Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'

Nils Landegren; Lindsey B Rosen; Eva Freyhult; Daniel Eriksson; Tove Fall; Gustav Smith; Elise M N Ferre; Petter Brodin; Donald Sharon; Michael Snyder; Michail Lionakis; Mark Anderson; Olle Kämpe

doi:10.7554/eLife.43578

Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'

Elife. 2019 Jun 27:8:e43578. doi: 10.7554/eLife.43578.

Authors

Nils Landegren^{1

2}, Lindsey B Rosen³, Eva Freyhult^{4

5}, Daniel Eriksson^{1

6}, Tove Fall⁷, Gustav Smith^{8

9

10}, Elise M N Ferre³, Petter Brodin^{8

11

12}, Donald Sharon¹³, Michael Snyder^{10

13}, Michail Lionakis³, Mark Anderson¹⁴, Olle Kämpe^{1

6

15}

Affiliations

¹ Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
² Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
³ Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
⁴ Department of Medical Sciences, National Bioinformatics Infrastructure, Uppsala, Sweden.
⁵ Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁶ Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
⁷ Department of Medical Sciences, Molecular Epidemiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁸ Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
⁹ Program in Medical and Population Genetics, Broad Institute of Harvard, Massachusetts Institute of Technology, Cambridge, United States.
¹⁰ Wallenberg Center for Molecular Medicine, Lund University Diabetes Center, Lund University, Lund, Sweden.
¹¹ Department of Women's and Children's Health, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
¹² Department of Newborn Medicine, Karolinska University Hospital, Stockholm, Sweden.
¹³ Department of Genetics, School of Medicine, Stanford University, Stanford, United States.
¹⁴ Diabetes Center, University of California, San Francisco, San Francisco, United States.
¹⁵ KG Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.

Abstract

The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.

Keywords: APS1/APECED; autoantibody; autoantigen; human; human biology; immune tolerance; immunology; inflammation; medicine; type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't
Comment

MeSH terms

Autoantibodies
Diabetes Mellitus, Type 1*
Humans
Interferon Type I*
Polyendocrinopathies, Autoimmune*
Transcription Factors

Substances

Autoantibodies
Interferon Type I
Transcription Factors

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.