Elsayed Abdulwahab, von Hardenberg Sandra, Atschekzei Faranaz, Siek Paul, Witte Torsten, Sogkas Georgios, Ringshausen Felix C
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany; Hannover Medical School, Cluster of Excellence RESIST (EXC 2155), Hannover, Germany.
Department of Human Genetics, Hannover Medical School, Hannover, Germany.
Clin Immunol. 2025 Jul;276:110504. doi: 10.1016/j.clim.2025.110504. Epub 2025 Apr 22.
Hemizygous germline loss-of-function variants in DOCK11, the gene encoding the dedicator of cytokinesis 11 (DOCK11) have been recently identified to cause variable immunodeficiency and immune dysregulation. Features of immune dysregulation have been reported in all so far identified male patients with damaging variants in DOCK11, commonly manifesting with autoimmune cytopenias, inflammatory bowel disease, benign lymphoproliferation and systemic inflammation. In this study, we identified a novel variant in DOCK11 (c.3754C > T, p.(Q1252*)), leading to loss of protein expression, in a patient with a history of recurrent pneumonia, bronchiectasis, infection-triggered hyperinflammation and persistent systemic inflammation. Reevaluation of all previously identified patients and the current case, reveals that variants leading to the complete loss of DOCK11 expression and consequently function rather associate with autoinflammation and recurrent pneumonias, while missense variants, primarily associate with autoantibody-related autoimmune features.
编码胞质分裂专用蛋白11（DOCK11）的基因DOCK11中的半合子种系功能丧失变异最近被确定可导致可变免疫缺陷和免疫失调。在所有迄今已确定的携带DOCK11有害变异的男性患者中均报告了免疫失调的特征，通常表现为自身免疫性血细胞减少、炎症性肠病、良性淋巴细胞增殖和全身炎症。在本研究中，我们在一名有复发性肺炎、支气管扩张、感染引发的过度炎症和持续性全身炎症病史的患者中，鉴定出DOCK11中的一个新变异（c.3754C>T，p.(Q1252*)），该变异导致蛋白表达缺失。对所有先前确定的患者和当前病例的重新评估显示，导致DOCK11表达完全丧失并因此导致功能丧失的变异更常与自身炎症和复发性肺炎相关，而错义变异主要与自身抗体相关的自身免疫特征相关。
