title: Aberrant humoral immune reactivity in DOCK8 deficiency with follicular hyperplasia and nodal plasmacytosis.
abstract: 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.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), Amsterdam, The Netherlands; Emma Children's Hospital, AMC, Amsterdam, The Netherlands. Electronic address: d.j.aandekerk@amc.nl.
authors.forename: Daan J
authors.initials: DJ
authors.lastname: aan de Kerk
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.forename: Machiel H
authors.initials: MH
authors.lastname: Jansen
authors.forename: J Merlijn
authors.initials: JM
authors.lastname: van den Berg
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.forename: Clementine L
authors.initials: CL
authors.lastname: Vermont
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Steven T
authors.initials: ST
authors.lastname: Pals
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D056724:Immunity, Humoral; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D008976:Molluscum Contagiosum / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000906:Antibodies; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors
keywords: Antigen-specificity; DOCK8; HSCT; Hyper-IgE; Memory response; Molluscum contagiosum