article gluten sensitivity (celiac and non-celiac)

[harma]

Found a Dutch Celiac board, maybe published here before, it's about Celiac and non celiac gluten sensitivity. I don't know why, but personally I find it very difficult to understand why they can be sure that Celiac and the non-celiac gluten reaction are two totally different things (that what I make of this article). But maybe gluten are that bad for us, that the immune system has not only one system but several systems to react on it. Or should it still be the fear that celiac is something like the real gluten reaction and the non-celiac sensitivity, wel something like IBS. They (have to) admit that some people, without any medical explanation do much better on a gluten free diet. But there is no explanation for it and well probably "between their ears". But what about than Dr fine's stool test???

Well positive part is, at least there is more and more attention for gluten sensitivity.
Sapone et al. BMC Medicine 2011, 9:23
Published: 9 March 2011

Divergence of gut permeability and mucosal immune gene expression in two glutenassociated conditions:
celiac disease and gluten sensitivity

Abstract
Background:
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten.
Glutensensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue
transglutaminase autoantibodies or autoimmune comorbidities.

By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS,
we sought to better understand the similarities and differences between these two gluten-associated disorders.

Methods:
CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.

Results:
Unlike CD, GS is not associated with increased intestinal permeability.
In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286).
Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295).
Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293).

Conclusions:
This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.

Table 1
Clinical and laboratory characteristics of the study subjects

Figure 1
Reduced intestinal permeability in gluten-sensitive (GS) patients

Figure 2
The relative expression of tight junction (TJ)-related genes in the mucosa of gluten-sensitive patients (GS) versus celiac disease patients (CD

Figure 3
Reduced numbers of intraepithelial lymphocytes (IELs) in gluten-sensitive patients (GS) versus celiac disease patients (CD).

Figure 4
Increased levels of transcripts for effector cytokines in the mucosa from celiac disease patients (CD) but not gluten-sensitive patients (GS).

Figure 5
Increased levels of transcripts for pattern recognition receptors in the mucosa from gluten-sensitive patients (GS) but not celiac disease patients (CD).

Figure 6
Reduced levels of transcripts of immune regulatory genes in the mucosa from gluten-sensitive patients (GS), but not celiac disease patients (CD).


Conclusions
The results of this study suggest that CD and GS are distinct clinical entities caused by different intestinal mucosal responses to gluten.
CD results from a complex, and as yet undetermined, interplay of increased intestinal permeability, mucosal damage, environmental factors in addition to gluten, and genetic predisposition, which involves both MHC and non-MHC genes.
The typical intestinal lesions in CD are thought to be mediated by both innate and adaptive immune effector pathways.
Our findings suggest that, in a different way, GS is associated with prevalent activation of an innate immune response.
Although the mechanisms responsible for the loss of intestinal barrier function in CD have been delineated in part, the factors responsible for the loss of gluten tolerance
and the development of autoimmunity in this condition are still incompletely understood.

We believe that this study could contribute to the clinical characterization of GS as a condition associated with prevalent gluten-induced activation of innate immunity in the absence of detectable changes in mucosal barrier function, and that it provides additional clues to the definition of the complex gluten-induced changes in TJ regulation and immune processes underlying CD pathogenesis.

Doubleblind, placebo-controlled studies are necessary to further solidify the definition of GS patients and to search for specific biomarkers for a proper diagnosis.


Author details
1Department of Internal and Experimental Medicine Magrassi-Lanzara,
Seconda Università degli Studi di Napoli, Naples, Italy. 2Mucosal Biology
Research Center, University of Maryland School of Medicine, Baltimore, MD,
USA. 3Johns Hopkins Asthma and Allergy Center, Johns Hopkins University
School of Medicine, Baltimore, MD, USA. 4Department of Experimental
Medicine, Seconda Università di Napoli, Naples, Italy. 5Institute of Food,
Consiglio Nazionale delle Ricerche (CNR), Avellino, Italy. 6Department of
Pediatrics, Seconda Università degli Studi di Napoli, Naples, Italy. 7Servizio di
Endoscopia Digestiva, Seconda Università degli Studi di Napoli, Naples, Italy.
8Morfopatologia, Seconda Università degli Studi di Napoli, Naples, Italy.
Volledig artikel:
http://www.biomedcentral.com/content/pd ... 5-9-23.pdf

[tex]

Hi Harma,

I believe that's the same research report that we discussed back in March. My opinion hasn't changed - I think that Dr. Fasano is just trying to find a way to cover his butt, and avoid eating a lot of crow, some day, as he slowly does a complete 180 degree reversal of his originally-incorrect claims about gluten sensitivity, as related to celiac disease, and so-called non-celic gluten-sensitivity. Like most GI docs, he can't bring himself to admit that he was wrong, so he has become an expert at "beating around the bush", in order to cover up what he should actually be saying. The link below, contains most of my thoughts about the article, and some insight by Rosie, who originally brought the article to my attention.

http://www.perskyfarms.com/phpBB2/viewtopic.php?t=13469

Tex

[sarkin]

Well, at least they're admitting that non-celiac gluten sensitivity exists. If they were actually any good at diagnosing celiac disease, this would make more sense (and - I wonder how many of the non-celiac patients in this study were simply undiagnosed... in which case they are looking at the difference between celiacs with more and less damage, not celiacs and nonceliac GS people at all, at least in some cases).

I can't help noticing who this helps: "Doubleblind, placebo-controlled studies are necessary to further solidify the definition of GS patients and to search for specific biomarkers for a proper diagnosis." Aside from the fact that Dr. Fine has no trouble whatsoever finding antibodies, which you think would be a useful marker, GS patients can help themselves, for free, by eliminating gluten. The patients don't need a proper diagnosis - eating something and feeling horrible, discontinuing it and feeling better is something a house pet can do (even my dog, bless him). Wild animals do it all the time.

They'll probably come up with a new kind of special, horrible intestinal damage that's required to be diagnosed GS, and then fail to diagnose that for 10-13 years on average, just as they now do with celiac disease. And they will call that progress ;)

Thanks for sharing this, Harma - I have seen this before, I believe (I remember the date, because it was right around the time I found this forum).

Hope you're feeling good,

Sara

[tex]

If they were actually any good at diagnosing celiac disease, this would make more sense (and - I wonder how many of the non-celiac patients in this study were simply undiagnosed... in which case they are looking at the difference between celiacs with more and less damage, not celiacs and nonceliac GS people at all, at least in some cases).

Exactly. Dr. Fasano is so "eat up" with professional snobbery, that he refuses to recognize the validity of Enterolab's stool tests, and as a result of that, he continues to rely on the extremely poor and unreliable sensitivity of the blood tests, when attempting to diagnose the disease. Because of that poor choice of diagnostic tests, he misses the diagnosis of far more celiacs than he actually successfully diagnoses.

Tex

[harma]

Even I did have their doubt about the test of Dr Fine, this research towards non-diagnosed celiac gluten intolerance would be a golden chance to include this test. See if it makes sense, this stool test, people's symptoms, their recovery after a gluten free diet and again testing again.

But if celiac gluten minded scientists are twisting and turning, that means something is moving. I think that is a positive sign, not there yet but on the way

[sarkin]

You're right, Harma. I think Tex is also right - meaning that Dr. Fasano is so busy trying not to look wrong, he just can't get it right. But someone else with brains could take a look and get a clue, and beat Dr. F. at what he thinks is his very own private game.

These SOBs who want to 'own' the celiac patient community really have another think coming ;) I suspect I may well be a celiac patient myself, but it doesn't even matter if "they" ever diagnose me. So - la di da!

As many of you must know, here's the derivation of patient:


Origin:
1275–1325; Middle English pacient (adj. and noun) < Middle French < Latin patient- (stem of patiēns ), present participle of patī to undergo, suffer, bear; see -ent

No thanks! (An older meaning is, explicitly, sufferer/victim.)

The derivation of doctor has to do with teaching - well, unless they'd like to learn a little something... No thanks to that as well!

If Dr. F. doesn't eat gluten-free pasta, then he's really more interested in not being wrong than in getting things right, IMHO. If he thinks his future zonulin-deactivator potion will be a consequence-free win, he's not read very much sci-fi (or has an otherwise sadly limited imagination). It's my opinion that turning off the effects of zonulin will not 'fix' what he thinks it will, any more than lowering cholesterol has 'fixed' heart disease. Oops, I'm switching rants midstream now...

I'm obviously speculating wildly about his motives and plans. But I can do that from the sidelines - I'm thrilled not to be doing it as a 'patient' of his or of anyone else's who can't eat a little GF crow from time to time. (I'm looking at you, former doctor of Arlene.)

--Sara

[tex]

Harma,

You're right - Dr. Fasano could very easily prove, once and for all, that Dr. Fine's tests used at Enterolab are valid, and they would be very, very beneficial for using in his work in diagnosing celiac disease, but obviously, he doesn't want to do that, because of his resentment, (jealousy?), toward Dr. Fine. Dr. Fasano's attitude in this situation would seem to be more attune to the personality of what I refer to as an academic prima donna, rather than a scientist.

Tex