|
|
A family with A20 haploinsufficiency presenting with novel clinical manifestations and challenges for treatment |
|---|---|
| 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: | open |
| Online Access: | PDF Full Text (PDF, 0.5 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2020100778342 |
| Language: | English |
| Published: |
Wolters Kluwer,
2021
|
| Publish Date: | 2021-01-21 |
| Description: |
AbstractBackground: 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. see all
|
| Series: |
JCR. Journal of clinical rheumatology |
| ISSN: | 1076-1608 |
| ISSN-E: | 1536-7355 |
| ISSN-L: | 1076-1608 |
| Volume: | 27 |
| Issue: | 8 |
| Pages: | e583 - e587 |
| 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. |