Gene research

[bromley]

Gene Behind Autoimmune Diseases Identified by Researchers 27 March 2007

A report in the March 22 issue of the New England Journal of Medicine reveals that a pinpointed region of chromosome 17, a gene named NALP1, could be a new target of treatment for autoimmune diseases. This is a particularly exciting discovery because NALP1, a gene known to control part of the immune system that serves to alert the body to viral and bacterial attacks, has not previously been specifically implicated in autoimmune diseases, affirms the American Autoimmune Related Diseases Association (AARDA), a national nonprofit patient advocacy organisation. The discovery was the result of collaboration between St. George University of London, the University of Colorado at Denver and Health Sciences Center (UCDHSC), and the Barbara Davis Center for Childhood Disorders.

Why does the body choose the misdirected path of attacking itself, in an autoimmune process, when it sets out to eliminate invaders, such as bacteria or viruses, thus resulting in autoimmune diseases--for example, lupus, multiple sclerosis, rheumatoid arthritis, vitiligo, thyroiditis (Graves', Hashimoto's), juvenile (type 1) diabetes, or any one of the more than 100 such diseases?

The findings of this latest research study, which followed 656 persons from 114 extended families in the United States and the United Kingdom who had multiple autoimmune diseases, give the researchers a clue as to why the immune system attacks one of the body's own tissues. "If the sensor NALP1 is overreactive, it could trigger a response to the wrong stimulus," said Professor Dorothy Bennett, Professor of Cell Biology at St. George's University of London, investigator for the UK arm of the study. She added, "We hope to study exactly how this works and to learn even more from the other genes that we are working to identify."

Lead investigator Dr. Richard Spritz, director of the Human Medical Genetics Program at UCDHSC, was quoted as saying, "Since NALP1 appears to be part of our body's early-warning system for viral or bacterial attack, this gives us ideas about how to try to discover the environmental triggers of these diseases." Dr. Spritz said, "This finding may also open up new approaches to treatment, possibly for many different autoimmune diseases."

Dr. Peter Gregerson, director of the Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research in Manhasset, NY, calls the study "provocative." He said, "It raises the issue of whether this gene might be involved in more common disorders." He also commented that this research is a good example of "a successful, family-based approach to gene identification and an example of how new genes identified that way can raise new connections among different diseases."

It has been estimated that 50 million Americans are affected by autoimmune diseases which rank among the top ten causes of death in women. Recognition of the family connection, as alluded to by Dr. Gregerson, is important because the ability to develop an autoimmune disease is determined by a dominant genetic trait that is very common (20 percent of the population) and may present in families as different autoimmune diseases within the same family. It is important for families with members who have autoimmune diseases to mention this fact when another member of the family is experiencing medical problems that are difficult to diagnose. "Autoimmune diseases are often difficult to diagnose; however, a family history of autoimmune disease is a major clue" said Virginia Ladd, President of the American Autoimmune Related Diseases Association.

Source: Newswise © 2007 Newswise. All Rights Reserved.

[Toyoterry]

As I've stated before, my family is an example of one of the many with multiple types of autoimmune disease. An aunt with Lupus, a wife with RA, myself and two brothers with MS, a father, myself and a son with psoriasis and my daughter is going to see a specialist next month for suspected Juvenile RA. I'm a firm believer that the answer lies in fixing some defective gene(s) that is responsible for these diseases, whether the trigger is bacterial, viral or environmental.

[Lyon]

There is an alternative way of explaining the variety of autoimmune affecting your family, although admittedly it makes me sound like a whacko.

An increasing number of researchers are convinced that it might involve a situation in which EVERYONE in developed countries experiences a predominant environmental predisposition due to our loss of "evolutionary normal" conditions. Yes, disease activation would require another genetic/environmental predisposition/trigger, but the disease process couldn't start without the predominant event.

It's very important to keep in mind where and when these diseases started arising and it's important to keep in mind that large populations of the world still don't experience them.

Until a little over 100 years ago our populations were as infested with parasites, as the third world populations are now. We didn't experience autoimmune disease then, as they don't experience them now.

We didn't intentionally elminate parasites as much as our changed environment no longer allowed them to complete their life cycle, which obviously was necessary to their continued survival. Clothes washing machines, flush toilets, antibiotics, running water, a cleaner and higher quality food supply, wearing shoes and long clothing and an endless list of things added up to their demise in our population.

Keep an eye on the research regarding these parasites and autoimmune disease and I think you will eventually see that they alter the course of most any "autoimmune" disease which began to rise in incidence as the "developed" countries (which coincidentally happen to be farther from the equator and happens to have an almost exclusively light skinned population) began to experience the "industrial revolution".

Bob

[lyndacarol]

Toyoterry--My bet is there is a "common thread" among all autoimmune diseases ( maybe the same pancreas problem). But specifically with MS in your family, I think it is an "inherited" pancreas. I bet all with MS have faulty pancreatic function; if insulin levels were tested, I think they would all have elevated levels, as I have.

Remember, Lyon, I am that "insulin girl."

[Toyoterry]

Bob,
I think you may be overlooking something when you mention "developed countries". My family is from rural Alabama, which in some people's mind doesn't really qualify for the distinction! Truth is only one member of my parents respective families had a known AI disease. Obviously there could have been many more that I am not aware of but these diseases are all too common in me and my immediate family members who moved to Nebraska (much farther north) Maybe coincidentally, the three of us with MS were the outdoorsman of the family and spent alot of time outdoors both hunting and fishing. I can personally recall having to pull ticks off that were attached after many fishing trips. Infectious cause? Who knows. One could certainly make a case for genetic suseptibility coupled with tick bites I guess. But in all honesty Bob, I would say that our immediate family left an enmviroment where my barefoot hillbilly aunts, uncles and grandparents probably were exposed to more parasites because of their rural environment and general lack of antibiotic use. Again, who knows?
Terry

[CureOrBust]

I bet all with MS have faulty pancreatic function; if insulin levels were tested, I think they would all have elevated levels, as I have.

how much is that bet?

[Rita]

take a look at this article about the relation between type 2 diabetes and hepatitis C virus. I remember to hear about hepatitis and MS relation too.

http://www.lifescan.com/professionals/h ... 12epid006/

[gwa]

The HHV 6A virus is the one some associate with MS.

Several months ago I read an article about diabetes which indicated that the disease was considered a neurological disease after new research led in that direction.

I did not post it because I thought Lynda Carol would post the research.

Maybe there is some tie in with MS, since both diseases may have herpes connections. Someone here probably has a better idea than I do.

gwa

[Lyon]

Hi Terry,

I think you may be overlooking something when you mention "developed countries". My family is from rural Alabama, which in some people's mind doesn't really qualify for the distinction!

That's the truth! My wife's Dad was from Coffee Springs and exactly what you're talking about is why we're thinking of retiring down there. I'm tired of this faced paced world and want to go back to the 1950's! Even though this parasite thing I mentioned is an expansion of the "hygiene hypothesis", probably any reference to "hygiene" is unfortunate because the "hygiene" issue is misleading

But in all honesty Bob, I would say that our immediate family left an environment where my barefoot hillbilly aunts, uncles and grandparents probably were exposed to more parasites because of their rural environment and general lack of antibiotic use. Again, who knows?

That is the key phrase.."who knows?". The truth is that this is a "science" in it's infancy and far less is known than isn't known. On the other hand there is a ton of circumstancial evidence and the whole thing just makes sense.....it almost becomes obvious the more you look into it. That's something that nothing else in the world of MS has ever done. Brainstorming specific situations without knowing the true facts..I know you were partially kidding but I can't say which of your relatives might have been exposed to parasites even though they lived in the rural South. In truth, I've tried to find incidence of specifically the human whipworm in the US and other than isolated pockets in Appalacia which have never seen computers, much less internet, it's absolutely eliminated from the US. My point is that with the situation you find in your family, it might be a subject that you find interesting....if nothing else because the researchers clump the autoimmune diseases into one bucket and that's one of the things I personally have always agreed with.

Bob

[lyndacarol]

Cure--I never learn...I misspoke. I really don't bet. Years ago to teach my son that one can lose in betting, I "bet" him there were no seeds in the "seedless" watermelon I was about to cut open. (By the way, there ARE seeds in a seedless watermelon!)

But, your case notwithstanding, I do still think our problem starts with hyperinsulinemia. I even got a university researcher to admit recently, "I certainly believe insulin (and insulin growth factor) may have a strong influence on brain function (not simply through glucose metabolism) in health and disease."

Not quite the glowing support of hyperinsulinemia yet, but I'm working on him.

And, gwa, you give me too much credit. I'm counting on teamwork here.

[Lyon]

Remember, Lyon, I am that "insulin girl."

Hi Lynda,
Even though I'm among those who dislike the people who feel that dragging someone else down raises their own elevation.......I somehow have gained myself the moniker "parasite boy" which, Lord knows, is not very flattering.

On the other hand, you've gained the moniker "insulin girl" which brings to mind a nice, clear sugary, substance.

Now I wouldn't even raise this issue but I think at this site we pride ourselves in trying to stick as close to accuracy as humanly possible.

My memory is admittedly not the best but I've been paying especially close attention and I'm almost certain that your theory begins with sinus drainage.

Don't you think it would be a little more accurate/fair if your moniker was "snot girl"?

Bob

[lyndacarol]

Oh, Bob....

[Lyon]

Of course I was doing my best to pick on you Lynda but even if insulin were a factor, I don't understand what you think sets it apart as an instigating factor?

I'm off to Florida for a week so everyone here is in for a little vacation!
Bob

[daisy]

Interesting discussion on genetics to parasites

If I understand the Human Genome Project and I freely admit that maybe I don't, but didn't they expect to find somewhere between 100,000 and 150,000 unique genes in the human mankind soup. My understanding is that the project actually found less than 30,000 unique genes in man when mapping was finished. Major disappointment to the pharmaceutical venture capitalists and the industry to which I make my living.

It even seems like the number of genes in a human was plus/minus 1000 to the number of genes in a rodent and only plus/minus a few thousand to a fruit fly. If this is true, then it's unlikely that defective genes are the cause of diseases and that genetics may provide your body with an "autoimmune disease" program stored up in your cells but what turns that program on? Is it ...

Toxins- like heavy metals or pcb's?, genetically modified and engineered food proteins?, leaking guts?, parasites - lack of/wrong species?, viral proteins?, chlamydia, mycoplasma, nanobacteria?, neuropeptides and neurohormones such as insulin and vita D out of whack? Do cell phones and other microwaves vasodilate the BBB and allow large particles into the CNS where they wreak havoc with the epitopes of MOG and MBP? Do "bad fats" scramble up lipid metabolism and create a deficiency of myelin production?

Are autoimmune diseases really just the creation from several or all of these like some "Perfect Storm". Boy I sure would like to know:)

Why do different therapeutic targets and mechanisms of action of therapies benefit some subsets of autoimmune disease patients and not all? Is it the genes of the patients or the underlying enviromental triggers that cause a therapy to benefit one patient but not the next? Why do some with MS seem to do well with CPN antibiotic treatment but only some? Why, when you look at almost all of the drug company clinical trials does the placebo arm usually do pretty well? Can placebo really be a treatment for some? Can we just think/believe ourselves well as the metaphysical folks say and as the placebo response seems to indicate?

Ahhhh... the is it genetics or is it environment debate that runs through all autoimmune disease fields of study.

Based my surely imperfect review of the epidemiologic data on Autoimmune diseases and MS imparticular, I guess I am going to go with my very unscientific intutition and bet my money (if I had any on the environment So many potential causes of autoimmune diseases seem to support a "perfect storm" theory and just seem to make sense a helminth exposed barefoot farm girl from Alabama

Several folks on this website seem to have their own pet theories, CPN, helminths, insulin, Vita D, etc... I think these hypothesis are all correct - at least for some subsets of MS patients.

Which one for which patient? What's the quickest way of trial and error through the causes? What are then the correct therapies to correct each cause?

Someday we will know this... maybe in our life time... just my frustrated ramblings...