vCJD transmission 'risk for all'

One gene type has accounted for virtually all vCJD cases

Everyone could be susceptible to vCJD infection via blood transfusions but their genes could determine how it will affect them, a study suggests.

So far, virtually all cases of vCJD in humans have been in people with one particular genetic profile.

But mouse tests by National CJD Surveillance Unit and Institute for Animal Health scientists suggest those with other gene types are at risk.

The Lancet Neurology said incubation periods could be longer for some.

To date, 161 cases of vCJD (variant Creutzfeld Jakob disease) have been reported in the UK, 18 in France and 12 in the rest of the world - most of those of UK origin.

At present, it is not clear how susceptible people might be to transmission of vCJD through routes such as blood transfusions.

As there is currently no test for the disease, this could potentially mean that someone receives blood or blood products from someone who is carrying vCJD but does not know it.

The researchers, who are based in Edinburgh, focused on differences in a gene which makes the normal version of the rogue "prion" protein involved in vCJD.

The gene encodes for two different types of amino acid - methionine (M) or valine (V).

Amino acids are the building blocks of proteins.

Everyone has two copies (alleles) of the gene, so they can be MM, MV or VV.

Virtually all those who have developed vCJD so far have had the MM genotype, carried by around 40% of the population.

There has only been one exception - an MV patient developed the disease following a blood transfusion.

'Species barrier'

Around 50% of the population are MV, while the rest carry the VV genotype.

The researchers altered mice to have one of the three human genotypes, or a bovine form, before injecting them with brain material from cases with vCJD or the related cattle disease BSE (bovine spongiform encephalopathy).

Post-mortem brain tissue tests were used to see if there were signs of BSE or vCJD.

BSE was transmitted to mice with bovine genes, but not to those with human ones, which the researchers say shows there is a significant "species barrier" which could explain why relatively few people have been infected and developed vCJD.

However, vCJD was successfully transmitted to mice with all three human genotypes, but behaved differently in each.

Transmission occurred least easily in the 16 VV mice compared to the 16 with the MV gene pattern and the 17 with MM.

However, most of the MV animals did not develop clinical signs of vCJD during their short lifetime compared to those with MM, most of whom did.

Only one mouse with VV showed signs it had contracted the disease, though it had no clinical symptoms.

'Partly reassuring'

Writing in Lancet Neurology, the researchers led by Jean Manson at the Institute for Animal Health, said: "Our findings raise concerns relevant to the possibility of secondary transmission of vCJD through blood transfusion, blood products or contaminated surgical instruments."

They added: "For human-to-human vCJD infection it should be assumed that all genotype individuals - not just MM - can be infected, that long incubation times can occur, and that a significant level of subclinical [symptom-free] disease might be present in the population."

In an editorial in the journal, Dr Corinne Lasmezas, of the Department of Infectology at Scripps Research Institute in Florida, agreed with the researchers' conclusions.

She added: "Some MV individuals, and a very small number of VV individuals could become asymptomatic carriers.

"In this regard, it is unfortunate that only 10% of the population carries two V alleles, reducing the impact of this partly reassuring finding."