Evidence map›Paper›PMID 27426947›Full record

ArticleCell2016

AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies.

Steffen Meyer, Martin Woodward, Christina Hertel, Philip Vlaicu, Yasmin Haque, Jaanika Kärner, Annalisa Macagno, Shimobi C Onuoha, Dmytro Fishman, Hedi Peterson and 11 more

Abstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

172 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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  4. Trial
  5. Article
  6. Article
  7. High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  18. T follicular helper cells in primary immune regulatory disorders.The Journal of allergy and clinical immunology · 2025
    Review
  19. Article
  20. Article

112 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Steffen MeyerImmunoQure AG, Königsallee 90, 2012 Düsseldorf, Germany.
Martin WoodwardPeter Gorer Department of Immunobiology, King's College, London SE19RT, UK.
Christina HertelImmunoQure AG, Königsallee 90, 2012 Düsseldorf, Germany.
Philip VlaicuImmunoQure AG, Königsallee 90, 2012 Düsseldorf, Germany.
Yasmin HaquePeter Gorer Department of Immunobiology, King's College, London SE19RT, UK.
Jaanika KärnerMolecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
Annalisa MacagnoImmunoQure Research AG, Wagistrasse 14, 8952 Schlieren, Switzerland.
Shimobi C OnuohaImmunoQure Research AG, Wagistrasse 14, 8952 Schlieren, Switzerland.
Dmytro FishmanInstitute of Computer Science, University of Tartu, Liivi 2, Tartu 50409, Estonia; Quretec Ltd., Ülikooli 6A, Tartu 51003, Estonia.
Hedi PetersonInstitute of Computer Science, University of Tartu, Liivi 2, Tartu 50409, Estonia; Quretec Ltd., Ülikooli 6A, Tartu 51003, Estonia.
Kaja MetskülaDepartment of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
Raivo UiboDepartment of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
Kirsi JänttiClinical Research Institute HUCH Ltd., Haartmaninkatu 8, 00290 Helsinki, Finland.
Kati HokynarClinical Research Institute HUCH Ltd., Haartmaninkatu 8, 00290 Helsinki, Finland.
Anette S B WolffDepartment of Clinical Science, University of Bergen, Laboratory Building, 8th floor, 5021 Bergen, Norway.
APECED patient collaborative
Kai KrohnClinical Research Institute HUCH Ltd., Haartmaninkatu 8, 00290 Helsinki, Finland.
Annamari RankiDepartment of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, Skin and Allergy Hospital, Helsinki University Central Hospital, Meilahdentie 2, 00250 Helsinki, Finland.
Pärt PetersonMolecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
Kai KisandMolecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia. Electronic address: kai.kisand@ut.ee.
Adrian HaydayPeter Gorer Department of Immunobiology, King's College, London SE19RT, UK. Electronic address: adrian.hayday@kcl.ac.uk.

Funding

Wellcome Trust
6 · The paper itself

Abstract

APS1/APECED patients are defined by defects in the autoimmune regulator (AIRE) that mediates central T cell tolerance to many self-antigens. AIRE deficiency also affects B cell tolerance, but this is incompletely understood. Here we show that most APS1/APECED patients displayed B cell autoreactivity toward unique sets of approximately 100 self-proteins. Thereby, autoantibodies from 81 patients collectively detected many thousands of human proteins. The loss of B cell tolerance seemingly occurred during antibody affinity maturation, an obligatorily T cell-dependent step. Consistent with this, many APS1/APECED patients harbored extremely high-affinity, neutralizing autoantibodies, particularly against specific cytokines. Such antibodies were biologically active in vitro and in vivo, and those neutralizing type I interferons (IFNs) showed a striking inverse correlation with type I diabetes, not shown by other anti-cytokine antibodies. Thus, naturally occurring human autoantibodies may actively limit disease and be of therapeutic utility.

Indexed as

Antibody AffinityAdolescentAdultAgedAIRE ProteinAnimalsAntibodies, NeutralizingAutoantibodiesChildChild, PreschoolCytokinesDiabetes Mellitus, Type 1Disease ResistanceHumansImmune ToleranceMice, Inbred C57BLAIRE ProteinAntibodies, NeutralizingAutoantibodiesCytokinesTranscription Factors

Identifiers

PMID27426947
PMCPMC4967814

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.