George A Diaz, MD, PhD

WHIM syndrome is a rare immunodeficiency causing hypogammaglobulinemia, neutropenia and predisposition to warts. Affected individuals have been found to carry truncating mutations in the tail domain of the CXCR4 chemokine receptor. The pathogenesis of the disease appears to involve both a neutrophil trafficking defect as well as a defect in lymphocyte function. While the nature of the susceptibility to HPV is poorly understood, additional study should provide insight into the role of the receptor in the host response to infection by HPV, a cause of significant human morbidity. Studies currently underway include the characterization of a mouse model expressing mutant CXCR4 in selected hematopoietic tissues, genetic studies with functional candidate genes in families with the WHIM syndrome phenotype without mutations in CXCR4, and biochemical characterization of the signaling perturbations in disease cells carrying CXCR4 truncations.