Low levels of key antibodies may lead to severe disease, study suggests
Reported September 17, 2009
TORONTO Australian researchers may have uncovered a clue as to why some people who catch swine flu suffer life-threatening illness.
And if they are right, there is an existing weapon in the treatment arsenal that could help reduce the pandemic death toll. The group found that pregnant women who became severely ill with the new H1N1 virus had low levels of a particular antibody that is known to fight off viruses and help the body respond to vaccine.
Moderately ill women were much less likely to have significantly suppressed levels of the antibody, the researchers reported. “We all believe we may have stumbled onto something very interesting,” said Dr. Lindsay Grayson, director of infectious disease at Austin Health, a network of three hospitals in Melbourne.
“To our knowledge it’s the first time that a correlation or an association is being noted between severe influenza of any sort and a subtle but potentially important immune deficiency.”
The team made the discovery when Grayson’s colleague, Dr. Claire Gordon, ordered a test that looked at antibody levels – not just by class, but looking at individual subtypes within those classes. The call was made in the case of a very sick patient whose decline was particularly rapid, and the team was debating whether immune globulin – a blood product containing antibodies harvested from donated blood – might help.
The testing showed the patient had low levels of an antibody called IgG2, which Grayson admitted came as a surprise. They started ordering tests on all their swine flu patients in ICU.
“What we found was almost everyone, all the patients who needed ICU were IgG2 deficient,” he said in an interview from San Francisco, where the data were presented at ICAAC, the annual meeting of the American Society for Microbiology. Severe cases had IgG2 levels that were about one-third of those detected in people who were moderately ill.
While the work was only done in pregnant women, Grayson and others said it would be useful to look to see if this deficiency might explain why a small subset of swine flu cases become gravely ill while most people only suffer through a bout of the flu.
It’s known that between two and 20 per cent of people have some antibody deficiency, he said, though not all of those people would be IgG2 deficient.
Three of four critically ill patients treated with immune globulin survived, defying predictions of those caring for them.
Dr. Donald Low, chief microbiologist at Toronto’s Mount Sinai, said the findings are exciting, if preliminary, and might explain why aboriginals seem to be at greater risk of developing severe disease if they contract swine flu. He suggested the hypothesis should be studied further.
“It would be a fishing expedition, but obviously worthwhile.” “I think the bottom line is that this is obviously something that has to be looked into.
And it may have therapeutic implication. … It could be a marker for women at higher risk if they get infected to get more severe disease.”
But Dr. Anand Kumar, an intensive care specialist from Winnipeg who treated a lot of severely ill swine flu patients in the spring and early summer, was not as optimistic.
“The results are just what I’d expect in any group of critically ill,” he said by email. Kumar, who is also an infectious diseases specialist, said it is not uncommon for all antibody levels to drop with critical illness and the more severe the sickness, the steeper the drop.
But he does think the notion of treating pandemic flu patients with antibodies harvested from other people makes sense, though he believes the immune globulin should be from people who’ve recovered from swine flu and have antibodies specific to the virus.
Grayson admitted they can’t say at this point whether there is a cause-and-effect relationship at work here, meaning low IgG2 levels in the patients predisposed them to suffering from more severe disease once they caught the virus.
But he doesn’t believe the reverse is at play, that the infection caused the low IgG2 levels.
“We don’t think that influenza is causing this deficiency. We think that instead the influenza is picking out those people who have the deficiency,” he said.
The numbers are admittedly small and will require further study, likely in the Northern Hemisphere. Swine flu rates are dropping in Melbourne, Grayson said.
Still, 16 of 19 severely ill patients had very low IgG2 levels, compared to three of 20 with moderate illness.
The team looked at healthy pregnant women and found that about 60 per cent of them were mildly deficient in IgG2 levels, which leads them to believe this may be one of the immune system changes that occurs to allow a pregnant woman to carry a foreign body – a fetus – without rejecting it. But Grayson said the group needs to follow women after they deliver to see if their IgG2 levels rise to normal levels.
Grayson said while the group’s work hasn’t proven their hypothesis, Northern Hemisphere doctors caring for the sickest of swine flu patients in the weeks and months to come should consider checking IgG2 levels and using immune globulin, which is often given to people seriously ill with some bacterial infections.
“In many ways, this is applying a general principle that we apply to bacteria diseases to now say well, ‘Gee, we’ve made this interesting observation. This might work for influenza,”‘ he said.
Follow Canadian Press Medical Writer Helen Branswell’s flu updates on Twitter at CP-Branswell
Source : The Canadian Press
