How Swine Flu Killed the Healthy (Science)

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How Swine Flu Killed the Healthy

The H1N1 pandemic virus that took the world by storm in 2009 may have had an

unexpected accomplice. Some of the thousands who died may have been victims of

their own immune systems, suggests a paper appearing in Nature Medicine today.

The study provides a possible answer to one of the most baffling questions since

the virus appeared in the spring of last year: Why did the virus cause most

damage in 20- to 50-year-olds—who are generally the healthiest—while sparing the

very young and the very old?

Influenza pandemics occur when a totally new strain of the virus emerges,

against which nobody's immune system is fully prepared; that's why both the

healthy and the weak are vulnerable. But that doesn't explain why senior

citizens, with generally weaker immune systems, and young children, with no

immunity to influenza whatsoever, tended to get cases of H1N1 that were milder

than their healthier counterparts. " In a middle-aged population, we saw a lot of

people getting very, very ill, " says pediatrician Polack of Vanderbilt

University in Nashville, Tennessee.

The reason, according to Polack, is that their immune systems' programming

backfired. After looking at lung samples from 75 young and middle-aged adult

victims of the 2009 pandemic, they found an uncanny amount of a protein called

C4d, a molecule that normally binds to antibodies to form virus-fighting immune

complexes.

When antibodies fight a virus under normal conditions, Polack says, they call in

C4d, a compound that can destroy viruses. In the case of flu, most people had

antibodies to seasonally circulating influenza strains, but these antibodies

were a poor match to the pandemic virus. Although they recognized the virus and

latched on to it, they weren't able to stop it from replicating, says Polack.

When the antibodies and the C4d formed the immune complexes, Polack speculates

that the system spiraled out of control. Instead of punching holes in the

viruses, the immune complexes punched holes in the victims' veins and flooded

their lungs with water and plasma. " The immune system gets fooled into

activating this particular immune defense, and it causes harm, " says Niranjan

Bhat, an infectious disease physician at s Hopkins Children's Center in

Baltimore, land, who was not part of the research.

This was less likely to happen in young children and infants, with few or no

antibodies against seasonal flu strains, says Polack. And elderly people had

antibodies to the H1N1 strain that circulated in the United States until 1957—a

descendant of the Spanish flu pandemic of 1918—which are known to be a much

better match to the 2009 H1N1 strain; so the flood of C4d generally didn't occur

in them. When the team looked at lung samples from victims of the seasonal flu,

they found only trace amounts of C4d, which seemed to confirm their suspicions.

Not everyone is convinced. " There's no doubt that those immune complexes are

there, " says virologist Ron Fouchier of the Erasmus Medical Center in Rotterdam,

the Netherlands. " The question is, are those antibody complexes there because

there's another problem, or are those antibodies there causing the problem? "

But epidemiologist Reichert of the Entropy Research Institute in Lincoln,

Massachusetts, finds Polack's hypothesis completely plausible. There's not much

that could cause this kind of lung damage except an invasion of T lymphocytes

(the immune system's " warrior cells " ), he says, and Polack found no evidence of

that. The immune system's overreaction, says Reichert, is " kind of a last-ditch

way of handling something. ... If we can't identify you specifically enough, but

we know there's a lot of you, we're just going to blow the whole damn place up. "

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