CONCLUSIONS: In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.
 
CONCLUSIONS: IgA deficiency occurred in 1:131 patients tested for celiac disease, and celiac disease occurred in 1:6 of those properly evaluated. Inadequate evaluation of IgA deficiency while testing for celiac disease occurred frequently and resulted in the underdiagnosis of both. Changes in testing algorithms and reporting of results were made to improve testing for celiac disease and IgA deficiency.
 
Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2-7 years (median 4.5 years). Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.
IgA endomysium antibodies - an early predictor for celiac disease in children without villous atrophy.
PMID: 18489624  May 2008
 
 
RESULTS: At diagnosis, ten patients (four M/six F) had PVA and 38 patients (five M/33 F) had SVA, with a median age of 54 and 33 years, respectively (p<0.05). Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both PVA and SVA patients, as was their response to gluten-free diet. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy. CONCLUSION: PVA was observed in 21% of patients with ACD. Except for their older age at diagnosis, patients with PVA presented with similar clinical, biological and immune characteristics and outcomes as did patients with SVA.
Adult celiac disease with severe or partial villous atrophy: A comparative study.
PMID: 18359595  Mar 2008
 
CONCLUSIONS: We have shown that a transglutaminase antibody level can be defined which gives a positive predictive value of 100% for coeliac disease. From published data, these observations can be extended to most second-generation transglutaminase antibody kits. Our data provide further evidence that diagnostic guidelines could be modified so that small bowel biopsy is no longer regarded as mandatory in patients with such high transglutaminase antibody levels. This will avoid an invasive procedure and lead to a more rapid diagnosis and earlier treatment for over half of the new patients with coeliac disease.
Coeliac disease: a biopsy is not always necessary for diagnosis.
PMID: 18194500  April  2008
 
Serum antibodies levels correlated very well with the severe histological alterations (TVA), but the correlation is not so good with SVA and PVA.
Serological and histological correlations in celiac disease.  
PMID:18333359  2007
 
RESULTS: DQ2/DQ8 were more frequent in female than in male patients (94% F, 85% M; P= 1.6 x 10(-3)) with a 99.1% and 90.5% calculated negative predictive value of the HLA test, respectively. Surprisingly, the majority of the 39 DQ2/DQ8 negative cases were male.
HLA-DQ and Susceptibility to Celiac Disease: Evidence for Gender Differences and Parent-of-Origin Effects.
PMID: 18177450  Jan 2008
 
CONCLUSION: A substantial proportion of patients with true CD are EMA negative. This has implications for the pathogenesis of the disease. It also limits the value of EMA as a screening test, particularly in older adults and cigarette smokers.
Determinants of endomysial antibody status in untreated coeliac disease.
PMID: 17873614  Oct 2007

Our study clearly revealed that over-reliance on standard histological findings results in failure to diagnose celiac disease.
PMID: 17487584  May 2007


Should Stored Serum of Patients Previously Tested for Celiac Disease Serology be Retested for Transglutaminase Antibodies?
PMID: 17016136 Oct 2006

 


Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.  PMID: 16571636 Mar 2006


CONCLUSIONS: Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.
Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study. PMID: 16036509 May 2005


Among 115 adults with biopsy-proven celiac disease who fulfilled strict criteria, including serologic testing at the time of diagnosis and response to a gluten-free diet, 71% had total villous atrophy and 29% partial villous atrophy. Endomysial antibody was positive in 77% of those with total villous atrophy, compared to 33% with partial villous atrophy (P < 0.001) Seronegative celiac disease occurs. Endomysial antibody positivity correlates with more severe villous atrophy and not mode of presentation of celiac disease. Serologic tests, in clinical practice, lack the sensitivity reported in the literature.
Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy.PMID: 15185855 April 2004


EmA-negative coeliac disease is common. Reliance on EmA testing to select patients for biopsy will result in significant underdiagnosis.
Reliance on serum endomysial antibody testing underestimates the true prevalence of coeliac disease by one fifth. PMID: 10720117


At this time small bowel biopsy seems to be the only correct procedure to diagnose a case of suspected celiac disease, especially in patients with mild symptoms or suspected for celiac disease, because they belong to high-risk groups.
Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease. PMID: 11374690


Low specificity of anti-tissue transglutaminase antibodies in patients with primary biliary cirrhosis. PMID: 16960894 Sept 2006


Accuracy of Testing for Antibodies to Synthetic Gliadin-Related Peptides in Celiac Disease.
PMID: 16860613  July 2006


Anti-tissue transglutaminase IgA antibodies in peripheral neuropathy and motor neuronopathy.
PMID: 16774628  July 2006


Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside.
PMID: 16766047  June 2006


Antibody to Tissue Transglutaminase May Fall Short for Accurate Triage of Celiac Disease Medscape Nov 2004

The positive predictive value of IgA anti-tTG was 90% and the negative predictive value, 98%. In comparison, results for IgA EMA were 100% and 97%, IgA AGA 94% and 90%, and IgG AGA 70% and 98%, respectively.
Diagnosing celiac disease: a comparison of human tissue transglutaminase antibodies with antigliadin and antiendomysium antibodies. PMID: 15184223 June 2004

The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet.
Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies. PMID: 1303650

Serological markers detect asymptomatic coeliac disease among first-degree relatives of patients with sprue. However, some relatives with coeliac disease-related antibodies have 'normal' jejunal mucosa by conventional histology. Our study shows quantitative histological evidence that relatives of probands with positive coeliac disease-related serology are not false-positives, and that they should be considered as individuals with latent coeliac sprue.
Serological markers identify histologically latent coeliac disease among first-degree relatives. PMID: 8900904

 


Using tTGA as a single test in screening may result in missing up to 60-70% of celiacs with mild mucosal abnormalities. Combination with other screening tests (at least with AGA) is essential and strongly recommended.
Autoantibodies and Histogenesis of Celiac Disease PMID: 12853995

Anti-endomysium and anti-tissue transglutaminase antibodies are both highly efficient for routine laboratory screening: the choice of one or the other will depend on the available facilities. However, neither can replace intestinal biopsy for general population screening because, in this case, their respective positive predictive values are only 15.7% and 21.8%. During follow-up, anti-gliadin retain their value as an early predictor of gluten ingestion.
Serological markers for coeliac disease: is it time to change? PMID: 11529655

There is an association between IgA deficiency and low/negative EmA/AGA. Routine measurement of total serum IgA in patients suspected of having coeliac disease, either with EmA or where AGA is low, improves selection of patients for small bowel biopsy.
Association between serum levels of total IgA and IgA class endomysial and antigliadin antibodies: implications for coeliac disease screening.
PMID: 9222726

Although the ELISA tTGA assay is more convenient than EmA testing, it offers no advantages in sensitivity or specificity if used in isolation. However, incomplete concordance between EmA and tTGA positivity means that combination screening with both assays offers higher sensitivity, as almost a third of patients have only one antibody. As some coeliac patients with normal serum IgA are negative for both antibodies, biopsies should still be performed in seronegative individuals deemed at high risk for coeliac disease.
Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody positive and negative coeliac disease. PMID: 11346205

IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.
Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency. PMID: 14570724

In conclusion, AEM-negative CD is common and detection is only modestly enhanced by testing for IgA anti-tTG antibodies. Duodenal biopsy is still recommended for the accurate diagnosis of CD.
Anti-endomysial antibody negative celiac disease: does additional serological testing help? PMID: 11270789

While the tTG assay may be a useful predictor of celiac disease, small intestinal biopsy is still required to confirm the diagnosis. In clinical practice, even strongly positive tTG results are not specific in individual patients, do not necessarily correlate with the degree of severity of biopsy change and, as a result, are also unlikely to be useful for monitoring diet compliance.
Strongly positive tissue transglutaminase antibody assays without celiac disease. PMID: 14760428


CONCLUSIONS: IgA TTGA and EMA levels correlate with duodenal villous atrophy in pediatric CD patients. IgA TTGA >100 or EMA >1:1280 were nearly always associated with CD histopathology. With further validation of this observation, strongly positive titers might be considered sufficient for diagnosis of pediatric patients at risk for CD.
Correlation of Duodenal Histology With Tissue Transglutaminase and Endomysial Antibody Levels in Pediatric Celiac Disease.
PMID: 17428743   April 2007


Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations?
PMID:15867045 Pediatrics. 2005 May;115(5):1341-6.

Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy. PMID: 15654798 Jan 2005

Symptoms disappeared after GFD in patients suspected to have celiac disease but with slight histologic lesions. Although Marsh I-II lesions cannot be classified as celiac lesions (ESPGAN criteria), the patients' symptoms at presentation and the clear improvement of symptoms when on GFD, with or without improvement of histologic lesions, supports the assumption that these patients are sensitive to gluten and may justify treatment with a GFD.
The symptomatic and histologic response to a gluten-free diet in patients with borderline enteropathy. PMID: 12488700

In the present study we demonstrated that a gluten challenge might be useful in identifying patients as being sensitive to gluten if initial small intestinal biopsies reveal only minor abnormalities.
Gluten challenge in borderline gluten-sensitive enteropathy. PMID: 11374684

Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.
Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal? PMID: 14674666

Anti-tTG does not seem effective to assess histologic recovery in the follow-up of celiac patients after they have started GFD due to its poor correlation with histologic damage.
Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease. PMID:14564185

EmA is a poor predictor of persisting VA after patients have started gluten-free diet, although it may be of value in monitoring dietary compliance.
Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery. PMID: 10710062

Endoscopic markers have disappointing sensitivity even in a population at high risk of celiac disease, particularly for partial VA. As celiac disease is an important cause of dyspepsia, consideration should be given to serological screening to further improve diagnosis rates, as few centers will have the resources to routinely biopsy all patients.
Disappointing sensitivity of endoscopic markers for villous atrophy in a high-risk population: implications for celiac disease diagnosis during routine endoscopy. PMID: 11467643

Our results suggest that serial testing with TGA and AEA might allow, in some cases, the avoidance of intestinal biopsy to confirm the diagnosis of CD.
Is intestinal biopsy always needed for diagnosis of celiac disease? PMID: 12818277

The counting of intraepithelial lymphocytes (IELs) in the villous tips of architecturally normal small bowel biopsy specimens was proposed as a method to measure mucosal infiltration in gluten sensitive patients. This is a very simple and sufficiently reliable method to count IELs. In patients with an architecturally normal duodenal mucosa, the IEL count in villous tips helps to distinguish between patients with PCD and non-coeliac controls.
Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? Aug 2004

Villous tip analysis seems to distinguish early coeliac from non-specific changes, thus providing a valuable tool in routine practice, especially when borderline findings are involved. Its value appears to be similar to counting of gammadelta+ cells, which, however, requires frozen biopsy samples.
Villous tip intraepithelial lymphocytes as markers of early-stage coeliac disease.
PMID: 15180179

 

         

 
When all is said and done, the best test may be one's response to the diet. An elimination diet may be very useful because frequently other food intolerances are involved. Nobody needs a doctors prescription or permission to make dietary changes. I believe it is a good idea to run the blood work in case an easy diagnosis can be had, and perhaps a biopsy even when blood tests are negative, but in the event the tests are negative or inconclusive~ consider a dietary trial.