A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment

• Published in: Journal of clinical rheumatology
• Main Authors: 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 R J
• Format: Journal Article
• Language: English
• Published: United States 01.12.2021
• ISSN: 1536-7355
• DOI: 10.1097/RHU.0000000000001268

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. 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. 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. 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.