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

Timo Hautala, Paula Vähäsalo, Outi Kuismin, Salla Keskitalo, Kristiina Rajamäki, Antti Väänänen, Marja Simojoki, Marjaana Säily, Ilpo Pelkonen, Heikki Tokola, Markus Mäkinen, Riitta Kaarteenaho, Airi Jartti, Nina Hautala, Saara Kantola, Päivi Jackson, Virpi Glumoff, Janna Saarela, Markku Varjosalo, Kari K. EklundMikko Seppänen

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

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.
Alkuperäiskielienglanti
LehtiJournal of Clinical Rheumatology
Vuosikerta27
Numero8
SivutE583-E587
Sivumäärä5
ISSN1076-1608
DOI - pysyväislinkit
TilaJulkaistu - jouluk. 2021
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3121 Yleislääketiede, sisätaudit ja muut kliiniset lääketieteet

Siteeraa tätä