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Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'

In 2016, we reported four substantial observations of APECED/APS1 patients, who are deficient in AIRE, a major regulator of central T cell tolerance (Meyer et al., 2016). Two of those observations have been challenged. Specifically, ‘private’ autoantibody reactivities shared by only a few patients b...

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Autores principales: Hertel, Christina, Fishman, Dmytro, Lorenc, Anna, Ranki, Annamari, Krohn, Kai, Peterson, Pärt, Kisand, Kai, Hayday, Adrian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597236/
https://www.ncbi.nlm.nih.gov/pubmed/31244472
http://dx.doi.org/10.7554/eLife.45826
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author Hertel, Christina
Fishman, Dmytro
Lorenc, Anna
Ranki, Annamari
Krohn, Kai
Peterson, Pärt
Kisand, Kai
Hayday, Adrian
author_facet Hertel, Christina
Fishman, Dmytro
Lorenc, Anna
Ranki, Annamari
Krohn, Kai
Peterson, Pärt
Kisand, Kai
Hayday, Adrian
author_sort Hertel, Christina
collection PubMed
description In 2016, we reported four substantial observations of APECED/APS1 patients, who are deficient in AIRE, a major regulator of central T cell tolerance (Meyer et al., 2016). Two of those observations have been challenged. Specifically, ‘private’ autoantibody reactivities shared by only a few patients but collectively targeting >1000 autoantigens have been attributed to false positives (Landegren, 2019). While acknowledging this risk, our study-design included follow-up validation, permitting us to adopt statistical approaches to also limit false negatives. Importantly, many such private specificities have now been validated by multiple, independent means including the autoantibodies’ molecular cloning and expression. Second, a significant correlation of antibody-mediated IFNα neutralization with an absence of disease in patients highly disposed to Type I diabetes has been challenged because of a claimed failure to replicate our findings (Landegren, 2019). However, flaws in design and implementation invalidate this challenge. Thus, our results present robust, insightful, independently validated depictions of APECED/APS1, that have spawned productive follow-up studies.
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spelling pubmed-65972362019-06-28 Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies' Hertel, Christina Fishman, Dmytro Lorenc, Anna Ranki, Annamari Krohn, Kai Peterson, Pärt Kisand, Kai Hayday, Adrian eLife Human Biology and Medicine In 2016, we reported four substantial observations of APECED/APS1 patients, who are deficient in AIRE, a major regulator of central T cell tolerance (Meyer et al., 2016). Two of those observations have been challenged. Specifically, ‘private’ autoantibody reactivities shared by only a few patients but collectively targeting >1000 autoantigens have been attributed to false positives (Landegren, 2019). While acknowledging this risk, our study-design included follow-up validation, permitting us to adopt statistical approaches to also limit false negatives. Importantly, many such private specificities have now been validated by multiple, independent means including the autoantibodies’ molecular cloning and expression. Second, a significant correlation of antibody-mediated IFNα neutralization with an absence of disease in patients highly disposed to Type I diabetes has been challenged because of a claimed failure to replicate our findings (Landegren, 2019). However, flaws in design and implementation invalidate this challenge. Thus, our results present robust, insightful, independently validated depictions of APECED/APS1, that have spawned productive follow-up studies. eLife Sciences Publications, Ltd 2019-06-27 /pmc/articles/PMC6597236/ /pubmed/31244472 http://dx.doi.org/10.7554/eLife.45826 Text en © 2019, Hertel et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Human Biology and Medicine
Hertel, Christina
Fishman, Dmytro
Lorenc, Anna
Ranki, Annamari
Krohn, Kai
Peterson, Pärt
Kisand, Kai
Hayday, Adrian
Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
title Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
title_full Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
title_fullStr Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
title_full_unstemmed Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
title_short Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
title_sort response to comment on 'aire-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
topic Human Biology and Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597236/
https://www.ncbi.nlm.nih.gov/pubmed/31244472
http://dx.doi.org/10.7554/eLife.45826
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