A family with A20 haploinsufficiency presenting with novel clinical manifestations and challenges for treatment
Hautala, Timo; Vähäsalo, Paula; Kuismin, Outi; Keskitalo, Salla; Rajamäki, Kristiina; Väänänen, Antti; Simojoki, Marja; Säily, Marjaana; Pelkonen, Ilpo; Tokola, Heikki; Mäkinen, Markus; Kaarteenaho, Riitta; Jartti, Airi; Hautala, Nina; Kantola, Saara; Jackson, Päivi; Glumoff, Virpi; Saarela, Janna; Varjosalo, Markku; Eklund, Kari K; Seppänen, Mikko RJ (2020-01-21)
Hautala, T., Vähäsalo, P., Kuismin, O., Keskitalo, S., Rajamäki, K., Väänänen, A., Simojoki, M., Säily, M., Pelkonen, I., Tokola, H., Mäkinen, M., Kaarteenaho, R., Jartti, A., Hautala, N., Kantola, S., Jackson, P., Glumoff, V., Saarela, J., Varjosalo, M., … Seppänen, M. R. J. (2021). A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment. JCR: Journal of Clinical Rheumatology 27(8), e583–e587. https://doi.org/10.1097/rhu.0000000000001268
© 2020 Wolters Kluwer Health, Inc. The final authenticated version is available online at https://doi.org/10.1097/RHU.0000000000001268.
https://rightsstatements.org/vocab/InC/1.0/
https://urn.fi/URN:NBN:fi-fe2020100778342
Tiivistelmä
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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