Tuesday 28 April 2009

Storm: Why PIDers may be better off...

A couple of people asked why people with PIDs might be more likely to survive a 'flu pandemic.

Immunocompetent people respond to infection in a numbers of ways simultaneously, one of which is the complement system. However, the complement system can also be activated by the actions of antibodies: this was graphically demonstrated in the TGN1412 tragedy in which the monoclonal (ie: identical) antibody caused the complement system to over-react by causing a "cytokine storm".

The complement system is activated by a cascade of proteins (cytokines, a type of signalling molecule), each of which activates the next protein in the chain. In fact, each parent protein in the chain activates many of their child proteins.

When this cascade isn't regulated (eg. by feedback turning off the parent proteins), it becomes an uncontrolled "storm", resulting in massive, rapid inflammation, oedema (water swelling), vasoconstriction (reduced blood flow) and shock.

The hypothesis is that this type of reaction causes many of the serious complications in healthy, young people. This is the pattern of fatality that was seen in the 1918 Spanish Flu pandemic, in which working-age, healthy men had higher mortality rates than any other group.

However, there may be other explanations as to why that group had higher mortality rates - not least of which is that this is the group perhaps most likely to mix together and most likely to attend work when unwell. So it's far from clear that the hypothesis is proven, and even then it might be just part of the explanation.

The logical extension of the hypothesis is that if you have certain immune problems, this might reduce your susceptibility to this type of reaction, which would confer a survival advantage on those of us with those immune problems. However, it's difficult to say at this point in time whether that is relevant to the current outbreak of swine flu.

In short, we may have an advantage but it's far from clear. If we do, I think we'll all be relieved that, for one, the PID is giving something back.

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