Unexpected developments in immune organs in WHIM syndrome

摘要

In this issue of Blood, Balabanian and colleagues describe a mouse model of WHIM syndrome, a combined myeloid and lymphoid immunodeficiency disorder. The results provide a high-definition histopathologic picture of the effects of WHIM mutation CXCR4~1013 on immune organs and suggest complex, unexpected defects in both leukocyte trafficking and development. Consider a patient with recurrent bacterial sino-pulmonary infections since early childhood. During infection the absolute neu-trophil count (ANC) is elevated but falls below normal with recovery. Immunoglobulin levels and circulating B cells are also decreased; CD4~+ T lymphocytes are as low as in AIDS. In fact, almost all circulating leukocyte subsets are low. Yet classic opportunistic infections do not occur, bacterial infections usually do not become life-threatening, and the main problematic virus is human papillomavirus (HPV), which causes large numbers of skin and ano-genital warts. The mother, brother, and 2 of 3 children of this patient have a similar condition.