when intergroup patterns were compared. A singular distortion of both serum self-IgG and self-IgM repertoires was noted in APS 1 patients. The molecular characterization of these antigenic targets was conducted using a proteomic approach. In this context, autoantibodies recognized more significantly either tissue-specific antigens, such as pancreatic amylase, pancreatic triacylglycerol lipase and pancreatic regenerating protein 1α, or widely distributed antigens, such as peroxiredoxin-2, heat shock cognate 71-kDa protein and aldose reductase. As expected, a well-defined self-reactive T-cell repertoire impairment, as described in APS 1 patients, affected the tissue-specific self-IgG repertoire. Interestingly, discriminant IgM reactivities targeting both tissue-specific and more widely expressed antigens were also specifically observed in APS 1 patients. Using recombinant targets, we observed that post translational modifications of these specific antigens impacted upon their recognition. \ud \ud Conclusions: The data suggest that T-cell-dependent but also T-cell-independent mechanisms are involved in the dynamic evolution of autoimmunity in APS 1.
  • References (40)
    40 references, page 1 of 4

    1. Aaltonen, J., P. Björses, J. Perheentupa, N. Horelli Kuitunen, A. Palotie, L. Peltonen, Y. S. Lee, F. Francis, S. Henning, C. Thiel, H. Leharach, and M. Yaspo. 1997. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet 17: 399 403.

    2. Nagamine, K., P. Peterson, H. S. Scott, J. Kudoh, S. Minoshima, M. Heino, K. J. Krohn, M. D. Lalioti, P. E. Mullis, S. E. Antonarakis, K. Kawasaki, S. Asakawa, F. Ito, and N. Shimizu. 1997. Positional cloning of the APECED gene. Nat. Genet. 17: 393 398.

    3. Gardner, J. M., J. J. Devoss, R. S. Friedman, D. J. Wong, Y. X. Tan, X. Zhou, K. P. Johannes, M. A. Su, H. Y. Chang, M. F. Krummel, and M. S. Anderson. 2008. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 321: 843 847.

    4. Pitkänen, J., P. Vähämurto, K. Krohn, and P. Peterson. 2001. Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain. J. Biol. Chem. 276: 19597 19602.

    5. Anderson, M. S., E. S. Venanzi, L. Klein, Z. Chen, S. P. Berzins, S. J. Turley, H. von Boehmer, R. Bronson, A. Dierich, C. Benoist, and D. Mathis. 2002. Projection of an immunological self shadow within the thymus by the aire protein. Science 298: 1395 1401.

    6. Ramsey, C., O. Winqvist, L. Puhakka, M. Halonen, A. Moro, O. Kämpe, P. Eskelin, M. PeltoHuikko, and L. Peltonen. 2002. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum. Mol. Genet. 11: 397 409.

    7. Gavanescu, I., B. Kessler, H. Ploegh, C. Benoist, and D. Mathis. 2007. Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity. Proc. Natl. Acad. Sci. U.S.A. 104: 4583 4587.

    8. Suzuki, E., Y. Kobayashi, O. Kawano, K. Endo, H. Haneda, H. Yukiue, H. Sasaki, M. Yano, M. Maeda, and Y. Fujii. 2008. Expression of AIRE in thymocytes and peripheral lymphocytes. Autoimmunity 41: 133 139.

    9. Ahonen, P., S. Myllärniemi, I. Sipilä, and J. Perheentupa. 1990. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N. Engl. J. Med. 322: 1829 1836.

    10. Perniola, R., A. Falorni, M. G. Clemente, F. Forini, E. Accogli, and G. Lobreglio. 2000. Organspecific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Eur. J. Endocrinol. 143: 497 503.

  • Metrics
    views in OpenAIRE
    views in local repository
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    White Rose Research Online - IRUS-UK 0 7
Share - Bookmark