Scientists discover where wheat gluten enters body & how autoimmune dis. develop

[Caryn]

Intestinal Gluten Receptor Is Gateway for Celiac Disease: Finding could offer new treatments for other autoimmune disorders, study says

THURSDAY, July 24 (HealthDay News) -- Researchers believe they have finally answered a basic question about the cause of celiac disease -- where in the body does the wheat protein gluten enter one's system?
A study published in the July issue of Gastroenterology identifies the CXCR3 receptor in the intestine as a gluten gateway. When people with celiac disease eat gluten, the protein triggers their immune system to attack the body, causing a wide range of serious health problems.

"This is a scientific question that had never been answered before," Dr. Alessio Fasano, medical director of the Center for Celiac Research at the University of Maryland School of Medicine, said in an university news release. "It is not only significant in the basic science of autoimmune disorders such as celiac disease, but in therapeutic approaches for the future. This opens a new scientific paradigm for the study of immunity."

The research team found that gliadin, the part of gluten that causes the most trouble for those with celiac disease, binds to the CXCR3 receptor. This results in the release of zonulin, a human protein that lowers the intestinal barrier to make it more permeable. While this effect is temporary in most people, the barrier stays down for long periods of time in people with celiac disease, causing disruption in the body's system.

The finding may help in research on the cause and treatment for other autoimmune diseases, Fasano said. People with type 1 diabetes and multiple sclerosis may experience a similar condition in which offending antigens enter the body through this gateway in the intestines.

"For the first time, we have evidence of how the foreign antigen gains access to the body, causing the autoimmune response," said Fasano, who is also a pediatric gastroenterologist at the University of Maryland Medical Center. "Further study is needed, but this could allow us to intervene before the zonulin is either released or activated, preventing the immune response altogether."

[Lee]

I have a child that has several autoimmune issues, the most serious is a blood clotting autoimmune problem, called Antiphospholipid Antibody Syndrome.  She had IBS at age 9 and a test for Celiac's was high at age 17, just before she suffered a blood clot in her right eye.  She also had Giardia and was asymptomatic until her doctor prescribed Plaquinil to calm down the autoimmune response.  The parasite die off made her sick, she had no symptoms from the parasites.  I am trying to connect the digestive problems she had with her autoimmune issues.  My theory is heal her leaky gut and her autoimmune response will calm down.  Does anyone have any other information or sources, even doctors who are likeminded they can recommend?  This article is very interesting and supports other information I've been able to find.  My hope is a lifestyle change for kids with autoimmune problems will help them to live a long, healthy life! Today she is doing great and is on a Gluten Free diet and taking supplements to heal her gut and stay well!  I was wondering about the ALCAT testing.  Would it be worthwhile to see if she has other food issues, other than Gluten, that might be bothering her digestive tract even though she has no digestive symptoms? 

[Caryn]

Hi Lee,
I really feel for you. You and your daughter have a lot going on right now. Does she have any neurological symptoms? Tingling in the hands and feet?
Does she suffer from frequent headaches?
Many on this board have neuro issues as well and have found help from Defeat Autism Now (DAN) doctors who are trained to recognize imbalances in the body that lead to gut imbalances and neuro/cognitive problems-- even mild cases of ADHD or learning disabilities. They are also generally medical doctors. You could try a naturopath that is familiar with Celiac disease but you may find a naturopath limiting for you when it comes dealing with comorbid autoimmune issues like antiphospholipid Antibody Syndrome.
There is a section on the forum that lists possible DAN doctors but if your daughter doesn't have neuro issues that would not be a good fit for you.
My aunt is dxd with Celiac and finally found a wonderful G.P. that is Celiac herself and knows what lab tests to run and associated autoimmune issues to look out for.
You really need a good doctor that can read between the lines and focus on getting her healthy, someone with nutritional knowledge and an understanding of how Celiac can lead to comorbid conditions. Here's a list of Celiac recommended doctors in the U.S.
Alcat was beneficial for us but is not 100% successful for others. A urine or blood or stool test for microorganisms could get you in the right direction as would a test to measure nutrient absorption. If her gut is really damaged then she needs a low grain low sugar diet until she heals. From personal experience I would suggest no corn, no soy, no milk and no gluten, (of course). I would suggest she omit sugars except stevia or natural organic honey for at least two months, maybe up to 6 depending on how she's doing. She should take supplements based on test results and eat plenty of fruit, vegetables, meats, and dietary fats (but she should avoid peanuts as they are highly fungal and anything with yeast in it.) Has she been tested for Crohns? It could take six months to a year before she will be able to tolerate protein rich foods again. Gut dysbiosis causes lack of absorption, overgrowth of fungi and bad bacteria, and leads to other autoimmune disorders when the krebs cycle is disrupted.
If her teeth are bad (as most Celiac's are) and she has many silver fillings or if she has had known bad reactions to vaccines, especially the flu vaccine, then you may want to test her for metal toxicity. That can disrupt the krebs cycle and cause autoimmune issues too. A small minority of folks have a hard time removing metals from their bodies and store them in their tissues. This is common in Autism Spectrum Disorders but also true in Alzheimer's and Parkinson's patients.
I have a family member dxd with DVT and understand the worries that go along with blood clotting issues. I found a practice that deals with dietary treatments in conjunction with medication while searching for information.
There is a connection between mycoplasma infection and DVT so I think it could be plausible that an infection in the gut could exasperate a clotting disorder. I know that fungal overgrowth can also cause autoimmune issues to worsen.
They say that 80% of our immune system is housed in our gut.
Best of luck in what you decide to do.

[Lee]

Hi Caryn,
     Thanks for all your information and interest in what we've been going through with my daughter.  I really appreciate your input.  I often feel like I'm searching in the dark for answers since our doctors are knowledgeable and compassionate but not able to guide us as to why this happened and how to keep it from happening again.
     Anne Elise did have two different kinds of headaches.  One type lasted off and on for 2 or 3 years ( age 14-16) and we went through neurological testing, a physical, checked her vision and even had TMJ evaluation with the orthodontist and the only thing that was determined was that they were probably hormone related headaches.  She had a second type of headache that occurred when she ate dry food.  The doctors had no answer for that type of headache but with our recent connection to autoimmune problems, we've discovered these headaches were from Sjogren's sydromes, an autoimmune disease that affects the salivary glands among other mucus producing glands.  She has never had problems that were neurological in nature that she resulted in a diagnosis of Autism or ADHD.  She will be a senior next year and has no attention or school related issues.  As far as tingling, she has Reynaud's Syndrome that is related to her circulation.  This was first noticed several years ago but is more noticeable recently and in the winter months.  The tingling is when her hands or feet are cold. 
     Today, Anne Elise is headache free and treating the symptoms of Sjogren's and Reynaud's.  The antiphospholipid Antibody Syndrome (APS) was diagnosed with extensive bloodwork pinpointing the anticardiolipin level being elevated.  Fortunately she regained her eyesight in the eye that had the blood clot. She is on medication to keep her blood thin (baby aspirin and Lovenox injections), and Plaquinil to calm down her immune system.  She is also on numerous supplements to heal her gut and keep her well.  My thinking is how are the recent issues related to her gut since she had IBS at age 9?  I know in MY gut that there is a connection and can't help but think the answer is healing the gut to better control her immune system response.  I asked her pediatrician to check her for Celiacs just before she had the blood clot and the Celiac Panel was elevated.  Unfortunately we were told it was not definitive since she had IBS as a child and it could have affected her Celiac Panel results. Regardless, Anne Elise has followed a gluten free diet at the suggestion of her pediatrician, internist and nutritionist.  She also had giardia that was asymptomatic until she began the Plaquinil.  The giardia was discovered by a "hand cradle assessment" with the help of a naturopath, her medical doctors thought she was having a reaction from the medication or a virus.  Thankfully, after the change in diet, getting rid of the parasites, and her Plaquinil, Anne Elise's anticardiolipin level was normal for the first time since September, this January.  We repeated the bloodwork in April and the anticardiolipin level was elevated.  Unfortunately at the end of February, beginning of March, she caught Mycoplasma.  She recovered quickly.  Caryn, you mentioned mycoplasma and DVT have a connection.  Can you give me more information on this connection or sources I can look at?  Could we have been on the right track by healing her gut and got sidetracked with the mycoplasma?  If I have sources that connect her mycoplasma with DVT, a result of APS, it would explain the April anticardiolipin level being elevated and I would share this with her doctors. 
     I will look at the list of Celiac doctors and see if there are some in our area, south Louisiana.  We had an amazing pediatric gastroenterologist, he believed the key to healing the gut was nutrition first, but he was tragically killed in March in an auto accident.  Today we have my friend, her pediatrician, an internist, nutritionist, naturopath, hemotologist, and rheumotologist, as well as two eye specialists.  We have not had anyone mention Crohn's, but she has not had any intestinal symptoms for over 8 years with the IBS.  You mentioned several tests for microorganisms and nutrient absorption.  Can you give me more information on exactly what type of tests I need to ask for?  I thought the ALCAT test might help to pinpoint food irritants for her digestive system, but have read good and bad reports on the testing.
     One last thing, she has never had problems with her teeth and did not have any adverse reactions to her vaccines.  She did have two of the three Giardia shots over the last couple of years and I have read that shot has triggered autoimmune problems.  Anne Elise's family history predisposed her to Reynaud's and Sjogrens but something triggered them.
     I apologize for this being such a lengthy message but I greatly appreciate any insight you can give me!  It's been a long 9 months of searching for answers.  Thanks a bunch!

[Caryn]

Lee,

Here are a couple of studies on mycoplasma and DVT:

http://www.nmanet.org/images/uploads/Documents/CR956.pdf

"A 13-year-old boy with Mycoplasma pneumoniae pulmonary infection developed deep vein thrombosis and pulmonary embolism. He was found to have protein S deficiency and transient antiphospholipid antibodies. Though uncommon, it is important to consider venous thromboembolic disease in children whose clinical course is atypically severe."

http://www.ncbi.nlm.nih.gov/pubmed/11677283

"A 5 year old boy with serological and clinical evidence of Mycoplasma pneumoniae infection, which was complicated by popliteal artery thrombosis, is described. Intra-arterial urokinase, in conjunction with medical treatment, resulted in clinical recovery and angiographic resolution of the thrombus. The variety of extrapulmonary complications associated with the M pneumoniae infections continues to broaden. Thrombolytic therapies should be considered when similar clinical circumstances arise."

I will post again about possible tests, etc.... when I have a bit more time. These aren't the original study that I found, but the first one, which links the entire paper sounds very similar to your situation.

Here's a link on dietary things to do for clotting problems:
http://www.caringmedical.com/media/article.asp?article_id=445

[Lee]

Hi Caryn,
     I so greatly appreciate your links and will share them with our pediatrician, my good friend.  She and I both felt the progress we were making and the bloodwork was also showing as of January, her anticardiolipin levels were normal, and we believed this was due to improving her leaky gut with a gluten free diet and getting rid of the parasites, and the Plaquinil.  The setback occurred at the end of February with mycoplasma and these articles relate the irregular lupus anticoagulants, anticardiolipin antibodies and low protein S activity. Thank you for helping us make that connection definitively.  I also looked at the diet for blood thinning and she is already following it - lots of vegetables, fresh fruit and lean meats.  We do not do fast food, fried food, margarines or vegetable oils, trans fats, etc.  She is allowed, at the suggestion of her nutritionist, one day off a week and that's been to keep her from giving up altogether.  It's a compromise we agreed upon.  At 17 years old I've learned I have to pick my battles, she understands how important her diet is to heal her leaky gut but she's also been through alot. 
     I looked at the list of doctors for Celiacs and of course there are none in Louisiana.  The nearest would be Houston.  I can have any tests run here if you have suggestions of what might guide us more on her diet.  We are following gluten free because of the elevated Celiac Panel back in the Fall.  Her internist and nutritionist, who are diet and natural health minded, and my friend and her pediatrician, who is learning more about nutrition and healing through Anne Elise, suggested and I also felt the gluten free diet would be a place to start.  The rest of her doctors, other family and friends are not so sure there is a connection.
I don't feel I am proving anything to anyone and need test results to do so.  I do want to be certain we are doing all that we need to do to keep her well.  Our next bloodwork to check her anticardiolipin levels is in July.  I also want to look more at Protein S deficiency and it being a Vitamin K dependent anticoagulant protein...is this hereditary and how it affects her clotting, can anything be addressed with Vitamin K in her diet?
      Again,  thanks so much for your help in helping me put the pieces of this puzzle together!  I sincerely appreciate it!

Lee

[Caryn]

Lee,
I can't answer any specific questions about low protein S activity as I am not familiar with that condition at all.
You may want to check out http://enterolab.com/, specifically the stool testing and possibly the genetic screening for celiac disease. We have used both tests. A stool test is more sensitive than a blood test. But a positive, even a low positive, on a blood test means that the person is sensitive to gluten and should avoid it.
Here is an excerpt from Enterolab:

If my antigliadin antibody levels are only mildly elevated, does that mean I can eat some gluten?
This question is more "wishful thinking" resulting from the mind trying to turn a positive test into what might want to be called "low positive" or even the equivalent of negative. However from our experience, a positive antigliadin antibody of any degree is like a positive pregnancy test. When a pregnancy test is positive, you are not a little pregnant, you are pregnant. The same is true for gluten sensitivity.

Why is my antigliadin antibody elevated if I have been on a gluten-free diet?
There are several reasons why an antigliadin antibody test can be positive despite being on a gluten free diet. The most obvious reason is that there may be hidden gluten in the diet. Gluten is ubiquitous, and if a person does not prepare 100% of their own food, one can not guarantee no gluten intake. Hidden gluten in unsuspected sources or contaminating otherwise gluten-free foods is also possible. But more often, the values are indeed on the lower end of positive, and previous values may have been higher still. So in fact the "elevated value" in fact may represent a marked improvement over previous antibody levels. Sometimes, however, people are so immune suppressed from damage to the intestine and malnutrition that a gluten free diet actually can make the antibody values go up for a time, a reflection of enhanced immune function and response.

What does it mean that my antigliadin antibody level is just below the upper limit of normal?
All clinical laboratory tests must define a normal range that best distinguishes those with disease from those without. Depending on what range is used to define normal will determine how many people with disease will fall into the normal range, and conversely, how many people without disease will fall into the abnormal range. Our determined cut off for normal of 10 Units was derived after years of comparing antibody levels with gene and malabsorptive test results, as well as clinical histories before and after treatment with a gluten free diet. Although our stool test is multitudes more sensitive in picking up gluten sensitivity than blood tests, no single diagnostic test can rule out gluten sensitivity with 100% certainty (we estimate our antibody test misses about 1 in 500, about equal to the frequency of IgA deficiency in the general population). Thus, while it is very unlikely that a person with an antigliadin antibody level in the normal range has active gluten sensitivity, anyone with symptoms of gluten sensitivity and/or having an autoimmune disease, especially if accompanied by an antibody level just below the cut off, or with a gluten sensitive gene and/or intestinal malabsorption, should consider a 6-12 month trial of a gluten free diet, looking for improvement in symptoms, autoimmune disease severity, and/or intestinal malabsorption. It is only in this population that a gluten free diet should be considered a "trial"; all other people must consider gluten-free diet for positive tests definite and permanent therapy.

Is gluten-induced intestinal damage causing malabsorption reversible?
Gluten-induced intestinal damage is fully reversible provided gluten-free dietary treatment is strict and permanent. However, the length of time to full healing and disappearance of malabsorption depends on the severity and disease duration at onset of treatment. Hence, children and those with more mild disease at onset of treatment will resolve malabsorption quicker, usually within 6-12 months. Some adults with severe disease, or those who do not quickly grasp or employ strictness to their gluten-free diet, may have continued nutrient malabsorption for longer periods. If intestinal malabsorption persists beyond 18-24 months, dietary and clinical re-evaluation should be undertaken. Unlike antibody levels, our malabsorption test is a measure of disease severity in the intestine. Values from 300 to 500 malabsorption units represent mild malabsorption; 500-1000 moderate; 1000-1500 severe; and greater than 1500 very severe malabsorption (and possibly indicating a combination of gluten-induced intestinal damage and insufficient pancreatic enzyme secretion).

If you want to run a test for nutrient levels, then I would suggest you look at a Great Plains Laboratories OAT test.

If you want to rule out metal toxicity your doctor can look at tests that you have already done to see if there is a need to be concerned. Dr. Andrew Hall Cutler is a Chemist who wrote a book about Amalgam Illness and in it he lists several lab test results that can possibly point to metal toxicity issues in a patient and warrant further investigation:
Here is a sample of some of the lab results that he mentions point to possible metal toxicity issues--
Elevated 3-methyl histidine in urine
Elevated coproporphyrin in urine
Erythrocytes seen on routine urinalysis at any time during period of illness or one year prior to onset.
IgE > 292 IU
Low total IgG
Low IgG subclass results
Low total T cells
Low CD8 suppressor T cells
Low NK cells
Calculated serum osmolality (the formula is 2XNa + BUN/2.8 + Glucose/18= osmolality) from blood chem panels average >290 under normal conditions of hydration, or patient produces >3 liters of urine in 24 hours, or abnormal relationship between serum osmolality and urine osmolality, or low ADH for given serum osmolality.

These are just a few, but I thought I would give you just a couple to see if there are any commonalities with lab results you already have on hand.

Best of luck in figuring it out.

Caryn

[Caryn]

Lee,
I was doing related research today and found this on a Canadian Lyme Disease website:

"Many Lyme patients were firstly diagnosed with other illnesses such as Juvenile Arthritis, Rheumatoid Arthritis, Reactive Arthritis, Infectious Arthritis, Osteoarthritis, Fibromyalgia, Raynaud's Syndrome, Chronic Fatigue Syndrome, Interstitial Cystis, Gastroesophageal Reflux Disease, Fifth Disease, Multiple Sclerosis, scleroderma, lupus, early ALS, early Alzheimers Disease, crohn's disease, ménières syndrome, reynaud's syndrome, sjogren's syndrome, irritable bowel syndrome, colitis, prostatitis, psychiatric disorders (bipolar, depression, etc.), encephalitis, sleep disorders, thyroid disease and various other illnesses. see Other Diseases and Lyme."

Has your daughter ever been tested for Lyme? Have you any recollection of her getting a bulls eye rash prior to the onset of her many symptoms? It is present in 30% of Lyme cases and could be mistaken for a spider bite or 'ringworm' rash.

[Lee]

Thanks Caryn for forwarding the information on Lyme Disease and the possible connection to various autoimmune diseases.  I do not remember her ever having a spider-like bite or any type of rash that we couldn't identify.  She has seen a dermatologist off and on over the years so I can ask her to look at her records and the timing of the onset of the IBS (age 9).  I did research the mycoplasma and the effect on anticardiolipin levels and antiphospholipid antibody syndrome and there seems to be a link there and the onset of her headaches.  Her pediatrician checked her records and she had mycoplasma 11/06 and was first seen for a severe headache in 6/07 (7 months later).  The first Sjogren's type headache from eating dry food was in 8/07.  I think you were right in suggesting that that mycoplasma might have set the underlying clotting disorder into action, one of the major complaints are headaches.  We are still gluten free and working on healing her gut since the IBS was the first problem 9 years ago and the Celiac Panel was elevated 8/10.  I will think about any possible odd rashes before the IBS though and maybe give her dermatologist a call to check her records. 

Thanks a bunch for all your help!
Lee