Department of Experimental Immunology, Academic Medical Center (AMC), Amsterdam, The Netherlands; Emma Children's Hospital, AMC, Amsterdam, The Netherlands.
Clin Immunol. 2013 Oct;149(1):25-31. doi: 10.1016/j.clim.2013.06.002. Epub 2013 Jun 19.
Mutations in the DOCK8 gene define the most common form of autosomal-recessive Hyper-IgE-syndrome (AR-HIES/OMIM#243700). In a patient with extensive molluscum contagiosum lesions, a homozygous DOCK8 gene deletion was demonstrated. In-vivo 18-FDG uptake showed multiple non-enlarged lymph nodes without uptake in the spleen. Lymph node biopsies for subsequent immunohistochemistry showed clear differences with the mouse model of DOCK8 deficiency in which these mice show no GCs. Unexpectedly, the patient's lymph nodes demonstrated lymphocyte polyclonality, follicular hyperplasia and an unusual IgE(+) plasma cell expansion. In contrast, the proliferative capacity of circulating B-cells was almost absent with little in-vitro Ig production or plasmablast formation. Also the T-cell proliferation indicated a partial defect. Hematopoietic stem cell transplantation (HSCT) was performed resulting in the disappearance of the molluscum contagiosum lesions. In sum, DOCK8 deficiency results in defective antibody responses and undirected plasma cell expansion in the lymph nodes, as part of a combined immunodeficiency cured by HSCT.
DOCK8 基因突变定义了最常见的常染色体隐性遗传高免疫球蛋白 E 综合征（AR-HIES/OMIM#243700）。在一名患有广泛传染性软疣病变的患者中，证实存在 DOCK8 基因纯合缺失。体内 18-FDG 摄取显示多个非肿大的淋巴结，脾脏无摄取。随后进行的免疫组化淋巴结活检显示与 DOCK8 缺陷的小鼠模型存在明显差异，这些小鼠没有 GC。出乎意料的是，患者的淋巴结显示淋巴细胞多克隆性、滤泡增生和异常的 IgE(+)浆细胞扩增。相比之下，循环 B 细胞的增殖能力几乎缺失，体外 Ig 产生或浆母细胞形成很少。此外，T 细胞增殖也表明存在部分缺陷。进行了造血干细胞移植（HSCT），导致传染性软疣病变消失。总之，DOCK8 缺乏导致淋巴结中抗体反应缺陷和未定向浆细胞扩增，这是一种联合免疫缺陷，可通过 HSCT 治愈。
