Re: most wanted jams

[Guest guest]

* Dubois' Lupus Erythematosus

I hear this is the authoritative book on SLE. Haven't seen it yet.

* The Decade of Autoimmunity

I was attracted when I read the editor's introduction via my Amazon

account. He wrote with conservatism on the proof of autoimmune

pathogenesis. But his intro is pretty damn short. The rest of the book

is papers on mixed topics by different authors. They're a nice mix,

addressing many different diseases. Book's about 10 years old though.

[Guest guest]

Currently on deck:

Susceptibility to infectious diseases : the importance of host genetics.

Bellamy, ( )

Infectious diseases in primates : behavior, ecology and evolution.

Nunn, L.

Evolution in health and disease.

Stearns, S. C. ( C.), 1946-

> * Infectious disease and host-pathogen evolution

> Dronamraju, Krishna R.

>

> Haven't read it yet, but it exists. It's blue in color.

This book was great. The Cochran and Cochran chapter is very clear and

gives a quantitative evolutionary argument for infection (persistent

or transient) as the primary cause of diabetes mellitus I and II.

I no longer totally subscribe to this line of thinking. I do think all

longstanding diseases with a high fitness load are probably caused by

infection, in general - but humans have changed so rapidly in their

behavior and selection pressures, that I think it might be a little

shaky to apply this to humans. Furthermore, I am applying an unusual

meaning to " caused by infection. " Look at sickle cell disease. It's

caused by a homozygosity for the hemoglobin S allele, but the

preservation of that allele in the population is caused by the

heterozygote advantage against malaria (at least, so they say; but on

the other hand it looks like hemoglobin S may *not* be waning in

non-malarious areas:

http://muse.jhu.edu/journals/human_biology/v073/73.4hoff.pdf

Anyway, the point is, *Plasmodium* gave you sickle cell disease, but

you never had to come within 1000 miles of one. Something similar

could be possible in the immune diseases, when it comes to genes like

CTLA4, which is involved in lymphocyte activation and has an common

allele that's overrepresented in a number of immune diagnoses. When a

mammal population faces heavy selection from a novel infectious

challenge, alleles lowering the bar for T lymphocyte activation may

proliferate, even if they increase the risk of autoimmunity or

inappropriate attacks on persistent systemic commensal microbes. At

time points where the mammal population has not faced novel infections

recently - and has evolved more refined defenses against the pathogens

it has long been adapting (defenses that are better because they don't

risk self-harm) - these sort of T lymphocyte hyperactivity alleles

will decline in frequency. But, since microbes evolve much faster, it

seems at least possible that mammals populations might hang on more or

less permanently to various sorts of alleles favoring mild T cell

hyperactivity.

One would need quantitative expertise (in evolution rates and pathogen

host-jumping) to fully complete this argument. But in short,

hemoglobin S and the cystic fibrosis mutation, which may well be

" crude " alleles favoring immunity to important pathogens, are highly

suggestive. Why wouldn't there be other " crude " alleles out there that

confer fitness to blighted host populations, at a cost - but are not

so terribly blunt as to produce a highly-penetrant phenotype as

hemoglobin S and CFTR do. The most impressive investigation would be

to round up *all* alleles that are like the immune-disease CTLA4

allele, and see if typing subjects for *all* of them at once can give

high predictive power as to lifetime risk of immune disease (the CTLA4

allele alone gives almost no predictive power, having a frequency

around 0.45 in normals and 0.55 in certain immune diseases, or

something like that; yet, since the studies were large, the

statistical significance apparantly is there, according to the Parham

immunology textbook). I'm not aware, though, of any others like CTLA4

which seem to cut across a *variety* of *common* diagnoses.

[Guest guest]

> * Dubois' Lupus Erythematosus

>

> I hear this is the authoritative book on SLE. Haven't seen it yet.

I have the latest edition from the libe. It's been very rewarding so

far... very detailed... what I been looking for. Especially

interesting is that lupus can be installed in normal inbred mice using

just 2 of the genes from the NZB/NZW inbred mouse model complex. So

these things are not always intractably polygenic.

> Susceptibility to infectious diseases : the importance of host genetics.

Bellamy, ( )

This has a really sweet discussion of MHC determination of infection.

The article on NRAMP1 polymorphisms is also cool.

> Infectious diseases in primates : behavior, ecology and evolution.

Nunn, L.

I skimmed a lot of this. Much of it wasn't so interesting to me.

Mainly what I learned is that it doesn't look like primates have a lot

of hypervirulent epidemic diseases. Presumably because of their

smaller and less intensive contact networks, whereas (some) humans

have been living densely since the advent of agriculture about 10,000

years ago. For us on the other hand, hypervirulent epidemic disease is

one of the monster changes in our recent selection/evolution, along

with intelligence and bipedalism.

Wild primates do have (at least): malarias; tons of gut and systemic

worms; some viruses; an apparant treponemosis; occasional but not

really endemic bovis TB (possibly an " artifact " of human civilization;

some monkeys may eat M bovis from dead domestic cows etc).