Gene defect leads to warts and more

From San Diego, at a meeting of the American Society of Human Genetics

To attract immune cells to infection, the body uses signals called chemokines. Like noses on bloodhounds, chemokine receptors on immune cells sniff for chemical cues, in this case, chemokines in blood.

Researchers have for the first time associated a disease with mutations in a gene for one of these receptors. People with a rare disorder known as WHIM syndrome suffer warts and recurrent bacterial infections. The patients have normal immune cells, but the cells seem to have trouble moving out from their home in bone marrow toward an infection, says George A. Diaz of the Mount Sinai School of Medicine in New York.

For several years, he and his colleagues have worked with five families in which WHIM syndrome is common. Through DNA analyses of affected and unaffected family members, the scientists have now found a gene responsible for the syndrome. Four of the families possess mutations in the gene for a chemokine receptor called CXCR4.

This discovery may explain the odd occurrence of warts in WHIM syndrome. Diaz speculates that the chemokine receptor plays a role in the immune response to wart-causing human papilloma virus.

The genetic finding may also hold a lesson for scientists pursuing new drugs against HIV, the AIDS virus. To get into cells, HIV latches onto a chemokine receptor (SN: 6/22/96, p. 390: Usually, the virus goes for the so-called CCR5 receptor, but some HIV strains latch onto CXCR4. Because people carrying mutations that rob them of CCR5 receptors are healthy, some scientists suspect that anti-HIV drugs that block CCR5 will have few or no side effects. In contrast, the link between WHIM syndrome and the CXCR4 receptor suggests that any drugs targeting this chemokine receptor could have significant side effects, cautions Diaz.