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The problems and promises of research into human immunology and autoimmune disease

Nature Medicine volume 18, pages 48–53 (2012)Cite this article

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Translational research in autoimmunity is hampered by a number of hurdles, including a lack of knowledge regarding initiating and pathologically relevant autoantigens, the low frequency of autoreactive pathogenic B and T cells, difficulty in accessing the affected tissue, differences between self-reactive and pathogen-specific lymphocytes, a lack of etiologically relevant preclinical animal models and the heterogeneity of disease presentation. Given the need for biomarkers and new therapeutics, it is imperative that these hurdles be surmounted.

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References

  1. Atkinson, M.A. & Leiter, E.H. Nat. Med. 5, 601–604 (1999).

    CAS  Google Scholar 

  2. Roep, B.O., Atkinson, M. & von Herrath, M. Nat. Rev. Immunol. 4, 989–997 (2004).

    CAS  Google Scholar 

  3. Steinman, L. & Zamvil, S.S. Ann. Neurol. 60, 12–21 (2006).

    CAS  PubMed Central  Google Scholar 

  4. Wu, H.J. et al. Immunity 32, 815–827 (2010).

    CAS  PubMed Central  Google Scholar 

  5. Yednock, T.A. et al. Nature 356, 63–66 (1992).

    CAS  Google Scholar 

  6. Siffrin, V. et al. Immunity 33, 424–436 (2010).

    CAS  Google Scholar 

  7. Aktas, O. et al. Neuron 46, 421–432 (2005).

    CAS  Google Scholar 

  8. Vogt, J. et al. Ann. Neurol. 66, 310–322 (2009).

    Google Scholar 

  9. Siffrin, V., Vogt, J., Radbruch, H., Nitsch, R. & Zipp, F. Trends Neurosci. 33, 202–210 (2010).

    CAS  Google Scholar 

  10. Pöllinger, B. et al. J. Exp. Med. 206, 1303–1316 (2009).

    Article  Google Scholar 

  11. Mestas, J. & Hughes, C.C. J. Immunol. 172, 2731–2738 (2004).

    CAS  PubMed Central  Google Scholar 

  12. Schulze-Topphoff, U. et al. Nat. Med. 15, 788–793 (2009).

    CAS  PubMed Central  Google Scholar 

  13. Sharpe, A.H. & Abbas, A.K. N. Engl. J. Med. 355, 973–975 (2006).

    CAS  Google Scholar 

  14. Huizinga, T.W. et al. Arthritis Rheum. 52, 3433–3438 (2005).

    CAS  Google Scholar 

  15. van der Helm-van Mil, A.H., Verpoort, K.N., Breedveld, F.C., Toes, R.E. & Huizinga, T.W. Arthritis Res. Ther. 7, R949–R958 (2005).

    CAS  PubMed Central  Google Scholar 

  16. Klareskog, L., Padyukov, L., Ronnelid, J. & Alfredsson, L. Curr. Opin. Immunol. 18, 650–655 (2006).

    CAS  Google Scholar 

  17. Sherry, N. et al. Lancet 378, 487–497 (2011).

    CAS  PubMed Central  Google Scholar 

  18. Orban, T. et al. Lancet 378, 412–419 (2011).

    CAS  PubMed Central  Google Scholar 

  19. Roep, B.O. Lancet 378, 376–378 (2011).

    Google Scholar 

  20. Cotsapas, C. et al. PLoS Genet. 7, e1002254 (2011).

    CAS  PubMed Central  Google Scholar 

  21. Martin, S. et al. N. Engl. J. Med. 345, 1036–1040 (2001).

    CAS  Google Scholar 

  22. Pescovitz, M.D. et al. N. Engl. J. Med. 361, 2143–2152 (2009).

    CAS  PubMed Central  Google Scholar 

  23. Hauser, S.L. et al. N. Engl. J. Med. 358, 676–688 (2008).

    CAS  Google Scholar 

  24. Coppieters, K.T. et al. J. Exp. Med. (in the press).

  25. Leray, E. et al. Brain 133, 1900–1913 (2010).

    PubMed Central  Google Scholar 

  26. Würfel, J. et al. Brain 127, 111–119 (2004).

    Google Scholar 

  27. Kaas, A. et al. Clin. Exp. Immunol. 161, 444–452 (2010).

    CAS  PubMed Central  Google Scholar 

  28. Paul, F. et al. PLoS Med. 4, e133 (2007).

    PubMed Central  Google Scholar 

  29. Toyka, K.V. et al. Science 190, 397–399 (1975).

    CAS  Google Scholar 

  30. Hinson, S.R. et al. J. Exp. Med. 205, 2473–2481 (2008).

    CAS  PubMed Central  Google Scholar 

  31. Gillard, P. et al. Diabetes Care 32, 1817–1819 (2009).

    CAS  PubMed Central  Google Scholar 

  32. Huurman, V.A. et al. PLoS ONE 3, e2435 (2008).

    PubMed Central  Google Scholar 

  33. Unger, W.W. et al. J. Autoimmun. 37, 151–159 (2011).

    CAS  Google Scholar 

  34. Wessels, J.A. et al. Arthritis Rheum. 56, 1765–1775 (2007).

    CAS  Google Scholar 

  35. Wandinger, K.P. et al. Lancet 361, 2036–2043 (2003).

    CAS  Google Scholar 

  36. Axtell, R.C. et al. Nat. Med. 16, 406–412 (2010).

    CAS  PubMed Central  Google Scholar 

  37. Farina, C. et al. Brain 124, 705–719 (2001).

    CAS  Google Scholar 

  38. Velthuis, J.H. et al. Diabetologia 52, 494–503 (2009).

    CAS  Google Scholar 

  39. van Halteren, A.G., Kardol, M.J., Mulder, A. & Roep, B.O. Diabetologia 48, 75–82 (2005).

    CAS  Google Scholar 

  40. Pinkse, G.G. et al. Proc. Natl. Acad. Sci. USA 102, 18425–18430 (2005).

    CAS  Google Scholar 

  41. Roep, B.O. & Peakman, M. Nat. Rev. Immunol. 10, 145–152 (2010).

    CAS  Google Scholar 

  42. Ouyang, Q. et al. Diabetes 55, 3068–3074 (2006).

    CAS  Google Scholar 

  43. Naik, R.G. et al. J. Autoimmun. 23, 55–61 (2004).

    CAS  Google Scholar 

  44. Reijonen, H. et al. Diabetes 51, 1375–1382 (2002).

    CAS  Google Scholar 

  45. Peterson, L.D., van der Keur, M., De Vries, R.R. & Roep, B.O. Diabetologia 42, 443–449 (1999).

    CAS  Google Scholar 

  46. Tree, T.I., Roep, B.O. & Peakman, M. Ann. NY Acad. Sci. 1079, 9–18 (2006).

    Google Scholar 

  47. Tree, T.I. et al. Diabetes 59, 1451–1460 (2010).

    CAS  PubMed Central  Google Scholar 

  48. Kenter, G.G. et al. N. Engl. J. Med. 361, 1838–1847 (2009).

    CAS  PubMed Central  Google Scholar 

  49. Davis, M.M., Altman, J.D. & Newell, E.W. Nat. Rev. Immunol. 11, 551–558 (2011).

    CAS  PubMed Central  Google Scholar 

  50. Bendall, S.C. et al. Science 332, 687–696 (2011).

    CAS  PubMed Central  Google Scholar 

  51. Velthuis, J.H. et al. Diabetes 59, 1721–1730 (2010).

    CAS  PubMed Central  Google Scholar 

  52. Matthews, J.B., Staeva, T.P., Bernstein, P.L., Peakman, M. & von Herrath, M. Clin. Exp. Immunol. 160, 176–184 (2010).

    CAS  PubMed Central  Google Scholar 

  53. Valle, A. et al. Diabetes 58, 875–881 (2009).

    CAS  PubMed Central  Google Scholar 

  54. Bos, W.H., Dijkmans, B.A., Boers, M., van de Stadt, R.J. & van Schaardenburg, D. Ann. Rheum. Dis. 69, 571–574 (2010).

    CAS  Google Scholar 

  55. Clayton, D.G. PLoS Genet. 5, e1000540 (2009).

    PubMed Central  Google Scholar 

  56. Sawcer, S., Ban, M., Wason, J. & Dudbridge, F. Ann. Neurol. 67, 3–10 (2010).

    CAS  PubMed Central  Google Scholar 

  57. Amagai, M., Tsunoda, K., Zillikens, D., Nagai, T. & Nishikawa, T. J. Am. Acad. Dermatol. 40, 167–170 (1999).

    CAS  Google Scholar 

  58. Li, N., Aoki, V., Hans-Filho, G., Rivitti, E.A. & Diaz, L.A. J. Exp. Med. 197, 1501–1510 (2003).

    CAS  PubMed Central  Google Scholar 

  59. Ioan-Facsinay, A. et al. Arthritis Rheum. 58, 3000–3008 (2008).

    Google Scholar 

  60. van de Stadt, L.A. et al. Arthritis Rheum. 63, 3226–3233 (2011).

    CAS  Google Scholar 

  61. van der Woude, D. et al. Ann. Rheum. Dis. 69, 1554–1561 (2010).

    CAS  Google Scholar 

  62. Willemze, A. et al. Ann. Rheum. Dis. published online doi:10.1136/annrheumdis-2011-200421 (13 October 2011).

  63. Bos, W.H. et al. Ann. Rheum. Dis. 69, 490–494 (2010).

    CAS  Google Scholar 

  64. Gale, E.A., Bingley, P.J., Emmett, C.L. & Collier, T. Lancet 363, 925–931 (2004).

    CAS  Google Scholar 

  65. Diabetes Prevention Trial—Type 1 Diabetes Study Group. N. Engl. J. Med. 346, 1685–1691 (2002).

  66. Voltarelli, J.C. et al. J. Am. Med. Assoc. 297, 1568–1576 (2007).

    CAS  Google Scholar 

  67. Hindorff, L.A. et al. Proc. Natl. Acad. Sci. USA 106, 9362–9367 (2009).

    CAS  PubMed Central  Google Scholar 

  68. The International Multiple Sclerosis Genetics Consortium (IMSGC) and the Wellcome Trust Case Control Consortium. Nature 476, 214–219 (2011).

  69. Maier, L.M. et al. PLoS Genet. 5, e1000322 (2009).

    PubMed Central  Google Scholar 

  70. Manolio, T.A. et al. Nature 461, 747–753 (2009).

    CAS  PubMed Central  Google Scholar 

  71. McCarthy, M.I. et al. Nat. Rev. Genet. 9, 356–369 (2008).

    CAS  Google Scholar 

  72. Oksenberg, J.R. & Baranzini, S.E. Nat. Rev. Neurol. 6, 429–437 (2010).

    Google Scholar 

  73. Ioannidis, J.P. PLoS Med. 2, e124 (2005).

    PubMed Central  Google Scholar 

  74. Heinig, M. et al. Nature 467, 460–464 (2010).

    CAS  PubMed Central  Google Scholar 

  75. Cortes, A. & Brown, M.A. Arthritis Res. Ther. 13, 101 (2011).

    PubMed Central  Google Scholar 

  76. Speliotes, E.K. et al. Nat. Genet. 42, 937–948 (2010).

    CAS  PubMed Central  Google Scholar 

  77. Lango Allen, H. et al. Nature 467, 832–838 (2010).

    CAS  PubMed Central  Google Scholar 

  78. Dendrou, C.A. et al. Nat. Genet. 41, 1011–1015 (2009).

    CAS  PubMed Central  Google Scholar 

  79. Long, S.A. et al. Diabetes 59, 407–415 (2010).

    CAS  Google Scholar 

  80. Craddock, N. et al. Nature 464, 713–720 (2010).

    CAS  PubMed Central  Google Scholar 

  81. The International Multiple Sclerosis Genetics Consortium (IMSGC). N. Engl. J. Med. 357, 851–862 (2007).

  82. Kemppinen, A., Sawcer, S. & Compston, A. Brief. Funct. Genomics 10, 61–70 (2011).

    CAS  Google Scholar 

  83. Gibson, G. Nat. Genet. 42, 558–560 (2010).

    CAS  Google Scholar 

  84. Rioux, J.D. et al. Nat. Genet. 39, 596–604 (2007).

    CAS  PubMed Central  Google Scholar 

  85. Nejentsev, S., Walker, N., Riches, D., Egholm, M. & Todd, J.A. Science 324, 387–389 (2009).

    CAS  PubMed Central  Google Scholar 

  86. Yang, J. et al. Nat. Genet. 42, 565–569 (2010).

    CAS  PubMed Central  Google Scholar 

  87. Roep, B.O. et al. Eur. J. Immunol. 26, 1285–1289 (1996).

    CAS  Google Scholar 

  88. De Grijse, J. et al. Diabetologia 53, 517–524 (2010).

    CAS  Google Scholar 

  89. Castaldo, P. et al. Curr. Drug Metab. 12, 278–286 (2011).

    CAS  Google Scholar 

  90. Bach, J.F. N. Engl. J. Med. 347, 911–920 (2002).

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunohaematology and Blood Transfusion, Bart O. Roep is at the Leiden University Medical Center, National Diabetes Expert Center, Leiden, The Netherlands.,

    Bart O Roep

  2. Jane Buckner is at the Translational Research Program, Benaroya Research Institute, Seattle, Washington, USA.,

    Jane Buckner

  3. Department of Clinical Neuroscience, Stephen Sawcer is at the University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.,

    Stephen Sawcer

  4. Rene Toes is at the Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.,

    Rene Toes

  5. Frauke Zipp is at the Klinik und Poliklinik für Neurologie, Universitätsmedizin Mainz (University Medical Center), Johannes-Gutenberg-Universität Mainz, Mainz, Germany.,

    Frauke Zipp

Authors
  1. Bart O Roep
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  4. Rene Toes
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Correspondence to Bart O Roep.

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Roep, B., Buckner, J., Sawcer, S. et al. The problems and promises of research into human immunology and autoimmune disease. Nat Med 18, 48–53 (2012). https://doi.org/10.1038/nm.2626

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