A novel de novo activating mutation in STAT3 identified in a patient with common variable immunodeficiency (CVID)

作者：Russell Mark A^*; Pigors Manuela; Houssen Maha E; Manson Ania; Kelsell David; Longhurst Hilary; Morgan Noel G

来源：Clinical Immunology, 2018, 187: 132-136.

DOI：10.1016/j.clim.2017.11.007

• Common variable immunodeficiency CVID
• Hypogammaglobulinemia
• STAT3
• Whole exome Sequencing

Common variable immunodeficiency (CVID) is characterised by repeated infection associated with primary acquired hypogammaglobulinemia. CVID frequently has a complex aetiology but, in certain cases, it has a monogenic cause. Recently, variants within the gene encoding the transcription factor STAB were implicated in monogenic MD. Here, we describe a patient presenting with symptoms synonymous with CVID, who displayed reduced levels of IgG and IgA, repeated viral infections and multiple additional co-morbidities. Whole-exome sequencing revealed a de novo novel missense mutation in the coiled-coil domain of STAT3 (c.870A>T; p.K290N). Accordingly, the K290N variant of STAT3 was generated, and a STAT3 responsive dual-luciferase reporter assay revealed that the variant strongly enhances STAT3 transcriptional activity both under basal and stimulated (with IL-6) conditions. Overall, these data complement earlier studies in which CVID-associated STAB mutations are predicted to enhance transcriptional activity, suggesting that such patients may respond favourably to IL-6 receptor antagonists (e.g. tocilizumab).

• 出版日期2018-2