Prion proof? A common genetic factor may give protection against the human form of mad cow disease.

Immune System Gene Linked to 'Mad Cow' Risk

Researchers have pinned down a genetic variation that may help protect against variant Creutzfeldt-Jakob disease (vCJD)--the fatal neurodegenerative disease linked to eating cattle infected with "mad cow disease." The new finding--the second genetic factor thought to influence susceptibility--may help identify high-risk individuals and provide some clues about this incurable malady.

Most researchers believe that vCJD is caused at least partly by aberrant proteins called prions, misfolded versions of a normal cellular protein called PrP, which are ingested in contaminated meat. Genetics clearly play a role in susceptibility to the disease: So far, all of the more than 100 people diagnosed with vCJD in the United Kingdom have the same variation of the gene that codes for PrP. At least seven other genes affect susceptibility to prions in mice.

Now, a new genetic factor has been identified in humans that influences susceptibility to vCJD: A team led by neurologist John Collinge at University College London reports in the 15 November issue of Nature that more than 80% of vCJD victims lack a version of an immune system protein called human leukocyte antigen (HLA), which helps recognize infectious agents. The HLA proteins vary depending on genetic makeup. One form, called HLA-DQ7, was found in 35.5% of 197 normal control individuals. But this form turned up in only 12% of 50 vCJD patients studied. The researchers conclude that DQ7 somehow protects against vCJD, perhaps by helping the immune system fight off prions.

It could also play another role: Recent studies suggest that prions travel from the gut to the brain through immune system organs such as the lymph nodes. If HLAs are involved in this transport, for example by binding to the prions--and if DQ7 is less efficient in this role--this could also explain the results.

The implication of an immune system gene makes perfect sense to neuropathologist Adriano Aguzzi of the University of Zürich. "It hardly comes as a surprise," he says, pointing to the importance of the lymphoid organs in the etiology of vCJD. But Aguzzi, as well as the paper's authors, caution that DQ7 may play only an indirect role: It could just be closely linked to other genes that are more directly controlling susceptibility to vCJD.

Related sites

U.K. Creutzfeldt-Jakob disease surveillance
Spongiform Encephalopathy Advisory Committee
Page about prion diseases hosted by the World Health Organization