LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
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
Languages: English
Types: Article
Subjects:
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.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 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.
    • 11. Laakso, S. M., E. Kekäläinen, N. Heikkilä, H. Mannerström, K. Kisand, P. Peterson, A. Ranki, and T. P. Arstila. 2014. In vivo analysis of helper T cell responses in patients with autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy provides evidence in support of an IL-22 defect. Autoimmunity 47: 556 562.
    • 12. Kemp, E. H., M. Habibullah, N. Kluger, A. Ranki, H. K. Sandhu, K. J. E. Krohn, and A. P. Weetman. 2014. Prevalence and clinical associations of calcium-sensing receptor and NALP5 autoantibodies in Finnish APECED patients. J. Clin. Endocrinol. Metab. 99: 1064 1071.
    • 13. Lefranc, D., L. Almeras, S. Dubucquoi, J. de Seze, P. Vermersch, and L. Prin. 2004. Distortion of the self-reactive IgG antibody repertoire in multiple sclerosis as a new diagnostic tool. J. Immunol. 172: 669 678.
    • 14. Almeras, L., D. Lefranc, H. Drobecq, J. de Seze, S. Dubucquoi, P. Vermersch, and L. Prin. 2004. New antigenic candidates in multiple sclerosis: identification by serological proteome analysis. Proteomics 4: 2184 2194.
    • 15. Lefranc, D., D. Launay, S. Dubucquoi, J. de Seze, P. Dussart, M. Vermersch, E. Hachulla, P.-Y. Hatron, P. Vermersch, L. Mouthon, and L. Prin. 2007. Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach. Arthritis Rheum. 56: 3420 3432.
    • 16. Mouthon, L., M. Haury, S. Lacroix-Desmazes, C. Barreau, A. Coutinho, and M. D. Kazatchkine. 1995. Analysis of the normal human IgG antibody repertoire. Evidence that IgG autoantibodies of healthy adults recognize a limited and conserved set of protein antigens in homologous tissues. J. Immunol. 154: 5769 5778.
    • 17. Neufeld, M., N. Maclaren, and R. Blizzard. 1980. Autoimmune polyglandular syndromes. Pediatr Ann 9: 154 162.
    • 18. Saugier-Veber, P., N. Drouot, L. M. Wolf, J. M. Kuhn, T. Frébourg, and H. Lefebvre. 2001. Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Eur. J. Endocrinol. 144: 347 351.
    • 19. Maurice, P., A. M. Daulat, C. Broussard, J. Mozo, G. Clary, F. Hotellier, P. Chafey, J.-L. Guillaume, G. Ferry, J. A. Boutin, P. Delagrange, L. Camoin, and R. Jockers. 2008. A generic approach for the purification of signaling complexes that specifically interact with the carboxylterminal domain of G protein-coupled receptors. Mol. Cell Proteomics 7: 1556 1569.
    • 20. Popler, J., M. Alimohammadi, O. Kämpe, F. Dalin, M. K. Dishop, J. M. Barker, M. MoriartyKelsey, J. B. Soep, and R. R. Deterding. 2012. Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab. Pediatr. Pulmonol. 47: 84 87.
    • 21. Avrameas, S., and T. Ternynck. 1995. Natural autoantibodies: the other side of the immune system. Res. Immunol. 146: 235 248.
    • 22. Taylor, J. J., M. K. Jenkins, and K. A. Pape. 2012. Heterogeneity in the differentiation and function of memory B cells. Trends Immunol. 33: 590 597.
    • 23. Pillai, S., A. Cariappa, and S. T. Moran. 2005. Marginal zone B cells. Annu. Rev. Immunol. 23: 161 196.
    • 24. Weill, J.-C., S. Weller, and C.-A. Reynaud. 2009. Human marginal zone B cells. Annu. Rev. Immunol. 27: 267 285.
    • 25. Niki, S., K. Oshikawa, Y. Mouri, F. Hirota, A. Matsushima, M. Yano, H. Han, Y. Bando, K. Izumi, M. Matsumoto, K. I. Nakayama, N. Kuroda, and M. Matsumoto. 2006. Alteration of intrapancreatic target-organ specificity by abrogation of Aire in NOD mice. J. Clin. Invest. 116: 1292 1301.
    • 26. Martin, F., and J. F. Kearney. 2000. Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk. Immunity 12: 39 49.
    • 27. Ramsey, C., S. Hässler, P. Marits, O. Kämpe, C. D. Surh, L. Peltonen, and O. Winqvist. 2006. Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur. J. Immunol. 36: 305 317.
    • 28. Lindh, E., S. M. Lind, E. Lindmark, S. Hässler, J. Perheentupa, L. Peltonen, O. Winqvist, and M. C. I. Karlsson. 2008. AIRE regulates T-cell-independent B-cell responses through BAFF. Proc. Natl. Acad. Sci. U.S.A. 105: 18466 18471.
    • 29. Perheentupa, J. 2006. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J. Clin. Endocrinol. Metab. 91: 2843 2850.
    • 30. Proust-Lemoine, E., P. Saugier-Veber, H. Lefebvre, D. Lefranc, L. Prin, J. Weill, J.-C. Carel, and J.-L. Wemeau. 2010. [Autoimmune polyendocrine syndrome type 1]. Arch Pediatr 17: 597 598.
    • 31. Ekwall, O., H. Hedstrand, L. Grimelius, J. Haavik, J. Perheentupa, J. Gustafsson, E. Husebye, O. Kämpe, and F. Rorsman. 1998. Identification of tryptophan hydroxylase as an intestinal autoantigen. Lancet 352: 279 283.
    • 32. Sköldberg, F., G. M. Portela-Gomes, L. Grimelius, G. Nilsson, J. Perheentupa, C. Betterle, E. S. Husebye, J. Gustafsson, A. Rönnblom, F. Rorsman, and O. Kämpe. 2003. Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells. J. Clin. Endocrinol. Metab. 88: 1445 1452.
    • 33. Ward, L., J. Paquette, E. Seidman, C. Huot, F. Alvarez, P. Crock, E. Delvin, O. Kämpe, and C. Deal. 1999. Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J. Clin.
    • 34. Högenauer, C., R. L. Meyer, G. J. Netto, D. Bell, K. H. Little, L. Ferries, C. A. Santa Ana, J. L. Porter, and J. S. Fordtran. 2001. Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type I. N. Engl. J. Med. 344: 270 274.
    • 35. Scirè, G., F. M. Magliocca, S. Cianfarani, A. Scalamandrè, V. Petrozza, and M. Bonamico. 1991. Autoimmune polyendocrine candidiasis syndrome with associated chronic diarrhea caused by intestinal infection and pancreas insufficiency. J. Pediatr. Gastroenterol. Nutr. 13: 224 227.
    • 36. Jiang, W., M. S. Anderson, R. Bronson, D. Mathis, and C. Benoist. 2005. Modifier loci condition autoimmunity provoked by Aire deficiency. J. Exp. Med. 202: 805 815.
    • 37. Grimshaw, C. E., and E. J. Mathur. 1989. Immunoquantitation of aldose reductase in human tissues. Anal. Biochem. 176: 66 71.
    • 38. Karasawa, R., S. Ozaki, K. Nishioka, and T. Kato. 2005. Autoantibodies to peroxiredoxin I and IV in patients with systemic autoimmune diseases. Microbiol. Immunol. 49: 57 65.
    • 39. Iwata, Y., F. Ogawa, K. Komura, E. Muroi, T. Hara, K. Shimizu, M. Hasegawa, M. Fujimoto, Y. Tomita, and S. Sato. 2007. Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress. Rheumatology (Oxford) 46: 790 795.
    • 40. Iizuka, N., K. Okamoto, R. Matsushita, M. Kimura, K. Nagai, M. Arito, M. S. Kurokawa, K. Masuko, N. Suematsu, S. Hirohata, and T. Kato. 2010. Identification of autoantigens specific for systemic lupus erythematosus with central nervous system involvement. Lupus 19: 717 726.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article