Re:- What you think...

[Guest guest]

I for one am interested in what you think.

SInce in my own experience (life-time really) I have grappled with

the auto autoimmunity throries (as linked to suseptibility by tissue

type- or genetics- flaws or otherwise) versus chronic problems

becuase of shronic pathogen load - I have come to think that latter

is the cause of ALOT of diagnosed autoimmune disease becuase of the

resultant HYPERSENSITIVITY of the immune system being constantly

stimulated.

Personally- after being around animals my entire life- I don't think

thrie immune sytems are any different than humans- it's just most

bugs are SPECIES specific - and beleive me - ther are alot of animals

that don't feel well- we just don't norice- or don't care.

In my own case (remember - spenic function is in question with me)

there is no doubt my 'autoimmune dx's' were because of pathogen

burden the immune system couldn't handle.

But host and pathogens DO evolve together - where it's a single life-

time or many... and really- looking at history- the hosts don't

really have the upper hand- and never have..

I think it's just more complicated than Docs want it to be- OH-

you're tissue type Blah Blah - so you're going to get Blah Blah - and

we can't cure it but we have some drugs for you to take the rest of

your life that MAY make you feel even worse (but you'll be ALIVE -

abiet not kicking)...

I RATHER see Western Docs/researchers devise tests to look at the

specific anomolies in individuals (or groups) immune systems as the

catalyst to devise INDIVIDUAL plans of therapy to improve quality of

life- ID the pathogens and them target them in an intelligent way..

But alas- I think mainstream medicine just isn't geared that way.

Chinese medicine- or the ancient ways are more geared to balance-

strong immunity - less stress, etc. they're just not into the drug

scene the way Western Medicine is.

Well I'm blathering...

I'm interested to hear your thoughts now - now that you

understand the immune system better than you did 2 years ago.

Barb

> * 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,

>

[Guest guest]

Barb

just chiming in with a converstaion I had with a school buddy, whom I

found out recently has hep C from tattoos. We venture out

occasionally and he was just a bundle of energy getting up after 3

hours sleep frequently and working his butt off all day.Now the doc

looking after him has started him on interferon therapy and all that

goes with our ilness he's developed...Basically when your host

bacteria are woken they will make your skin burn-fill you full of

toxins- give you fatigue-and several other things he mentioned which

I explained to him- 'NOW WELCOME TO MY CLUB' and most importnatly see

if anyone believes what your going thru, or EVEN CARES!!!So from

fantastic to fatigue whenever your putting your host bacteria thru

the ringer..the way I see it with him is you don't need a pathogen

your oppurtunists will nail your ass...

tony

> >

>

[Guest guest]

Well, the best way to show that something (an antibody, a virus,

anything) is pathogenic, is to transfer it to a healthy animal. That

worked well for the highly virulent microbial pathogens studied in the

1870s and after.

With autoimmunity, it's not so easy to do a transfer. You usually

can't transfer into people for ethical reasons (though I think some of

the early guys studying anti-platelet antibodies did perform transfers

into themselves). And transferring from people to animals may not

work, because the epitopes that antibodies bind and T cells react to

are frequently different in animals than they are in humans, so the

transfer won't work.

So, we are sort of stuck. It's easy to find and measure

autoreactivities of both B and T cells. It's hard to prove that those

autoreactive T or B cells actually do anything. And we do know that

autoreactivity increases during chronic infections, during cancer,

after injuries, etc, and it is also present in some healthy normals.

Therefore, the question of whether the autoreactivities are pathogenic

is an open one. One might go further in this direction by asking, do

the immune diseases have autoreactivity that's way stronger than the

autoreactivity caused by, say, an injury such as a burn. This is

something I'm still working on. For instance, there is reactivity

against myelin basic protein in MS, higher than is found in healthy

normals. But there is also reactivity against that same protein that

happens after a stroke. I haven't gotten the papers yet to see if the

reactivities are comparable quantitatively.

While you can't transfer into a human, you can transfer into an

explant and look for pathogenic effects. The agonist anti-TSHr

antibodies of Graves' disease will cause thyroid cells to go gonzo in

vitro. This can be shown with about 90% of patient sera. So I think

Graves' is a real autoimmune disease. The thyroid in Graves' is not

really inflamed, according to what I read. There's just this antibody

which binds and activates the TSH receptor.

Similarly, in myasthenia gravis, in about 90% of patients you can

demonstrate an anti-acetylcholine-receptor antibody which is an

antagonist.

So I think those are really autoimmune diseases. But what causes the

autoimmunity? I'm not sure. There's at least a bit of precedent for

that idea. Persistent infection is one possibility. Paroxysmal cold

hemoglobinuria is an autoimmune hemolysis that is pretty common in

syphilis. There are also some reactions I haven't read about yet,

found in TB, such as Takeyasu's [sp?] arteritis, which may be of an

autoimmune nature since no TB bacilli can be found at the site.

Another probable autoimmune disease is pemphigus vulgaris. In this one

I think antibody transfer to mice has been effective in reproducing

the disease lesions. And I think some of the anti-RBC and anti-platlet

autoimmunities are pretty well documented. Prior to the demonstration

of the latter blood autoreactivities, most authorities held that

autoimmunity was impossible.

In SLE, conservative minds say that for the most part, the

pathogenicity of particular Abs is not demonstrated. However, I think

that most people accept that the pathology of lupus is caused by

immune complex deposition in the microvasculature, and we can all see

that SLE patients have these ungodly titers of autoAb in their blood.

So I think people consider it all but shown that SOME of these Ab are

causing the disease.

But, again, why? Persistant infection? No infection? A hit-and-run

infection which has been cleared, but damaged the immune system while

it was present? Unfortunately, it doesn't look like people have found

out very much about whether a autoreactivities ought to be reversible

or not. The classic experimental AI diseases -- such as Experimental

Autoimmune Encaphalitis and Collagen-induced Arthritis -- resolve,

suggesting that autoreactivity can be beaten back down. I know there

are also relapsing versions of EAE, but I haven't found out yet

whether any of them are in wild-type animals. I think all the

relapsing versions of experimental autoimmune diseases MAY(?) take

place in inbred mice, which, as I wrote about yesterday, have been

bred to their siblings for at least 20 generations. These guys may

have serious genetic problems that aren't indicative of what goes on

in wild mammals like you and me.

Then you have the issues of AIDS and immunoablation. AIDS causes

remission in a lot of the immune diseases. In some of them, reliable

studies have been done to prove that; in others it's just a bunch of

anecdotes. Obviously, TB doesn't remit when you get AIDS, so what's

going on? Why do those diseases remit? Somewhat similarly, a lot of

the immune diseases can be near-cured in about 50% of people by

massive toxic treatments that kill white cells (particularly

lymphocytes). In many cases the treatment is so severe that you need

an autologous stem cell transplant afterward, or else your immune

system would never regenerate and you'd die. Yet in the other half of

patients who get this procedure, not a lot happens. What does that

mean? Unfortunately, there are no reports of CFS patients getting

AIDS. I do have anecdotes from CFS patients who had a major response

to leucocyte-toxic drugs used in both immunoablation and in cancer

treatment.

So basically I'm undecided about MS, RA, SLE, and pretty much all the

rest. Really, the whole " MS is autoimmune " thing is just a fig leaf.

None of the really serious MS etiologists consider MS to be " proven "

to be autoimmune. They consider that to be " most likely true, " at best.

Did you have high levels of the SLE autoantibodies, consistently? If

so, it would be interesting to see if they are consistently absent

now, after your antimicrobial treatment. I know a lab where you might

be able to get them checked (you'd have to pay for it though).

>

> I for one am interested in what you think.

>

> SInce in my own experience (life-time really) I have grappled with

> the auto autoimmunity throries (as linked to suseptibility by tissue

> type- or genetics- flaws or otherwise) versus chronic problems

> becuase of shronic pathogen load - I have come to think that latter

> is the cause of ALOT of diagnosed autoimmune disease becuase of the

> resultant HYPERSENSITIVITY of the immune system being constantly

> stimulated.

>

> Personally- after being around animals my entire life- I don't think

> thrie immune sytems are any different than humans- it's just most

> bugs are SPECIES specific - and beleive me - ther are alot of animals

> that don't feel well- we just don't norice- or don't care.

>

> In my own case (remember - spenic function is in question with me)

> there is no doubt my 'autoimmune dx's' were because of pathogen

> burden the immune system couldn't handle.

>

> But host and pathogens DO evolve together - where it's a single life-

> time or many... and really- looking at history- the hosts don't

> really have the upper hand- and never have..

>

> I think it's just more complicated than Docs want it to be- OH-

> you're tissue type Blah Blah - so you're going to get Blah Blah - and

> we can't cure it but we have some drugs for you to take the rest of

> your life that MAY make you feel even worse (but you'll be ALIVE -

> abiet not kicking)...

>

> I RATHER see Western Docs/researchers devise tests to look at the

> specific anomolies in individuals (or groups) immune systems as the

> catalyst to devise INDIVIDUAL plans of therapy to improve quality of

> life- ID the pathogens and them target them in an intelligent way..

> But alas- I think mainstream medicine just isn't geared that way.

>

> Chinese medicine- or the ancient ways are more geared to balance-

> strong immunity - less stress, etc. they're just not into the drug

> scene the way Western Medicine is.

>

> Well I'm blathering...

>

> I'm interested to hear your thoughts now - now that you

> understand the immune system better than you did 2 years ago.

>

> Barb

[Guest guest]

Thanks for you're detailed response. You're thinking is pretty

much along the same lines as mine... But I think true idiopathic

autoimmune disease is a rare bird in and of itself - and that the

autoimmunity we see in humans (and now animals) is a secondary

symptom of a hyper Immune system that can't erradicate something

it's after. We know the immune stsme will keep trying (i.e.h.pylori)

even if it damages the body.

I've pulled out acouple of your paragraphs:

ERIC WROET IN PART:

One might go further in this direction by asking, do

the immune diseases have autoreactivity that's way stronger than the

autoreactivity caused by, say, an injury such as a burn. This is

something I'm still working on. For instance, there is reactivity

against myelin basic protein in MS, higher than is found in healthy

normals. But there is also reactivity against that same protein that

happens after a stroke. I haven't gotten the papers yet to see if the

reactivities are comparable quantitatively.

************ Barb reply: Yes I think the autoreactivity is higher

and a potential exists if a condition persists in a person. And

autoreactivity probably isn't the only secondary symptom.

ERIC WROTE:

Unfortunately, it doesn't look like people have found

> out very much about whether a autoreactivities ought to be

reversible.

*****************Barb reply: In my case it was reversible - even

after 30 years. That's the part I find amazing. Although I should

add that I took mopre antioxidants than god - so even though damage

was being done- I may have been keeping somewaht even with the board

in the area of repair- although we know I full of scar tissue

everywhere- but still kicking!

ERIC WROTE:

> Did you have high levels of the SLE autoantibodies, consistently?

If

> so, it would be interesting to see if they are consistently absent

> now, after your antimicrobial treatment. I know a lab where you

might

> be able to get them checked (you'd have to pay for it though).

********************* Yes I had very high ANA counts more than once-

But it wan't CONSISTANTLY elevated. And I had some auto antibodies

against smooth muscle/heart etc.. but I never tested positive on the

double stranded DNA test - so SLE was dx'd but there was always a

big question mark about it.. plus that dx was 1978 - and I didn't

get it treated - and I didn't die (like they said I would) - so they

were wrong.

Personally- I just keep coming back to autoimmunity being a seconday

sypton to an increaded pathogen load a host can't handle- and what

people can handle and what they can't is individual. But I don't

think autoimmune syndromes are diseases - caused by a FLAWED immune

system. Of course alot of the medical profession doesn't agree with

me.

I'm getting my chance with a Derma-pathoolgist next month. I've

attached a picture of my circular sunken lesion in the photo's

section. They worry me- there's a hole beneath the skin on some of

these. If this guy can't think of something new- I've decided to

turn to straight Chinese medicine and give it a go.

Barb

>

> Well,

[Guest guest]

Well, Barb, I agree with you 100% on the "autoimmunity" cop out, which is what I think it is. It's one of the most ludicrous theories I've heard, that the body for no reason other than it "gets confused" decides to attack itself. As for the medical profession, most of them have done nothing significant for me other than mess me up :-) , so I'm going to stick with something more reasonable...that the body is fighting a pathogen which the docs are too dense or lazy to identify. And that the immune response can do a lot of residual damage as it tries to fight off these invaders (think ulcers, cancers, arthritis, and so on). It's possible that once the IS gets activated it's hard to slow itself down (think the inflammatory loop), but you and Tony are evidence to the contrary. You got the upper hand on your pathogens and your bodies started functioning normally. penny Barb Peck <egroups1bp@...> wrote: Thanks for you're detailed response. You're thinking is pretty much along the same lines as mine... But I think true idiopathic autoimmune disease is a rare bird in and of itself - and that the autoimmunity we see in humans (and now animals) is a secondary symptom of a hyper Immune system that can't erradicate something it's after. We know the immune stsme will keep trying (i.e.h.pylori)even if it damages the body.I've

pulled out acouple of your paragraphs:ERIC WROET IN PART:One might go further in this direction by asking, dothe immune diseases have autoreactivity that's way stronger than theautoreactivity caused by, say, an injury such as a burn. This issomething I'm still working on. For instance, there is reactivityagainst myelin basic protein in MS, higher than is found in healthynormals. But there is also reactivity against that same protein thathappens after a stroke. I haven't gotten the papers yet to see if thereactivities are comparable quantitatively.************ Barb reply: Yes I think the autoreactivity is higher and a potential exists if a condition persists in a person. And autoreactivity probably isn't the only secondary symptom.ERIC WROTE:Unfortunately, it doesn't look like people have found> out very much about whether a autoreactivities ought to be reversible.*****************Barb

reply: In my case it was reversible - even after 30 years. That's the part I find amazing. Although I should add that I took mopre antioxidants than god - so even though damage was being done- I may have been keeping somewaht even with the board in the area of repair- although we know I full of scar tissue everywhere- but still kicking!ERIC WROTE:> Did you have high levels of the SLE autoantibodies, consistently? If> so, it would be interesting to see if they are consistently absent> now, after your antimicrobial treatment. I know a lab where you might> be able to get them checked (you'd have to pay for it though).********************* Yes I had very high ANA counts more than once- But it wan't CONSISTANTLY elevated. And I had some auto antibodies against smooth muscle/heart etc.. but I never tested positive on the double stranded DNA test - so SLE was dx'd but there was always a

big question mark about it.. plus that dx was 1978 - and I didn't get it treated - and I didn't die (like they said I would) - so they were wrong.Personally- I just keep coming back to autoimmunity being a seconday sypton to an increaded pathogen load a host can't handle- and what people can handle and what they can't is individual. But I don't think autoimmune syndromes are diseases - caused by a FLAWED immune system. Of course alot of the medical profession doesn't agree with me.I'm getting my chance with a Derma-pathoolgist next month. I've attached a picture of my circular sunken lesion in the photo's section. They worry me- there's a hole beneath the skin on some of these. If this guy can't think of something new- I've decided to turn to straight Chinese medicine and give it a go.Barb>> Well,

[Guest guest]

> Personally- I just keep coming back to autoimmunity being a seconday

> sypton to an increaded pathogen load a host can't handle- and what

> people can handle and what they can't is individual.

The key question is, are the autoreactivities found in non-AI diseases

like tuberculosis, *quantitatively* comparable to the autoreactivities

found in the mystery immune diseases. I haven't answered this yet for

myself. I want to get into the lit on that very thoroughly.

> But I don't

> think autoimmune syndromes are diseases - caused by a FLAWED immune

> system. Of course alot of the medical profession doesn't agree with

> me.

In some cases I think they are very impressed by how they can transfer

the immune diseases in spontaneous mouse models (inbred mice that get

immune disease, without being auto-antigen vaccinated like

experimental autoimmune encephalitis mice are to model MS). I haven't

read the details, but I think you can take a lupus mouse and a

diabetes mouse, switch their immune systems via lymphoablative bone

marrow transplant, and viola, the lupus mouse will have diabetes and

the diabetes mouse will have lupus.

The question is who these spontaneous immune disease mice are, and

what if anything do they have anything to do with. They are inbred

(sibling-bred) and homozygous. That's not as unnatural as it sounds, I

mean it's not going to mess things up biologically that much per se as

far as I know... inbreeding will cause expression of various monogenic

genetic diseases - that's why it's not allowed! - but offspring with

those diseases will be selected out of the line once and for all. And

completed inbred lines are almost clones of each other, which is nice.

The question is, just how many odd (odd but wild-type) alleles were

bred into them in the first place, when they were created? No one

seems to ever go into that. I don't understand why not. And the big

question is, is there any chance any of the alleles are mutant

(non-wild-type) ones? That's where you really risk creating something

that's irrelevant to natural disease (assuming mutant alleles are not

involved in human immune disease).

There's good reason to worry about this. There are a ZILLION genes you

can damage in a mouse - single genes - that will cause it to get an

autoimmune-looking disease (which almost certainly is an autoimmune

disease). Since most new mutations are loss-of-function mutations,

they are usually comparable to a gene knockout. Accordingly,

_Fundemental Immunol_ Ed 5 contains the following:

" The growing number of mouse strains whose autoimmunity

occurs following deletion of immune system genes has

at once generated many important basic insights yet at

the same time raised questions about whether lesions

in the targeted pathways are responsible for [model?

human? both?] spontaneous autoimmune diseases. "

The wording is a little vague, so I can't be exactly certain they are

thinking the same thing I am describing above.

> I'm getting my chance with a Derma-pathoolgist next month. I've

> attached a picture of my circular sunken lesion in the photo's

> section.

I can't find your file.

> They worry me- there's a hole beneath the skin on some of

> these. If this guy can't think of something new- I've decided to

> turn to straight Chinese medicine and give it a go.

Far out... I hope something works.

[Guest guest]

> Well, Barb, I agree with you 100% on the " autoimmunity " cop out,

which is what I think it is. It's one of the most ludicrous theories

I've heard, that the body for no reason other than it " gets confused "

decides to attack itself.

I haven't actually read the papers, but I think disease-causing

autoimmunity is pretty much proven to occur in myasthenia gravis,

Grave's, pemphigus, some hemolyses, some platlet-depletions,

pernicious anemia, and maybe more. But we don't know what causes those

autoreactivities. Persistent infection is certainly one possibility.

With the other diseases, it's more up in the air. But those guys have

a million little alignments in their theoretics just like we have in

ours about microbes. In short the whole business is impossibly

byzantine and contingent, but I think it's pretty far from total BS.

[Guest guest]

There may be a few cases where it's possible that the body does go haywire, but to dump so many diseases into the "autoimmunity" realm is TOTAL BS and I'll stand by that 'til I die. I'm confident that it will eventually come out as one of the truly stupid medical assumptions. One of your examples is Graves, which is related to a thyroid hormonal imbalance. I know a lot of people who have Graves and there is definitely a link between the Graves and various chronic infections they have. There are studies to support it too, but no one pays any attention. Also, the L.A. times just a few weeks ago came out saying that there is now evidence that Diabetes is not just exacerbated by, but caused by dental infections. It's already been proven that heart disease and mouth cancer can be caused by dental infections. If your

mouth can cause diabetes, or cancer, or hormonal imbalances, how many other kinds of illnesses are being caused by pathogens that aren't being identified? The so-called "autoimmune" diseases seem like the no brainer place to start. penny <usenethod@...> wrote: > Well, Barb, I agree with you 100% on the "autoimmunity" cop out,which is what I think it is. It's one of the most ludicrous theoriesI've heard, that the body for

no reason other than it "gets confused"decides to attack itself. I haven't actually read the papers, but I think disease-causingautoimmunity is pretty much proven to occur in myasthenia gravis,Grave's, pemphigus, some hemolyses, some platlet-depletions,pernicious anemia, and maybe more. But we don't know what causes thoseautoreactivities. Persistent infection is certainly one possibility. With the other diseases, it's more up in the air. But those guys havea million little alignments in their theoretics just like we have inours about microbes. In short the whole business is impossiblybyzantine and contingent, but I think it's pretty far from total BS.

[Guest guest]

> There may be a few cases where it's possible that the body does go

haywire, but to dump so many diseases into the " autoimmunity " realm is

TOTAL BS and I'll stand by that 'til I die.

Well, I think myasthenia is rare, but Graves' comprises no few cases:

" Prevalence:. Graves' disease has been estimated to occur in 0.4% of

the population of the United States with a lifetime risk of 1%. ...

www.med.harvard.edu/JPNM/TF94_95/Sept13/WriteUpSept13.html - 15k -

Cached - Similar pages "

> I'm confident that it will eventually come out as one of the truly

stupid medical assumptions.

Yes, it may be very overblown and there are some really smart people

who agree, like Plotz who has a lab at NIH.

> One of your examples is Graves, which is related to a thyroid

hormonal imbalance.

Yes... it causes the imbalance.

> I know a lot of people who have Graves and there is definitely a

link between the Graves and various chronic infections they have.

There are studies to support it too, but no one pays any attention.

Well, there's the association with yersinia seropositivity, which I

think you told me about. It's discussed in wikipedia. Still, most

Graves' patients aren't seropositive for yersinia.

Anyway, supposedly, if you take the sera from Graves', you can use

that to activate thyroid cells in vitro to overproduce T3 and T4. This

is universally accepted, though I haven't read the papers myeslf (to

make sure the sera was used at physiological concentration, etc). So,

that makes it an autoimmune disease in my book, because autoimmunity

is upstream of the disease process. As I said, there may be something

upstream of the autoimmunity, including perhaps persistent infection,

in some or all cases. But nothing like that has been proved, that I

know of.

Obviously there has to be SOMETHING upstream of the autoimmunity.

These days it is extremely common for scientists to say something

like, " without doubt, the causes of Permanent Everything Syndrome are

very complex, reflecting a mix of blah blah sorts of factors. " This

kind of statement is either trivial or unjustified, depending on how

you interpret it, but in any case not a good statement to make IMO,

since what we see so far in the mystery diseases are windows and

associations, not long skeins of solid fact. Ewald goes apeshit

about this in " Plague Time. " Bearing in mind the caveat that 19th

century medicine was probably not as disciplined as today's, Ewald

trots out some now-silly-looking lists of accepted contributers to

tuberculosis circa 1870. Some of them, like alcoholism and

inheritance, probably really are significant contributors, but some

aren't. What's really silly is that those old authors presented their

lists as incomplete, but solid and foundational insight about the

cause of TB, but it wasn't. In fact their insights were totally

peripheral.

However, Ewald almost seems to suggest that it's unlikely or

impossible that " what's upstream " could be stochastic. Ie, just a

bunch of random crap (with zillions of variables) that turns out to

decide whether or not you get a disease. He seems to think that if

only 40% of identical twins of Crohn's patients also have Crohn's,

then there must very probably be " something to discover " that makes

the difference of why some people don't get it even though they are

genetically identical to someone who did. I think Ewald's rhetoric

went a little far, though. Who knows, maybe there is a benign

mycobacterium in the gut, and there are 68 other benign mycobacteria

in the environment, and if you get exposed to them in a certain

special order it makes your immune system overreact to the first one,

and you get Crohn's, even though your brother didn't. In that case,

there'd be nothing to discover, because it'd be so complex that it

couldn't be discovered. Who knows whether such a thing is unlikely or

pretty likely?

But I think we would both agree with the thrust of Ewald's diatribe,

which is that a whole bunch of spending - more - should go toward new

ideas looking for " the discovery/ies " in case they are there.

Basically, being sick I share some of your resentment, since

autoimmunity studies take up vast amounts of funding and the certainty

of the concepts is widely overrepresented, IMO.

You might like this guy, who is pretty conservative on the proof of

autoimmune disease. His short introductory paper to this book can be

read for free if you register for Amazon:

http://www.amazon.com/Decade-Autoimmunity-Y-Shoenfeld/dp/0444828249/ref=sr_1_1/1\

03-9583037-8175001?ie=UTF8 & s=books & qid=1179767631 & sr=8-1

> Also, the L.A. times just a few weeks ago came out saying that there

is now evidence that Diabetes is not just exacerbated by, but caused

by dental infections.

I'd be interested to read it if you have the URL.

[Guest guest]

For some reason my computer burped as I hit send to post the

pictures. I'll do it again later.

I don't think any resercher cares to do a quantitative analysis

comparing the autoreactivities in no AI disease to AI disease.

The closest they come is TH1 vs TH2 and even they know they DON'T

know jact about these pathways- more and more is discovered every

year. They could be wrong about alot of things they think is

correct now _ historically this is VERY true- one minute somethings

safe, the next it isn't - of whoops maybe it is.. it's not called

an exact science for nothin'

Barb

>

>

> > Personally- I just keep coming back to autoimmunity being a

seconday

> > sypton to an increaded pathogen load a host can't handle- and

what

> > people can handle and what they can't is individual.

>

> The key question is, are the autoreactivities found in non-AI

diseases

> like tuberculosis, *quantitatively* comparable to the

autoreactivities

> found in the mystery immune diseases. I haven't answered this yet

for

> myself. I want to get into the lit on that very thoroughly.

>

>

> > But I don't

> > think autoimmune syndromes are diseases - caused by a FLAWED

immune

> > system. Of course alot of the medical profession doesn't agree

with

> > me.

>

> In some cases I think they are very impressed by how they can

transfer

> the immune diseases in spontaneous mouse models (inbred mice that

get

> immune disease, without being auto-antigen vaccinated like

> experimental autoimmune encephalitis mice are to model MS). I

haven't

> read the details, but I think you can take a lupus mouse and a

> diabetes mouse, switch their immune systems via lymphoablative bone

> marrow transplant, and viola, the lupus mouse will have diabetes

and

> the diabetes mouse will have lupus.

>

> The question is who these spontaneous immune disease mice are, and

> what if anything do they have anything to do with. They are inbred

> (sibling-bred) and homozygous. That's not as unnatural as it

sounds, I

> mean it's not going to mess things up biologically that much per

se as

> far as I know... inbreeding will cause expression of various

monogenic

> genetic diseases - that's why it's not allowed! - but offspring

with

> those diseases will be selected out of the line once and for all.

And

> completed inbred lines are almost clones of each other, which is

nice.

> The question is, just how many odd (odd but wild-type) alleles were

> bred into them in the first place, when they were created? No one

> seems to ever go into that. I don't understand why not. And the big

> question is, is there any chance any of the alleles are mutant

> (non-wild-type) ones? That's where you really risk creating

something

> that's irrelevant to natural disease (assuming mutant alleles are

not

> involved in human immune disease).

>

> There's good reason to worry about this. There are a ZILLION genes

you

> can damage in a mouse - single genes - that will cause it to get an

> autoimmune-looking disease (which almost certainly is an autoimmune

> disease). Since most new mutations are loss-of-function mutations,

> they are usually comparable to a gene knockout. Accordingly,

> _Fundemental Immunol_ Ed 5 contains the following:

>

> " The growing number of mouse strains whose autoimmunity

> occurs following deletion of immune system genes has

> at once generated many important basic insights yet at

> the same time raised questions about whether lesions

> in the targeted pathways are responsible for [model?

> human? both?] spontaneous autoimmune diseases. "

>

> The wording is a little vague, so I can't be exactly certain they

are

> thinking the same thing I am describing above.

>

>

>

> > I'm getting my chance with a Derma-pathoolgist next month. I've

> > attached a picture of my circular sunken lesion in the photo's

> > section.

>

> I can't find your file.

>

>

> > They worry me- there's a hole beneath the skin on some of

> > these. If this guy can't think of something new- I've decided

to

> > turn to straight Chinese medicine and give it a go.

>

> Far out... I hope something works.

>

[Guest guest]

A derma pathologist? That's interesting. & Good for you for sticking with it to find someone who sounds like he might actually have a clue. :-) penny Barb Peck <egroups1bp@...> wrote: For some reason my computer burped as I hit send to post the pictures. I'll do it again later.I don't think any resercher cares to do a quantitative analysis comparing the autoreactivities in no AI disease to AI disease.The closest they come is TH1 vs TH2 and

even they know they DON'T know jact about these pathways- more and more is discovered every year. They could be wrong about alot of things they think is correct now _ historically this is VERY true- one minute somethings safe, the next it isn't - of whoops maybe it is.. it's not called an exact science for nothin'Barb>> > > Personally- I just keep coming back to autoimmunity being a seconday > > sypton to an increaded pathogen load a host can't handle- and what > > people can handle and what they can't is individual. > > The key question is, are the autoreactivities found in non-AI diseases> like tuberculosis, *quantitatively* comparable to the autoreactivities> found in the

mystery immune diseases. I haven't answered this yet for> myself. I want to get into the lit on that very thoroughly.> > > > But I don't > > think autoimmune syndromes are diseases - caused by a FLAWED immune > > system. Of course alot of the medical profession doesn't agree with > > me.> > In some cases I think they are very impressed by how they can transfer> the immune diseases in spontaneous mouse models (inbred mice that get> immune disease, without being auto-antigen vaccinated like> experimental autoimmune encephalitis mice are to model MS). I haven't> read the details, but I think you can take a lupus mouse and a> diabetes mouse, switch their immune systems via lymphoablative bone> marrow transplant, and viola, the lupus mouse will have diabetes and> the diabetes mouse will have lupus. > > The question

is who these spontaneous immune disease mice are, and> what if anything do they have anything to do with. They are inbred> (sibling-bred) and homozygous. That's not as unnatural as it sounds, I> mean it's not going to mess things up biologically that much per se as> far as I know... inbreeding will cause expression of various monogenic> genetic diseases - that's why it's not allowed! - but offspring with> those diseases will be selected out of the line once and for all. And> completed inbred lines are almost clones of each other, which is nice.> The question is, just how many odd (odd but wild-type) alleles were> bred into them in the first place, when they were created? No one> seems to ever go into that. I don't understand why not. And the big> question is, is there any chance any of the alleles are mutant> (non-wild-type) ones? That's where you really risk

creating something> that's irrelevant to natural disease (assuming mutant alleles are not> involved in human immune disease). > > There's good reason to worry about this. There are a ZILLION genes you> can damage in a mouse - single genes - that will cause it to get an> autoimmune-looking disease (which almost certainly is an autoimmune> disease). Since most new mutations are loss-of-function mutations,> they are usually comparable to a gene knockout. Accordingly,> _Fundemental Immunol_ Ed 5 contains the following:> > "The growing number of mouse strains whose autoimmunity> occurs following deletion of immune system genes has> at once generated many important basic insights yet at> the same time raised questions about whether lesions> in the targeted pathways are responsible for [model?> human? both?] spontaneous autoimmune diseases."> >

The wording is a little vague, so I can't be exactly certain they are> thinking the same thing I am describing above.> > > > > I'm getting my chance with a Derma-pathoolgist next month. I've > > attached a picture of my circular sunken lesion in the photo's > > section. > > I can't find your file.> > > > They worry me- there's a hole beneath the skin on some of > > these. If this guy can't think of something new- I've decided to > > turn to straight Chinese medicine and give it a go.> > Far out... I hope something works.>

[Guest guest]

On Wed, May 23, 2007 at 02:23:05PM -0000, Barb Peck wrote:

>I don't think any resercher cares to do a quantitative analysis

>comparing the autoreactivities in no AI disease to AI disease.

>The closest they come is TH1 vs TH2 and even they know they DON'T

>know jact about these pathways- more and more is discovered every

>year. They could be wrong about alot of things they think is

>correct now _ historically this is VERY true- one minute somethings

>safe, the next it isn't - of whoops maybe it is.. it's not called

>an exact science for nothin'

Here's a quote from the book pointed to (on Amazon; it's from the

first chapter, which is free):

Everyone is autoimmunopotent. This means that everyone has not

only autoreactive B cells waiting for help of proper T cells, but

is in fact producing many anti-self antibodies. A glance at a

Western blot, showing your own serum full of distinct antibodies

reacting with your own cytoplasmic and nuclear antigens, is

revealing. Serologists working in routine laboratories were

already aware of this phenomenon for a long time. They decided

not to report the presence of autoantibodies, such as rheumatoid

factors, to clinicians, unless the titre is above the level which

is present in 95% of the population. Thus, the presence of

autoantibodies is a completely normal phenomenon, unless the

titres are so high that they sre only found in 5% of the local

population. The adjective " local " is of utmost importance. In

" underdeveloped " areas of the world, for instance, the immune

system is far more active. This results in far higher levels of

autoantibodies in the normal local population.

That's from " The Mystery of Autoimmune Diseases " , by T. E. W. Feltkamp,

in _The Decade of Autoimmunity_, by Y. Shoenfeld (editor):

http://www.amazon.com/Decade-Autoimmunity-Y-Shoenfeld/dp/0444828249

[Guest guest]

Shoenfeld's book seems better and better. I've read it all now,

almost, and am re-reading some.

The Chaim Putterman & Yaakov Naparstek chapter on lupus seems really

great. I notice Naparstek has written in the past with P Plotz, who is

a profound skeptic and one of my favorite few immunologists.

Anyway, they claim that what I learned in undergrad, about SLE being

the classic disease of immune complex deposition, was discredited

during the 90s. They take the standpoint, common now I think, that

anti-dsDNA antibodies are most likely to be pathogenic in SLE, being

much more sensitive and specific to SLE than are any other antibodies.

They go on to review several papers about anti-dsDNA antibodies

*penetrating cells,* and even nuclei, to cause pathology. This is

something I heard of once, but didn't think anyone had confirmed it.

The papers they cite appear to be by multiple groups. A couple other

possible pathogenic mechanisms are discussed. This chapter is one of

the most fascinating things I've read. I plan to look up everything

these guys have written since.

Jean-Francois Bach's chapter on diabetes is also great, very nuts and

bolts, and very probing and exact. There are many other interesting

chapters, including an exploration of whether the ANCA antibodies of

Wegener's (etc) are pathogenic or not.

[Guest guest]

Go back almost 20 years.

Lupus was named in 1967 - so when I got the dx of SLE (lupus) in

1978 - the Docs were giddy they had a case of something 'rare'.

Even then you had to test positive on an anit-DNS test to be TRUE SLE

(and I was negative on it) but was positive on all the 'other'

criteria.

So that idea isn't new. My Doc's said I 'mostlikely' had SLE- and

wanted to draw blood every 3 months form then on forever- (I

basically just said no).

Barb

>

> Shoenfeld's book seems better and better. I've read it all now,

> almost, and am re-reading some.

>

> The Chaim Putterman & Yaakov Naparstek chapter on lupus seems really

> great. I notice Naparstek has written in the past with P Plotz, who

is

> a profound skeptic and one of my favorite few immunologists.

>

> Anyway, they claim that what I learned in undergrad, about SLE being

> the classic disease of immune complex deposition, was discredited

> during the 90s. They take the standpoint, common now I think, that

> anti-dsDNA antibodies are most likely to be pathogenic in SLE, being

> much more sensitive and specific to SLE than are any other

antibodies.

> They go on to review several papers about anti-dsDNA antibodies

> *penetrating cells,* and even nuclei, to cause pathology. This is

> something I heard of once, but didn't think anyone had confirmed it.

> The papers they cite appear to be by multiple groups. A couple other

> possible pathogenic mechanisms are discussed. This chapter is one of

> the most fascinating things I've read. I plan to look up everything

> these guys have written since.

>

> Jean-Francois Bach's chapter on diabetes is also great, very nuts

and

> bolts, and very probing and exact. There are many other interesting

> chapters, including an exploration of whether the ANCA antibodies of

> Wegener's (etc) are pathogenic or not.

>