Re: NIH Intramural Study

a_weisman_at_yahoo.com
Date: 01/13/05 

Date: 13 Jan 2005 06:07:41 -0800

GregGerber wrote:
> I am saying there is now emerging evidence for sterile autoimmunity
in
> the molecular mimicry sense for a small outlier group of chronic Lyme
> patients. It is probably very rare but may occur, as evidenced in the
> vaccine data.

Well maybe but I sort of doubt it. The failure to find what is causing
the hyperimmunity, doesn't mean there isn't something there. Though I
questioned the indiscriminate use of the phrase "Absence of proof,
isn't proof of absence" the question might fairly be raised here.

I think what led to the theory of molecular mimicry in the first place
was a failure of technology. And what has led to a reconsideration of
it are technological improvements.

Here's what I mean. For a long, long time, scientists and doctors
determined whether there was infection by looking for antibodies to
infection, measuring the humoral aspect of the immune response. Of
course, this is indirect testing in that it looks for the body's
response, rather than the antigen itself but using inferential logic,
it was decided that the presence of antibodies at certain levels meant
the presence of the antigen itself. Antibody responses in the absence
of active infection were thought to be due to "old exposure." This was
"supported" by the fact that in determining "cut offs," which antibody
level was thought due to current vs "old" infection, in cases where
infection was thought to be "old" cultures were unsuccesful and
cultures were used in determining cut offs, along with the presence of
absence of symptoms of "active infection."

So this provided an explanation for ongoing, though low level antibody
responses and a "reliable" way to assess "active" infection too.

"Autoimmunity" was thought to occur when the antigen was "gone" but
antibodies seemed to still be triggering a cellular immune response,
the response where inflamatory chemicals are released and cause
inflamation and even erosion.

The ongoing activity of the cellular immune response was now thought to
be due to the fact that there was enough similarity between antigens
and the body itself. In fact there is a great deal of similarity
between the genetics of all living things; we share much in common with
fruit flies (some of us more than others) and elephants and fish etc.
And antigens have adapted (or we have) as part of evolution, parts of
one anothers genetics; for us as a way to fight and defeat enemies such
as viruss and bacteria; for the viruses and bacteria, adaptive ways to
evade the immune response and survive. Much of this evolution tended to
be adaptive and functional; now viruses could survive without
destroying the host and hosts could survive the assualts of viruses and
other invaders. Evolution tends to be adaptive and functional.

This fact, the inherent functionality of evolution explained by
Darwinian theory "natural selection" is what is troubling about the
theory of molecular mimicry. (Yes I know that in many red states it is
a THEORY only cometing equally with "Intelligent design" as we revisit
the Scopes Monkey trial but assume for the sake of this argument that
Darwin was right or mostly right).

Why is it troubling?

It is troubling because it depends on what is a very dysfunctional view
of our immune systems. Our immune system is generally not all that well
understood but what we do understand is that it is remarkable. And very
adaptive.

So how could the human species have survived if our immune response to
antigens so routinely ends up by attacking us? How is it that evolution
which has allowed both host and invader to mutually coexist so nicely,
has failed to respond to this dysfunction? Are the two mechanisms
actually so mutually exclusive and dysfunctional? Does our body really
attack itself when there is no provocation remaining? Does our immune
system which is so remarkably able to develop UNIQUE responses to each
invader, and even new invaders never before seen, actually fail to
distinguish between me and thee (to borrow a line from Klempner who
borrowed it from others).

But what if it isn't our immune systems that are so dysfunctional, but
rather our paradigm for understanding them?

What if the inferential logic was wrong, at least in part?

What if finding "sterile autoimmunity" is dependent on erroneous
assumptions in a flawed paradigm?

Here's an alternative.

The problem is that we have for years been unable to measure the
presence of SMALL MINUTE amounts of antigen that remain even after what
we have always thought of as "infection" ends? What if the infection
hasn't really ended, but has only moved on to a new stage? Now there is
no more overwhelming infection; antibody levels--the humoral immune
respose--drop and we ASSUME that means the "infection" is gone
entirely. But what if it isn't? The signs and symptoms that we have
associated with "infection" are also gone. We don't have fever or
swollen glands or a cough etc any longer. We can't measure antibodies
any longer or the levels have dropped to the point where we consider
them indicative only of "old" or prior infection. We can no longer
culture the organism from blood.

But there is this nagging ongoing response, maybe it even takes a while
to start to see. It is now "autoimmunity."

But what if it isn't? What if it is a new stage of "infection" and low
levels of the antigen persist. Perhaps they're now in immunologically
privileged locations; and can't be reached by the blood based
response--naturally that humoral antibody response would diminish as it
wasn't doing any good.

But now we have PCR and we can measure the fact that there ARE
persisting antigens long past the time that antibody levels have
dropped to what we thought meant "old" or prior infection; long past
the time when singns and symptoms we have associated with "active"
infection have passed; and long past the time that we can succesfully
culture the organism using traditional culture methods.

But still guess what? We look at joint fluid in arthritic knees and
hips and guess what we see? Bb, staph, strep and other antigens!!! Lo
and behold!

Now are these "active" organisms? I don't think we know that. But as
you and neurolyme have pointed out, the presence of the antigenic
material is causing an immune response; now a cellular level immune
response, one in which cascades of inflamatory chemicals are released
and cause inflamation and even erosion of connective tissue and joints,
even bone itself.

So now we have a theory of persisting inection which triggers an
ongoing immune response, something we've called "hyperimmunity."

This theory not only makes sense, and fits the view of a less
dysfunctional immune system (one more likely to have allowed the
species to survive) but also actually has evidence to support it,
direct evidence.

Whereas molecular mimicy is a theory with no evidence other than
inference based on a series of perhaps dubious assumptions to support
it.

Yet the old theory, the old paradigm persists. As it so often does in
science and medicine, as much of what is "known" is simply "wisdom"
passed down from generation to generation and only occasionally
questioned as to its basic assumptions; revolutionary change in
thinking and basic paradigmatic understanding doesn't come easily or
quickly.

The advances in technology now permit us to find what we couldn't
before, but what was really there anyway. And now we have to dismantle
all the assumptions that were built upon our inability to see things
before, and develop new thinking and ways to understand what we are in
fact able to see now.

Think of it like this. You are born blind. You come to understand the
world using your other senses. You come to have a "picture" of what the
world "looks" like even though you can't see.

Suddenly the blindness is lifted and you can see. But the world is a
strange place, not exactly as you imagined it. Now you have to
recomprehend the world taking into account all the new data provided by
your newly enabled sense of sight.

It takes some time to adjust.

> But there is much better evidence for the larger group for
> hyperinflammation caused by persisting antigen or infection. This is
> the work done by researchers like Phillip and Weis, and it is
probably
> the correct model for most of the chronic patients as the data now
> stands, according to my read of it.

It is probably the correct model for all of what we have previously
thought of as "autoimmunity"

> Why focus on autoimmunity in the mimicry sense? The reason for some
is
> that autoimmunity is their field so they naturally search for
evidence
> for it. This might be the case for Marques.

Yes it is the paradigm by which they came to understand the world.
Either one can adapt to the new data or simply dismiss it. It seems
that the latter may be the response of Marques and Klempner.

> But there is no denying that if anyone were successful not just in
> showing it occurs in Lyme-- which it might well-- but in suggesting
it
> explained all chronic Lyme, it would end the Lyme debate once and for
> all and forever and be the final nail in the coffin, the end. Time
for
> kaddish.

Yit-gadal v'yit-kadash sh'may raba b'alma dee-v'ra che-ru-tay,
ve'yam-lich mal-chutay b'chai-yay-chon uv'yo-may-chon uv-cha-yay d'chol
beit Yisrael, ba-agala u'vitze-man ka-riv, ve'imru amen.
Y'hay sh'may raba me'varach le-alam uleh-almay alma-ya.

Yit-barach v'yish-tabach, v'yit-pa-ar v'yit-romam v'yit-nasay,
v'yit-hadar v'yit-aleh v'yit-halal sh'may d'koo-d'shah, b'rich hoo.
layla (ool-ayla)* meen kol beer-chata v'she-rata, toosh-b'chata
v'nay-ch'mata, da-a meran b'alma, ve'imru amen.

Y'hay sh'lama raba meen sh'maya v'cha-yim aleynu v'al kol Yisrael,
ve'imru amen.

O'seh shalom beem-romav, hoo ya'ah-seh shalom aleynu v'al kol Yisrael,
ve'imru amen.

> It is the impetus on the part of some to suggest this explains the
> entire group that patients must watch out for.

And to extrapolate ALL of their results in a completely overbroad and
unjustifed manner.

But remember, WE signed off on this "chronic Lyme study" and we allowed
this strawman of "chronic lyme" and "long term treatment" to be
erected, with no idea that we might then be forced to tear it down but
be unequipped to do so.

> After all, Klempner and NIH extended the results of their low-dose
> essentially short term treatment study in a skewed atypical patient
set
> to ALL patients and ALL treatment protocols. So why should anything
> else happen with the autoimmune data?

Well objections might be posed by logic and intellectual honesty and
rigorous application of scientific method etc.

Oh, never mind. What was I thinking? Naivetee got the best of me for a
moment there (and the best of Carl and Phyllis for a number of years).

> Hey burn me once and its on you, second time I have to blame myself.
>
> GG

Yes though I think it is fool me once, shame on you, fool me twice,
shame on me.

Although George W Bush reinvented that to be:

"There's an old saying in Tennessee - I know it's in Texas, probably
in Tennessee - that says, fool me once, shame on - shame on you.
Fool me - you can't get fooled again."

Which probably harkens back to his days of drinking and drugging and
listening to the band THE WHO.

(you can watch this brilliant man making the statement at:

http://politicalhumor.about.com/od/bushvideos/v/bushfoolme.htm

and here is a good "bushisms" page:

http://politicalhumor.about.com/od/bushvideos/v/bushfoolme.htm

> a_weisman@yahoo.com wrote:
> > GregGerber wrote:
> > > the autoimmune problem may exist on its own, but in a small
number
> > > only. my $02. pw
> >
> > Yes some may be "autoimmune" in the molecular mimicry "sterile"
sense
> > of autoimmunity that has been typically advanced by the
> > rheumatologists, where your body sees an antigen, say Bb, once, and
> > develops antibodies, rids itself of the Bb but continues to attack
> the
> > body due to the fact that the antigen shares genetic
characteristics
> > with the body, molecular mimicry.
> >
> > However, what is probably a better theory is that low levels of the
> > antigen persist, thus persistent infection, and what is being
> attacked
> > is still the antigen itself, thus the more appropriate term is
> > hyperimmunity rather than autoimmunity.
> >
> > It isn't really a case of the body attacking itself at all (our
> immune
> > systems aren't that dysfunctional or how would we have survived?)
but
> > continuing to attack the antigen, though perhaps the antigen is
> present
> > in smaller quantities than in the initial stages of infection. The
> > ongoing presence of the antigen itself, triggers not just a humoral
> > (blood based) antibody response, but the cellular immune response
> with
> > cytokines, chemokines and other inflamtory chemicals. It is this
> > ongoing aspect of the immune response which triggers the
inflamatory
> > mechanisms which do the greatest amount of damage, cause lesions in
> the
> > brain, produce arthritic symptoms in joints etc. The persistent
> > infection may well be in sites where antibiotics aren't effective
at
> > penetrating, or otherwise immunologically "privileged" sites, where
> > infection is difficult or impossible to eradicate.
> >
> > So perhaps there are those who are truly, classically "autoimmune"
> but
> > I agree with you Greg that most are suffering from a hyperimmunity
> > triggered and fed by ongoing infection. Assuming that is what
you're
> > saying?
> >
> > So the question is, why the focus on this never proven "molecular
> > mimicry" view of autoimmunity, and why a rejection of what appears
to
> > be very good evidence for the other model, where, yes, there is
> > hyperimmunity but also persistent infection? And according to
reports
> > from patients in the studies, the evidence was good that they
> continued
> > to be infected even after having failed treatment before entering
the
> > study, and receiving treatment while in the study?
> >
> > The funny thing is that this old model of autoimmunity was never
> > proven, only theorized and was widely criticized and more and more
of
> > the "modern" thinking is that the persistent infection model for
> which
> > there is some evidence including with Bb, is more accurate and
makes
> > more sense.
> >
> > But Klempner and Marques et al seem fixated on the old model and
seem
> > to go out of their way to ignore any and all evidence to the
contrary
> > particularly evidence of persistent infection.
> >
> > So what gives?

Relevant Pages

  • Re: tulane chronic lyme in rhesus monkeys...results????
    ... histopathology was seen in the tissues, meaning, was there any evidence ... of persistent infection ala what straubinger saw in his dog studies? ... correlate with elimination of the infection, all it means is that the ... IR6 ab response is proof of the elimination of infection? ...
    (sci.med.diseases.lyme)
  • Monkey TLR2s and the Revenge of the "Penis-Ports"
    ... used by glial cells to recognize pathogen-associated molecular ... may help control initial infection. ... Bb antigens, then, may stimulate growth of immature lymphocytic ... purified lipoprotein of M. penetrans LAMPs was able to activate ...
    (sci.med.diseases.lyme)
  • Re: Sally Clark, dead at age 42
    ... He didn't give false evidence. ... serious infection in one of the children immediately prior to death. ... Cot deaths are rare so she must have ... by overwhelming bacterial infection. ...
    (uk.legal)
  • Re: Timescale in which newbies should get control
    ... my BG profile and carb response lately ... sensitivity provided by how my body responds to 1 unit of R insulin. ... response to the infection. ... insulin your blood sugars would d have dropped down swiftly from ...
    (alt.support.diabetes)
  • Re: NIH Intramural Study
    ... > antigen persist, thus persistent infection, and what is being ... > hyperimmunity rather than autoimmunity. ... > in smaller quantities than in the initial stages of infection. ... > be very good evidence for the other model, where, yes, there is ...
    (sci.med.diseases.lyme)