WHIM syndrome: Immunopathogenesis, treatment and cure strategies

Immunol Rev. 2019 Jan;287(1):91-102. doi: 10.1111/imr.12719.

Abstract

WHIM syndrome is a rare, autosomal dominant immunodeficiency which is named for the four key manifestations: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. It results from heterozygous gain-of-function mutations in the chemokine receptor CXCR4 which is widely expressed on leukocytes and has profound influences on immune system homeostasis and organogenesis. New treatments for the disease using drugs to reduce CXCR4 function are excellent examples of precision medicine. Since CXCR4 and its ligand CXCL12 play an important role in a variety of infectious, inflammatory, autoimmune, and malignant diseases, the study of WHIM syndrome provides important insights into both the physiologic and disease roles of these molecules.

Keywords: bone marrow transplantation; gene therapy; human papillomavirus (HPV); plerixafor; primary immunodeficiency.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Agammaglobulinemia
  • Animals
  • Humans
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / therapy
  • Infections
  • Leukopenia
  • Molecular Targeted Therapy
  • Papillomaviridae / physiology*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / therapy
  • Precision Medicine
  • Primary Immunodeficiency Diseases
  • Receptors, CXCR4 / genetics*
  • Warts / genetics
  • Warts / immunology*
  • Warts / therapy

Substances

  • CXCR4 protein, human
  • Receptors, CXCR4

Supplementary concepts

  • WHIM syndrome