Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK.
Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
J Clin Immunol. 2020 Feb;40(2):406-411. doi: 10.1007/s10875-019-00729-x. Epub 2020 Jan 2.
Germline gain-of-function mutations in CARD11 lead to the primary immunodeficiency, B cell expansion with NF-κB, and T cell anergy (BENTA). Herein, we report the case of a girl, presenting at 2 years of age with lymphocytosis and splenomegaly in whom a novel, in-frame, three base pair deletion in CARD11 was identified resulting in the deletion of a single lysine residue (K215del) from the coiled-coil domain. In vitro functional assays demonstrated that this variant leads to a subtle increase in baseline NF-κB signaling and impaired proliferative responses following T cell receptor and mitogenic stimulation. Previously reported immunological defects associated with BENTA appear mild in our patient who is now 6 years of age; a B cell lymphocytosis and susceptibility to upper respiratory tract infections persist; however, she has broad, sustained responses to protein-polysaccharide conjugate vaccines and displays normal proliferative responses to ex vivo T cell stimulation.
CARD11 胚系获得性功能突变导致原发性免疫缺陷、B 细胞扩增伴 NF-κB 和 T 细胞无能（BENTA）。在此，我们报告了一例女孩病例，其在 2 岁时出现淋巴细胞增多和脾肿大，在 CARD11 中发现了一种新的、无框的、三个碱基对缺失，导致卷曲螺旋结构域中单个赖氨酸残基（K215del）缺失。体外功能测定表明，这种变体导致 NF-κB 信号的基线轻微增加，并在 T 细胞受体和有丝分裂原刺激后导致增殖反应受损。先前报道的与 BENTA 相关的免疫学缺陷在我们的患者中表现为轻度，该患者现已 6 岁；B 细胞淋巴细胞增多和对上呼吸道感染的易感性持续存在；然而，她对蛋白多糖结合疫苗有广泛、持续的反应，并表现出对体外 T 细胞刺激的正常增殖反应。
