Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu.
Department of Clinical Genetics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu.
J Clin Rheumatol. 2021 Dec 1;27(8):e583-e587. 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.
肿瘤坏死因子α诱导蛋白 3 基因（TNFAIP3，也称为 A20）杂合不足（HA20）可导致自身炎症和自身免疫。我们最近表明，A20 中的 p.(Lys91*)突变会破坏核因子 κB 信号转导，损害 A20 的蛋白-蛋白相互作用，并导致炎性体激活。
我们现在描述了一个具有 HA20 p.(Lys91*)突变的家族的临床表现和药物反应，与我们之前报告的多样化的免疫学和功能发现一致。
我们首次报告了由 HA20 引起的炎性体介导的自身炎症性肺反应可以用白细胞介素 1 拮抗剂 anakinra 治疗。我们还描述了用霉酚酸酯成功治疗与 HA20 相关的严重贫血。此外，还发现 HA20 p.(Lys91*)与自身免疫性甲状腺疾病、幼年特发性关节炎、银屑病、肝脏疾病和免疫缺陷相关，表现为特定抗体缺乏和生殖器乳头瘤病。
我们得出结论，HA20 可能导致炎症、免疫缺陷和自身免疫的结合。该病症可能表现出多变且不可预测的症状，对治疗反应不典型。
