University of Oulu

Hautala, Timo MD, PhD*,†; Vähäsalo, Paula MD, PhD‡; Kuismin, Outi MD, PhD§; Keskitalo, Salla PhD∥; Rajamäki, Kristiina PhD¶; Väänänen, Antti MD#; Simojoki, Marja MD**; Säily, Marjaana MD, PhD*; Pelkonen, Ilpo MD††; Tokola, Heikki MD, PhD‡‡; Mäkinen, Markus MD, PhD‡‡; Kaarteenaho, Riitta MD, PhD§§; Jartti, Airi MD, PhD∥∥; Hautala, Nina MD, PhD¶¶; Kantola, Saara MD##; Jackson, Päivi MD***; Glumoff, Virpi PhD†; Saarela, Janna MD, PhD†††; Varjosalo, Markku PhD∥,‡‡‡; Eklund, Kari K. MD, PhD§§§; Seppänen, Mikko R. J. MD, PhD¶,∥∥∥ A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment, JCR: Journal of Clinical Rheumatology: January 21, 2020 - Volume Publish Ahead of Print - Issue - doi: 10.1097/RHU.0000000000001268

A family with A20 haploinsufficiency presenting with novel clinical manifestations and challenges for treatment

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Author: Hautala, Timo1,2; Vähäsalo, Paula3; Kuismin, Outi4;
Organizations: 1Department of Internal Medicine, Oulu University Hospital, Oulu, Finland
2Research Unit of Biomedicine, University of Oulu, Oulu, Finland
3Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
4Department of Clinical Genetics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
5Institute of Biotechnology, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
6Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
7Department of Infection Control, Lapland Central Hospital, Rovaniemi, Finland
8Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
9Hematology Laboratory, Nordlab Oulu, Oulu University Hospital, Oulu, Finland
10Department of Pathology, Cancer Research and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland
11Respiratory Medicine, Research Unit of Internal Medicine, University of Oulu and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
12Department of Radiology, Oulu University Hospital, Oulu, Finland
13Department of Ophthalmology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
14Department of Dentistry, Oulu University Hospital, Oulu, Finland
15Department of Dermatology, Oulu University Hospital, Oulu, Finland
16Institute for Molecular Medicine Finland, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
17Proteomics Unit, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
18Department of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University Hospital. Research Institute, Invalid Foundation. Orton Orthopedic Hospital, Helsinki, Finland
19Rare Diseases Center and Pediatric Research Center, Children and Adolescents and Adult Immunodeficiency Unit, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020100778342
Language: English
Published: Wolters Kluwer, 2020
Publish Date: 2021-01-21
Description:

Abstract

Background: Tumor necrosis factor α–induced protein 3 gene (TNFAIP3, also called A20) haploinsufficiency (HA20) leads to autoinflammation and autoimmunity. We have recently shown that a p.(Lys91*) mutation in A20 disrupts nuclear factor κB signaling, impairs protein-protein interactions of A20, and leads to inflammasome activation.

Methods: We now describe the clinical presentations and drug responses in a family with HA20 p.(Lys91*) mutation, consistent with our previously reported diverse immunological and functional findings.

Results: We report for the first time that inflammasome-mediated autoinflammatory lung reaction caused by HA20 can be treated with interleukin 1 antagonist anakinra. We also describe severe anemia related to HA20 successfully treated with mycophenolate. In addition, HA20 p.(Lys91*) was found to associate with autoimmune thyroid disease, juvenile idiopathic arthritis, psoriasis, liver disease, and immunodeficiency presenting with specific antibody deficiency and genital papillomatosis.

Conclusions: We conclude that HA20 may lead to combination of inflammation, immunodeficiency, and autoimmunity. The condition may present with variable and unpredictable symptoms with atypical treatment responses.

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Series: JCR. Journal of clinical rheumatology
ISSN: 1076-1608
ISSN-E: 1536-7355
ISSN-L: 1076-1608
Volume: In press
DOI: 10.1097/RHU.0000000000001268
OADOI: https://oadoi.org/10.1097/RHU.0000000000001268
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: Funding was provided by Oulu and Helsinki University Hospital Research Funds.
Copyright information: © 2020 Wolters Kluwer Health, Inc. The final authenticated version is available online at https://doi.org/10.1097/RHU.0000000000001268.