The danger of "Danger"

Mike Clark mrc7 at cam.ac.uk
Tue Jun 15 06:26:33 EST 1999

In article <37657605.484D at nds.ox.ac.uk>, Derek Gray
<URL:mailto:derek.gray at nds.ox.ac.uk> wrote:
> Mike Clark wrote:
> > It is quite clear that most autoimmune conditions are under polygenic
> > control. 
> Hey, I go away for 3 weeks and all the interesting discussion on Danger
> has been and gone. Just to try and rekindle interest from the dying
> embers, Are you sure about the polygenic argument for autoimmune
> diseases Mike?  I went to a recent talk on cytokine polymorphisms in
> malaria, and was struck by how these various cytokine polymorphisms
> change the phenotype of malaria dramatically (eg from blackwater fever
> to cerebral malaria, to chronic relapsing forms). It struck me that if
> you looked at malaria without knowing the underlying cause it would look
> for all the world like a polygenic disease, yet we know that there is
> only one underlying cause: the malaria parasite.
> Derek Gray

I see what you are saying but surely even in your example above the disease
malaria or more specifically the particular pathology resulting from a
malarial parasite infection is under polygenic control. Clearly the
parasite is required to trigger the pathology but the polymorphisms dictate
to some extent the nature of the pathology.

It is possible to argue almost the mirror example of yours above. Thus in
the NOD mouse it can be argued that IDDM is a result of a lack of
infection. ie infection cures the autoimmune disease! However I wouldn't
argue that there is only one underlying cause to IDDM, 'a lack of

Mike Clark,                        <URL:http://www.path.cam.ac.uk/~mrc7/>
 o/ \\    //            ||  ,_ o   M.R. Clark, PhD. Division of Immunology
<\__,\\  //   __o       || /  /\,  Cambridge University, Dept. Pathology
 ">    ||   _`\<,_    //  \\ \> |  Tennis Court Rd., Cambridge CB2 1QP
  `    ||  (_)/ (_)  //    \\ \_   Tel.+44 1223 333705  Fax.+44 1223 333875

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