Fw: [fibroml] Studying the Autoimmune Disease Puzzle

[Guest guest]

This is long, but very interesting!!

W

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>

> June 19, 2001

>

> Studying the Autoimmune Disease Puzzle

>

> By NATALIE ANGIER

>

> Whether it's through drinking too hard or driving too fast, or picking

> fights with fists or pistols, men as a rule are said to engage in more

> self-destructive behaviors than women.

>

> But why should women bother, when their bodies so often do the

> self-destructing for them?

>

> For reasons that researchers are just beginning to understand, women are

> at a much greater risk than men of falling prey to an autoimmune

> disease, in which the body's immune system turns paranoid and begins to

> attack one or more of the body's organs.

>

> The list of autoimmune diseases is long and varied, composed of more

> than 80 disorders afflicting virtually every sector of mortal flesh and

> function: the liver, the kidneys, the adrenal glands, the ovaries, the

> pancreas, the skin, the joints, the muscles, the myelin sheaths that

> buffer the nerves, the salivary ducts that spit, the tear ducts that

> weep.

>

> Some of the conditions are cosmetically annoying but otherwise harmless,

> like vitiligo, in which patches of skin lose pigmentation. Others are

> debilitating yet manageable, while still others can be severe,

> progressive and even fatal. Systemic scleroderma, for example, a disease

> of the connective tissue that results in hyperproduction of collagen,

> can sometimes wreak unstoppable havoc on the body's organs, hardening

> them into woodlike uselessness.

>

> And in all but a few autoimmune disorders, the sex ratio is wildly

> skewed toward women. In Hashimoto's disease, for example, in which the

> immune system assaults the thyroid gland, the proportion of female to

> male victims is 50 to 1. For systemic lupus erythematosus, an

> inflammation of connective tissue, the ratio is 9 to 1; for Graves'

> hyperthyroidism, 7 to 1. Even the less frankly " feminine " immune

> diseases like multiple sclerosis and Type 1, or juvenile, diabetes

> strike twice as many women as men.

>

> " The numbers are pretty staggering, " said Dr. Caroline C. Whitacre, a

> professor of molecular virology, immunology and medical genetics at Ohio

> State. " Of the eight and a half million people with autoimmune diseases

> in this country, 6.7 million, or nearly 80 percent, are women. "

>

> Now, propelled by an invigorated women's health movement and a

> heightened ability to explore the molecular mechanisms of the autoimmune

> response, researchers at last are making headway in understanding how

> and why the body sometimes wages war on itself. They are learning why

> women are particularly susceptible to aberrations of the immune system,

> and they are devising novel approaches to blocking the misguided attacks

> and allowing the scapegoated organs to heal.

>

> One of the most intriguing new findings arises from the discovery that,

> during pregnancy, a mother and fetus exchange body cells that can

> persist in one or the other's circulation for years or even decades

> after birth. Now it seems that this lovely long- term bond can on rare

> occasions have dire consequences, producing an autoimmune reaction in

> either the bearer or the born.

>

> In another study that will appear next month in The Journal of Clinical

> Investigation, L. Faustman of the immunobiology laboratory of

> Harvard Medical School and her colleagues at Massachusetts General

> Hospital report that they effectively cured laboratory mice of Type 1

> diabetes through a relatively short and simple therapy. The treatment, a

> 40-day course of injections with a drug called CFA, induces the body to

> produce so-called tumor necrosis factor alpha, a signaling molecule of

> the immune system. This necrosis factor in turn prompts the aberrant

> autoimmune cells to commit suicide through a carefully orchestrated

> program called apoptosis.

>

> As Dr. Faustman describes, the mice that have been purged of autoimmune

> cells quickly regrow their islet cells, allowing the pancreas to reclaim

> its rightful role as insulin sweatshop. Three-quarters of the time, the

> mice remain free of diabetes for the rest of their lives, making this

> perhaps the first genuine cure for the harrowing disorder in a

> laboratory animal.

>

> The treatment is a long way from proving its mettle in human patients,

> but Dr. Faustman suggests that it eventually may prove effective against

> a wide array of autoimmune conditions in addition to juvenile diabetes.

>

> Indeed, many immunologists argue that the autoimmune diseases, which

> have been regarded as distinct conditions, each deserving of their own

> subspecialty and advocacy group, are better viewed as variations on a

> single grim theme.

>

> " Only recently have we begun thinking of autoimmune diseases as a

> consortium, a related group of conditions that have many features in

> common, " said Noel R. Rose, a professor at s Hopkins and head of the

> American Autoimmune Disease Association. " By focusing on these common

> elements, we've advanced our understanding. "

>

> For one thing, Dr. Rose pointed out, doctors have become aware that

> those who suffer from one autoimmune disease are at increased risk of

> contracting another. Moreover, researchers have seen that a generalized

> predisposition toward autoimmunity may run in families, with one person

> suffering from, say, lupus, another from rheumatoid arthritis, a third

> from Graves' disease. Knowing this kinship pattern, Dr. Rose said, may

> help a doctor more quickly diagnose an autoimmune condition.

>

> Genetic predispostion, though, is only a part of the story of

> autoimmunity. A number of researchers are seeking to understand the link

> between immune disorders and sex hormones. Women's comparatively high

> levels of the so-called female hormone, estrogen, and low levels of the

> male-affiliated androgens are thought to explain some of the sex

> discrepancies in autoimmune disease, which is why many women first

> suffer the symptoms of an autoimmune syndrome in their 20's, when

> average monthly estrogen levels are at their peak.

>

> In addition, the hormones of pregnancy clearly influence a number of

> autoimmune diseases, in some cases ameliorating the condition, in other

> instances possibly making it worse. Dr. Whitacre points out that women

> with rheumatoid arthritis or multiple sclerosis often experience a great

> improvement in their disorder while pregnant, particularly during the

> last trimester, when all the intersecting hormonal systems of pregnancy

> are humming at maximum capacity.

>

> The glorious holiday of health, alas, is short-lived. " At delivery,

> there's dramatic drop-off in both estrogen and progesterone levels, and

> you see an almost immediate return of the disease, " Dr. Whitacre said.

> " In the first three months after delivery, the disease may be much, much

> worse than it was before pregnancy. " Eventually, she added, it reverts

> to its previous, prepregnancy state.

>

> But autoimmunity is more than a simple matter of estrogen dosing. Not

> only have contraceptive pills proved disappointing as a treatment

> against most autoimmune conditions, but for some disorders, the high-E

> months of pregnancy feel less like a Club Med getaway than a foray to

> the Bates Motel. Women with lupus, for example, may find that their

> arthritic pains, mouth and nose sores, malaise, fatigue and butterfly

> facial rashes worsen during gestation, to the point where those who have

> had one child are reluctant to risk childbearing again.

>

> Such observations, together with animal studies, have prompted

> researchers to examine other possible hormonal culprits. At a recent

> meeting in San Francisco of the American Association for the Advancement

> of Science, Dr. Sara of the University of Missouri reported that

> prolactin, a pituitary hormone that soars late in pregnancy to begin

> stimulating milk production, can intensify lupus symptoms, and she

> described the modest but prolonged success of treating lupus with

> bromocriptine, a prolactin suppressant.

>

> Dr. also proposed that women may be at risk for autoimmune

> conditions not because they have too much estrogen, but because they

> have too little testosterone. She presented results in which lupus

> patients were treated over long periods of time with

> dehydroepiandrosterone, or DHEA, an androgen much weaker than

> testosterone and thus less likely to have unpleasant masculinizing side

> effects. Although not cured by any means, the patients on DHEA reported

> feeling more energetic and less symptomatic, and less likely to need an

> immune- suppressant drug, prednisone, than the group taking dummy pills.

>

> Pregnancy may also influence autoimmune risk through entirely

> nonhormonal means. In research so new that scientists still aren't sure

> what to make of it, Dr. J. Lee of the Fred Hutchinson Cancer

> Research Center in Seattle and her colleagues have found that the perils

> of pregnancy may be akin to those of an organ transplant.

>

> As a researcher at a cancer center, Dr. often observed the ugly

> effects of so- called graft-versus-host disease, when patients receive

> an imperfectly matched bone marrow transplant as part of their cancer

> treatment, and the immune cells of the installed marrow begin attacking

> their new home. Dr. noticed that the symptoms of

> graft-versus-host disease looked a lot like scleroderma and other severe

> autoimmune conditions.

>

> When she learned in the mid-1990's of work showing that fetal cells

> persist in very low numbers in a mother's circulation for years, even

> decades, after birth, " a light bulb went off, " Dr. said. Could

> this state of persistent microchimerism - the mixed population of her

> own and fetal cells in a mother's body - explain some cases of

> autoimmune disease?

>

> Recent research suggests that the answer is yes. Measuring the amount of

> fetal cell DNA in the blood of women whose scleroderma first arose after

> they had children, Dr. and her co-workers found that there was,

> on average, 20 times the number of persistent fetal cells in the

> scleroderma patients than in women who had given birth but who did not

> have scleroderma (although that still amounted to a very tiny number of

> fetal cells in any woman, sclerodermic or otherwise).

>

> Moreover, the researchers have found that, as with graft-versus-host

> disease, the greatest risk seems to occur when there is a close but not

> identical match between mother host and fetal " graft. " The key lies in

> the relative compatibility of so-called HLA molecules, which help an

> individual's immune system distinguish between host and guest. When a

> mother's HLA molecule is very different from her baby's, her immune

> system seems able to clean up the fetal cells postpartum, and the

> cellular umbilicus is safely severed. But when the HLA molecules are a

> little too close for comfort, the maternal immune system apparently gets

> confused: which is real, and which the imposter? That bewilderment seems

> to help touch off an inappropriate autoimmune reaction against the

> mother's own molecules.

>

> Lest mothers get smug about the ingratitude of children, Dr. said

> this is not a one-way risk: maternal cells can linger in a fetus's

> bloodstream, too. This cellular mother load, as it were, could explain

> some cases of autoimmune disease in men.

>

> Preliminary evidence even suggests that there is such a thing as

> multigenerational microchimerism, in which a woman with an autoimmune

> disorder can blame both her mother and her children for her misery. In

> these bizarre instances, the woman harbors circulating cells from her

> mother and from her offspring that turn out to be more compatible in

> their HLA palette with each other than either is with the mother in the

> middle.

>

> " If your mother is HLA compatible with your child, it gives you a

> sevenfold or higher risk for scleroderma, " Dr. said. " It's a

> uniquely female risk to have these transgenerational effects, this war

> taking place in the body. "

>

> Dr. acknowledges that microchimerism accounts for only one piece

> of the autoimmune puzzle, but she hopes the new insights may lead to

> treatments that aim at the lingering souvenirs of symbioses past.

>

> If you can't choose your family, you should at least be able to choose

> your family feuds. Copyright 2001 The New York Times Company

>

> ************************************************************

> Chip and Jane Kohler

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[Guest guest]

Dear , my doctors have told me over the years that most of my problems have to do with hormones. I do think the one problem the message board has is that we are not naming the prescritions we're on. I''m on the "normal" hrt but the doctor wanted me to go on Avista, I was concerned because I didn't want periods again. Next time I go I'll ask again. It just may be the same thing. Love, Sue

[Guest guest]

Good question !

I have no idea about my levels of testosterone, but since I am going through the change, my hormone levels were low. Now I'm on HRT, so I'm not sure if that brings them back up to where they were or not. Good question to ask my doctor though.

W

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.. I have no testosterone in my body at all, and my estrogen level will not hold. Does anybody else have hormone problems.? Just curious.

[Guest guest]

In a message dated 6/24/01 3:56:33 PM Pacific Daylight Time, grandm4@...

writes:

<< I do think the one problem the message board has is

that we are not naming the prescritions we're on. I''m on the " normal " hrt

but the doctor wanted me to go on Avista, >>

Sue, After my hysterectomy (they left an ovary, the wrong one) I wasn't

suppose to be on any HRT. Well needless to say I had NO estrogen in my body

(the dr finally believed me after 2 weeks of complaining) so I was put on

Premarin. I was on different doses of that for 7 years. Last year when

hormone levels were run, I had no estrogen and very little others. So a NEW

dr switched me to Estrace. Seemed to be working until recently. Think i

need to up the dose.

Thanks for your input. We do need to list what meds we are on.

hugs

[Guest guest]

Does anybody else have hormone problems.? Just curious.

ME, but you already know that! lol

LU