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

Clin Immunol. 2013 Oct;149(1):25-31. doi: 10.1016/j.clim.2013.06.002. Epub 2013 Jun 19.

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.

Keywords: Antigen-specificity; DOCK8; HSCT; Hyper-IgE; Memory response; Molluscum contagiosum.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antibodies / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cell Proliferation
  • Female
  • Guanine Nucleotide Exchange Factors / deficiency*
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / immunology
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Hyperplasia / genetics
  • Hyperplasia / immunology
  • Hyperplasia / pathology
  • Hyperplasia / therapy
  • Immunity, Humoral
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / pathology
  • Immunologic Deficiency Syndromes / therapy
  • Lymph Nodes / pathology
  • Lymphocyte Count
  • Molluscum Contagiosum / genetics
  • Molluscum Contagiosum / immunology*
  • Molluscum Contagiosum / pathology
  • Molluscum Contagiosum / therapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • Antibodies
  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors