Aberrant humoral immune reactivity in DOCK8 deficiency with follicular hyperplasia and nodal plasmacytosis

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• 作者：Daan J. aan de Kerk ; Ester M.M. van Leeuwen ; Machiel H. Jansen ; J. Merlijn van den Berg ; Marielle Alders ; Clementine L. Vermont ; Ren¨¦ A.W. van Lier ; Steven T. Pals ; Taco W. Kuijpers
• 关键词：Hyper-IgE ; DOCK8 ; Molluscum contagiosum ; HSCT ; Antigen-specificity ; Memory response
• 刊名：Clinical Immunology
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：149
• 期：1
• 页码：25-31
• 全文大小：1100 K

文摘

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.