Stool antibodies presumably originate as secretory antibodies in the small intestines. The only place to my knowledge where these can be obtained is from Dr Ken Fine's lab in Dallas. His website is www.enterolab.com and his prices are reasonable. You may have trouble getting your insurance company to pay for these and you may have trouble getting your doctor(s) to give these tests credence. I was initially a skeptic too but I am now sold on the idea of secretory antibody in the GI tract or stool. I have never met Dr Fine (I shall some day) but I have spoken with him & emailed him on several occasions and he has always been helpful albeit a bit evangelical about his topic.
Several recent articles articles have moved me in that direction but the most persuasive was an article out of a Berlin shop by a group led by Dr Ulrich Wanschaffe, Celiac Disease-like Abnormalities in a Subgroup of Patients with Irritable Bowel Syndrome (GASTROENTEROLOGY 2001;121:1329–1338). I consider this to be a landmark study for several reasons. They studied a group of about 100 clinically diagnosed Irritable Bowel Disease (IBD) patients who tested negative using the usual blood screening tests for celiac disease. 30 % of these patients had "celiac antibodies" in fluid aspirated on endoscopy. Most of these patients also had the "celiac genes" and also had slightly increased lymphocytes in their duodenal biopsy. Furthermore, their symptoms improved on a gluten-free diet!! If this study pans out and is generalizable then we have a whole new group of "silent celiacs" who are seronegative (blood tests are negative) but intestinal (secretory) antibody positive. This type of test might also be more sensitive than a biopsy.
Even though this study was based on "secretory" antibodies in the duodenal aspirate fluid, it makes sense to me that those antibodies will ultimately show up in the stool. This next little bit of research is all that is needed to connect the dots.
Not an evangelist myself, I still predict that we'll have FDA-approved test for celiac antibodies in the stool within a few years.
By the way, a Cuban group recently reported a "one-step" test for blood antibodies that should be a commercially viable product.
This is a messy
area. AGA-G (IgG against gliadin)
is the least SPECIFIC test against CD meaning it can be positive in persons who
DON’T have CD. It is probably the
most SENSITIVE test however, meaning if you have very mild case of it it’s the
most likely test to be positive of them all.
What causes false
positive AGA-G?? Crohn’s disease
(very unlikely without diarrhea), Wheat protein allergy—different antibody
from CD but people get diarrhea, hives, allergic symptoms after ingesting wheat.
Chronic diarrhea or post-infectious diarrhea states also reported to give
false positives.
Your pediatrician
should get a total IgA level as well, IgA
deficiency if fairly common in CD and if you’re IgA deficient you can’t make
the IgA antibodies that are more diagnostic for CD.
He should also probably find a lab that can do (IgA) anti-tissue transglutaminase test. There's a new generation test for anti-tTG that uses human protein. It's significantly more accurate than "last year's" test that used guinea pig protein.
In this setting
with a family history your children MAY have “pre-celiac” disease.
Dr Maki, a noted European CD researcher has proposed this condition.
No one really knows what to do with it yet.
Positive antibody, negative biopsy
If by positive
antibodies you mean either IgA endomysial (EMA), IgA gliadin or IgA tissue
transglutaminase, then I’d agree, you probably have CD.
If it’s an IgG gliadin or any reticulin antibody then it is less
certain since other conditions will give these reactions.
Biopsy should be
interpreted by someone familiar with pathologic findings for CD.
Earliest change is just increase in lymphocytes (immune cells) in the
tissue all the way up to full-blown villous flattening.
Many centers use the “Marsh index” to “score” the pathology
findings in presumptive cases of CD.
Ask your GI to get
a second opinion on your slides from someone who does GI path.
Strict GF diet
should result in decreases in antibody titers over time.
EMA (tTG) will go down first, usually negative by 4-6 months.
IgA gliadin next then IgG gliadin which may persist for a year.
Another study has shown that patients (who were ultimately diagnosed with CD) with equivocal biopsies when given large "doses" of gluten containing protein over 2 month period will develop the typical changes of villous flattening. This is also known as a "Gluten Challenge".
If presumptive CD then be sure to get the rest of the workup for iron/vitamin deficiency, osteoporosis, etc. Low bone density, e.g., would corroborate the positive antibodies.
It is well
documented that autoimmune thyroiditis “travels” with CD just like type 1
diabetes and a bunch of other “autoimmune” conditions.
CD Overview, silent CD, iceberg
Celiac disease in
children has two general types of presentation.
The “classical” presentation of celiac would be an infant who
presents with chronic diarrhea, malnutrition, weight loss, and “failure to
thrive”. This presentation has been shown to be decreasing in some
European studies. This decrease may
be due to the increase in breast-feeding and delay in exposure of the very
sensitive infant gut to the “toxic protein”, gliadin, in grain products.
The more mature gut of children and adults is more resistant to the
penetration of large molecules. Thus,
celiac disease in older children and adults usually presents much more slowly.
It is fairly common that several years pass between onset of clinical
manifestations and diagnosis.
There has been a
lot of interest in the celiac literature recently in so-called “silent celiac
disease” or “pre-celiac disease”. The
damage to the gut caused by gluten exposure occurs sporadically and irregularly
in the early stages of the disease. Malabsorption
of vitamins and minerals probably occurs first.
Iron and calcium malabsorption are most common.
These produce iron deficiency anemia and osteoporosis, or thinning of the
bones. As the celiac disease
continues to progress multiple vitamin and mineral deficiencies occur.
Patients also begin to experience malabsorption of protein, carbohydrate,
and fat. Carbohydrate malabsorption causes patients did complain of a
lot of gas, particularly flatus (“pooting”).
Fat malabsorption causes loose stools and diarrhea.
Patients who are on a lower fat intake may also experience constipation.
Protein malabsorption can cause muscle wasting.
Many patients
complain of fatigue, weakness, depression, vague gastrointestinal complaints,
arthritis and joint complaints, skin rashes, and just generally not feeling
well.
Children with the
more silent form may also manifest poor tooth formation and poor gain in height.
The symptoms are
sufficiently vague that some patients will attribute them to stress, poor sleep,
or other things. The medical “differential
diagnosis” includes such things as fibromyalgia, chronic fatigue syndrome,
thyroid gland disorders, irritable bowel syndrome, gastroesophageal reflux, and
so on. There are other problems
that are commonly manifest in patients with celiac disease including recurrent
mouth ulcers, rashes, particularly atopic dermatitis, infertility in women and
impotence in man, hypoglycemia, and alopecia areata (a patchy form of hair
loss).
It is clear that
there is an “iceberg” effect that is generally worse in North America than
in the European countries. Studies
have been done looking at positive blood tests in Europe and America and appears
that about 1:150 Caucasians in Europe and America are affected.
Approximately 1:250 African-Americans appear to be affected as well.
Celiac disease has been documented in most races, however, it seems that
the genes that predetermine celiac disease probably originated in Europe.
General guidelines
are under development to help physicians determine who they should “screen”
for celiac disease. There are
simple and relatively inexpensive blood tests available that will detect celiac
disease in most patients who have symptoms and in many patients who don’t even
have symptoms. The screening
guidelines includes such things as patients who have relatives with celiac
disease or patients with type 1 so-called juvenile onset diabetes.
It has recently been shown that about 7 % of juvenile diabetics also have
celiac disease. Even those who do
not test positive are still at risk for it in the future. Also screening criteria include such things as iron
deficiency, osteoporosis, tooth enamel defects in children, and other clinical
situations. There is a rash called
dermatitis herpetiformis which is, practically speaking, never seen in children
that occurs in up to the third of adult celiac patients.
The large majority
of patients who go on a “gluten-free diet” will experience complete
resolution of their symptoms. As
far as we know now, the diet must be maintained for life.
Patients with celiac disease who do not adhere to the diet have a greatly
increased risk of developing lymphoma (a form of cancer) in the small
intestines. Patients who stay on
the gluten-free diet lessen this risk.
Earliest finding is
intraepithelial lymphocytosis, then crypt hyperplasia, then villous flattening.
A healed gut can take a while to respond—most studies show that the
villi structures are normal at 6 months but it may take up to 2 years for the
increased intraepithelial lymphocytosis to resolve.
A few other things
can cause the findings you describe but you have a 10-15% lifetime risk (perhaps
more) to get CD.
Dr Maki’s
neoepitope theory isn’t completely accepted but It makes a lot of sense to me.
It’s clear that
tTG enzyme is very heavily expressed in dying (apoptotic) cells and IMHO is
responsible for the upward spiral, dramatic, sort of crescendo that is often
seen (my case, e.g.) where symptoms & findings increase dramatically over a
brief time after a long period of pre-symptomatic disease.
The anti-tTG that
is produced then binds locally and remotely (skin, nerves, e.g.).
As in any antibody-antigen reaction, the two titrate (bind up, tie up)
one another. As long as there’s
more antibody than antigen, you can measure it in the blood.
Once apoptosis
ceases, and this happens rather quickly after the toxic protein is eliminated,
then there are no more tTG=gliadin epitopes and the immune reaction cools off.
The anti-tTG level then deteriorates based on its native half-life, about
6 months for IgA I think, plus, it binds to any available epitope so it falls a
little faster than if it had nothing to bind to.
Most of the
serologic recovery studies have been done with (anti) EMA & AGA.
The anti-tTG kits
have been standardized against EMA & biopsy for the most part.
I haven’t seen anything (although I’m sure someone’s working on it)
that documents the anti-tTG short term behavior—most have assumed that it
correlates with EMA since these tests appear to me measuring the same antibody.
Anti-tTG is also
thought to be less specific than EMA. This
means this: if your EMA is positive, you have 100% chance of having CD
(100% specific). Recent studies of
anti-tTG have shown it to only be 90-95% specific, in other words, it does have
a few false positives associated with it. (test
is positive but villi normal on biopsy).
Muscles prefer to
burn glutamine and the gut uses glutamine almost exclusively for its internal
nutrition. Interestingly, gliadin
is about 40% glutamine.
There’s a theory
called the glutamine hypothesis that heavy exercise, extreme stress,
malnutrition, etc cause immune suppression because of relative glutamine
deficit; I have also speculated as have others that glutamine relative
deficiency is very common in active celiac and this has actually been shown by a
couple of researchers. This could also cause slow gut recovery.
Other tests to consider if not CD
Consider Giardia.
It is much more common than most people think & you don’t have to
drink well water. It is epidemic in
nursing homes, day care centers, and in gay men.
There’s a stool test called Giardia specific antigen that will pick up
85-90% with one sample. If you’ve traveled or live in the deep south roundworms
also but your blood count would have shown eosinophils so worms unlikely.
If you have HIV
risk factors you should be tested for that.
Gas & bloating
are really very characteristic for Giardia but fits other malabsorption patterns
as well. “pre-celiac” unlikely
to give this much in way of symptoms with non-specific biopsy findings.
Also endocrine
stuff—hyperthyroidism causes diarrhea, also a weird syndrome called carcinoid.
The labs would be (everything I can think of now):
Stool for white cells,
pH, reducing subs, Giardia antigen, isospora, cryptosporidium, C difficile
Blood for TSH &
direct T4 (thyroid), 5-HIAA (carcinoid), Zinc level, carotene level
D-xylose test helps
determines if pancreatic insufficiency vs. bowel
Breath labeled CO2 test
for carbohydrate malabsorption
Allergy workup for
wheat, casein, soy, etc protein allergy
Irritable Bowel
Syndrome—very common
Empiric treatment with
Flagyl
Endocrine workup for
other neuroendocrine causes—VIP, etc
Repeat EGD &
biopsies
Blood
work - they should test for what??
1--IgA tissue
(anti-) transglutaminase OR IgA (anti-) endomysial.
These antibodies measure the same thing (damage to endomysium in the GI
mucosa) and both disappear in 4-6 months after going GF.
If either of these is positive, you probably have CD.
The anti-endomysial is said to be 100% specific—if it’s positive, you
have it.
2--IgA and IgG
anti-gliadin are more indirect and last longer in the blood.
If IgA is positive you probably have it.
If only IgG is positive, the workup gets a little messy.
Other things can make this antibody go up. Your doctor should know.
3--There is a new test for IgG tissue (anti-) transglutaminase. This will be available soon and will add sensitivity to the panel.
4--total IgA. Around 5% of celiac patients are IgA deficient so they don't make the antibodies that are used for the diagnosis. If total IgA is low then there's a very strong possibility of celiac disease.
what are the
normal levels??
Biopsy-
of what, how, looking for what??
Doctor will give an
intravenous sedative, put a scope in to your stomach, then your duodenum as far
as he/she can go then take from 6-12 tiny pieces of the lining of your small
intestines through the scope. Pieces
are very small, 2-3 mm in size.
30 grams of gluten per day for 2 months will induce the expected changes on biopsy and may also cause the blood antibodies to become positive or increase. 30 grams is a lot; 1 piece of bread contains about 4 grams of total protein and only about half of this is gluten. I cases where diagnosis is difficult (eg, antibody tests are non-diagnostic) I tell patients to eat bread or pasta with every meal for 6-8 weeks before biopsy.
Diagnostic tests after diagnosis made
CBC—recheck on
your anemia & iron replacement.
Chemistry panel—esp
liver functions (reported abnormal in some CDs) albumin/total protein (general
nutritional state), Ca/PO4 (parathyroid metabolism), BUN/creatinine (kidney fxn—esp
with your diabetes).
Anti-endomysial IgA
antibody—this most closely correlates with GI damage.
It takes 4-8 months to return to normal.
Tissue transglutaminase test-same indicator as endomysial but cheaper, this is the test to follow in long run.
IgA & IgG
(anti) Gliadin are other CD markers. Takes
even longer to go down.
Iron & iron
binding if it wasn’t done earlier, otherwise wait until CBC is OK.
Ferritin unreliable with inflammation.
DEXA scan of femur
& spine. If > 2.5 standard deviations down, then
you have osteoporosis. Good news—most CD osteoporosis corrects
with Ca & vit D replacement.
Also consider B12
& folate levels—these are usually OK in CD—most anemia is Fe.
Vitamin, Mineral supplementation
Iron only if needed according to lab testing. If newly diagnosed and iron deficient consider postponing iron supplementation for first 2-3 weeks so early gut recovery can occur. Iron can then be better absorbed & will cause less constipation.
"High Potency" multivitamin (eg, GNC Mega-man, Wild Oats multi)
additional supplements to a total of:
Calcium, 1500-2000 mg per day.
Magnesium, 1000 mg per day
Zinc, 50 mg per day
Selenium 100-200 mcg per day
Vitamin D3 (cholecalciferol) 600-800 IU per day (Many vits only have D2, ergocalciferol, which requires sunlight exposure to the skin to convert to D3).
Other trace minerals present in multivitamin cap: manganese, chromium, copper.
ALSO consider:
Glutamine--probably helpful during early healing phase. Less helpful later on
"enzyme" supplement-some studies suggest helpful during early recovery.
Vitamin E total 400 IU natural or 800 IU synthetic
Omega 3 fatty acid supplement-2 gram of Fish oil or 1/2-1 Tbsp Flax seed oil daily.
Ginkgo Biloba
Aspirin (mini-dose) please discuss with your doctor
Fiber supplement, dietary--prunes also GF psyllium, Crushed Flax seeds (lots of GF supplements at local health food store)