TY - JOUR
T1 - Aberrant humoral immune reactivity in DOCK8 deficiency with follicular hyperplasia and nodal plasmacytosis
AU - Aan de Kerk, Daan J.
AU - van Leeuwen, Ester M. M.
AU - Jansen, Machiel H.
AU - van den Berg, J. Merlijn
AU - Alders, Marielle
AU - Vermont, Clementine L.
AU - van Lier, René A. W.
AU - Pals, Steven T.
AU - Kuijpers, Taco W.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.clim.2013.06.002
DO - https://doi.org/10.1016/j.clim.2013.06.002
M3 - Article
C2 - 23891736
SN - 1521-6616
VL - 149
SP - 25
EP - 31
JO - Clinical immunology (Orlando, Fla.)
JF - Clinical immunology (Orlando, Fla.)
IS - 1
ER -