The WHIM Syndrome
The WHIM syndrome is a rare immunodeficiency characterized by Warts, Hypogammaglobulinemia, recurrent respiratory bacterial Infections, and Myelokathexis. Early studies identified that neutrophils in WHIM patients are retained in the bone marrow; severe peripheral neutropenia and lymphocytopenia were also observed. Infections of the upper respiratory tracts and lesions due to human papillomavirus (HPV) are common. Association with tetralogy of Fallot and Waldenström macroglobulinemia was described. The WHIM syndrome is mostly caused by heterozygous mutations on chromosome 2q21 that truncate the C-terminal tail of the chemokine receptor CXCR4, the cognate receptor to chemokine CXCL12. The CXCR4-CXCL12 interaction plays a key role in the recruitment of hematopoietic progenitors into the bone marrow and in the regulation of lymphocyte trafficking within secondary lymphoid organs. Current recommendations for WHIM syndrome include vaccinations and antibiotics to prevent infections, as well as usage of G-CSF and as an immune cell-mobilizing agent to combat myelokathexis. Intravenous immunoglobulin (IVIG) injections can be used to treat hypogammaglobulinemia.
Given the ability of AMD3100 to inhibit CXCR4 signaling, it has been suggested as a therapy for myelokathexis in WHIM syndrome.
KeywordsWHIM CXCR4 G-CSF HPV Waldenström CXCL12
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