Journal of Clinical Immunology

, Volume 32, Issue 2, pp 230–237

Radioligand-Binding Assay Reveals Distinct Autoantibody Preferences for Type I Interferons in APS I and Myasthenia Gravis Subgroups

  • Liv Hapnes
  • Nick Willcox
  • Bergithe E. V. Oftedal
  • Jone F. Owe
  • Nils Erik Gilhus
  • Anthony Meager
  • Eystein S. Husebye
  • Anette S. Bøe Wolff
Article

DOI: 10.1007/s10875-011-9617-4

Cite this article as:
Hapnes, L., Willcox, N., Oftedal, B.E.V. et al. J Clin Immunol (2012) 32: 230. doi:10.1007/s10875-011-9617-4
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Abstract

Patients with autoimmune polyendocrine syndrome type I (APS I) or acquired thymoma-associated myasthenia gravis (MG) surprisingly share several common features, including defective expression of the transcription factor AIRE and autoantibodies against type I interferons. Here, we have adapted and validated the radioligand-binding assay we recently developed against 35S-Met-interferon-ω, for rapid and specific screening for autoantibodies against interferons-α2 and -α8. We then investigated their potential for diagnosis and for predicting clinical manifestations in patients with APS I and different subgroups of MG. Autoantibodies against interferons-ω, -α2, and -α8 occurred more often in patients with APS I (100%) and MG with thymoma (73%) than in late-onset MG (39%) and early-onset MG (5%). These autoantibodies showed preferences for interferon-ω in APS I and for the interferon-αs in MG, hinting at thymic aberrations in both groups. The exact profile of type I interferon antibodies may indicate MG subtype and may hint at thymoma recurrence.

Keywords

Autoimmunity type I interferons autoimmune polyendocrine syndrome type I APECED thymoma myasthenia gravis late-onset MG AIRE 

Abbreviations

AD

Addison’s Disease

AIRE

Autoimmune regulator

APS I

Autoimmune polyendocrine syndrome type I

autoAbs

Autoantibodies

HP

Hypoparathyroidism

CMC

Chronic mucocutaneous candidiasis

ELISA

Enzyme-linked immunosorbent assay

RLBA

Radioligand-binding assay

Supplementary material

10875_2011_9617_Fig3_ESM.jpg (83 kb)
Supplementary Figure 1

Comparison of indices from radioligand-binding assay (RLBA) with titres from interferon antiviral neutralization assays against type I IFNs for late-onset MG and thymoma-associated MG patients. Some late-onset MG and thymoma-associated MG sera had previously been analyzed by antiviral neutralization assays; for clarity, they are grouped by neutralization titer: 0 = titer < 100; 1 = titer 100–1,000, 2 = titer 1,000–100,000, 3 = titre > 100,000. Thresholds for positivity for RLBA are given by a black horizontal line in each plot. Correlation between the assays was calculated by Spearman's correlation test in Graphpad 5.02. *0.05 < P > 0.01 statistically significant correlation; **P < 0.001 statistically significant correlation; (JPEG 83 kb)

10875_2011_9617_MOESM1_ESM.tif (100.7 mb)
High resolution image file (TIFF 103085 kb)
10875_2011_9617_Fig4_ESM.jpg (34 kb)
Supplementary Figure 2

Binding indices of autoAbs against type I IFNs in late-onset MG, thymoma-associated MG, and autoimmune polyendocrine syndrome type I (APS I) for the patients who did not have antibodies to all of the three IFNs (JPEG 34 kb)

10875_2011_9617_MOESM2_ESM.tif (39.4 mb)
High resolution iamge file (TIFF 40344 kb)
10875_2011_9617_MOESM3_ESM.pdf (38 kb)
Supplementary Table 1(PDF 38 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Liv Hapnes
    • 1
  • Nick Willcox
    • 2
  • Bergithe E. V. Oftedal
    • 1
    • 3
  • Jone F. Owe
    • 4
    • 5
  • Nils Erik Gilhus
    • 4
    • 5
  • Anthony Meager
    • 6
  • Eystein S. Husebye
    • 1
    • 3
  • Anette S. Bøe Wolff
    • 1
    • 7
  1. 1.Institute of MedicineUniversity of BergenBergenNorway
  2. 2.Neuroscience Group, Weatherall Institute of Molecular MedicineUniversity of OxfordOxfordUK
  3. 3.Department of MedicineHaukeland University HospitalBergenNorway
  4. 4.Department of NeurologyHaukeland University HospitalBergenNorway
  5. 5.Department of Clinical MedicineUniversity of BergenBergenNorway
  6. 6.BiotherapeuticsThe National Institute for Biological Standards and ControlSouth MimmsUK
  7. 7.Department of Endocrinoloy, Institute of MedicineUniversity of BergenBergenNorway

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