A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment. Issue 8 (December 2021)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal of clinical rheumatology. Volume 27:Issue 8(2021)
• Page Start: e583
• Page End: e587
• Publication Date: 2021-12
• Subjects: anakinra -- anemia -- autoimmunity -- autoinflammation -- immunodeficiency -- lung disease -- mycophenolate; Rheumatism -- Periodicals; Rheumatology -- Periodicals; Musculoskeletal system -- Diseases -- Periodicals; Musculoskeletal Diseases -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Rhumatologie -- Périodiques; Appareil locomoteur -- Maladies -- Périodiques; Musculoskeletal system -- Diseases; Rheumatism; Rheumatology; Periodicals; 616.723005
• DOI: 10.1097/RHU.0000000000001268
• Languages: English
• ISSNs: 1076-1608

Abstract

Abstract : Supplemental digital content is available in the text. 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.