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Research Supporting Diagnosis of Celiac Disease Without a Biopsy

2018:  Immunohistological analysis of the duodenal bulb: a new method for celiac disease diagnosis in children
2017:  Editorial:  The US Preventive Services Task Force Recommendation on Screening for Asymptomatic Celiac Disease:  A Dearth of Evidence  
The above editorial on the status of screening for Celiac Disease includes the following information.  Either:  
  1. combining the highly sensitive tTG-IgA with endomysial antibodies,
  2. very high titer tTG-IgA, or
  3. serially positive tTG by radioimmunoassay
results in a diagnostic accuracy that rivals that of traditional biopsy-based approaches.

Regarding (1) above:  In a study involving 1000 participants, parallel serologic testing and biopsies were undertaken in a random sampling of the general population, demonstrating very high accuracy (approximately 99%) for sequentially positive tTg-IgA and endomysial serology in predicting histologic changes of celiac disease. ​

Regarding (2) above:  The European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines for children have a nearly 100% positive predictive value for celiac disease when anti-tTG is 10 times the upper limit of normal or higher, regardless of symptom status.  

2017:  Coeliac disease: further evidence that biopsy is not always necessary for diagnosis.

2016:  Identification of a serum transglutaminase threshold value for the noninvasive diagnosis of symptomatic adult celiac       disease patients: a retrospective study.

2012:  European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease (see page 138 of article).

2015:  Are ESPGHAN "Biopsy-Sparing" Guidelines for Celiac Disease also Suitable for Asymptomatic Patients?

2014:  Letter regarding British Society of Gastroenterology guidelines on the diagnosis and management of coeliac disease

2014:  Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls

2013:  Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests
By comparing results of multiple blood tests with biopsies, the authors concluded that there is no single test, not even biopsy, that can conclusively diagnose or exclude CD in every individual.  Therefore, they propose a two-step diagnostic procedure: The first step is the combined blood test, with simultaneous determination of:
  • IgA anti-dpgli  (also known as Deaminated Gliadin Peptide Antibodies or DGP-IgA)
  • IgG anti-dpgli  (also known as DGP-IgG)
  • IgA anti-tTG and/or EMA
The vast majority of patients will have either three positive or three negative results, which will eliminate the need for a biopsy. The second step, jejunal biopsy, should be performed only in patients with discordant antibody results.   Note:  IgA-deficient CD patients were excluded from this study.

2016:  Decrease by 50% of plasma IgA tissue transglutaminase antibody concentrations within 2 months after start of gluten-free diet in children with celiac disease used as a confirming diagnostic test.

2014:  The presence of anti-endomysial antibodies and the level of anti-tissue transglutaminases can be used to diagnose adult coeliac disease without duodenal biopsy

2013:  Diagnosis of Celiac Disease in Adults Based on Serology Test Results, without Small-Bowel Biopsy

2010:  Celiac Disease Diagnosis: simple rules are better than complicated algorithms
This article by Dr. Fasano proposed that CD can be diagnosed if any 4 of these 5 criteria are satisfied: 
  • typical symptoms of celiac disease
  • positive serum celiac disease immunoglobulin A class autoantibodies at high titer 
  • human leukocyte antigen HLA-DQ2 or DQ8 genotypes
  • celiac enteropathy at the small bowel biopsy
  • response to the gluten-free diet 

2005:  Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations?

2013:  Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies

2010:  The Incidence and Cost of Unexpected Hospital Use After Scheduled Outpatient Endoscopy

2014:  New Test in Celiac Disease Provides Powerful Tool for Diagnosis and Immune Monitoring 
            The test is Nexvax2 Diagnostic.  It is not available, it is in development, progress shown on this page
            Science Daily article

2015  Another blood test to diagnose CD is also in development:  Science Daily article 
          Journal article:  Tetramer-visualized gluten-specific CD4+ T cells in blood as a potential diagnostic marker for coeliac disease without oral gluten challenge

2014:  Ex-vivo whole blood secretion of interferon (IFN)-γ and IFN-γ-inducible protein-10 measured by enzyme-linked immunosorbent assay are as sensitive as IFN-γ enzyme-linked immunospot for the detection of gluten-reactive T cells in human leucocyte antigen (HLA)-DQ2·5(+) -associated coeliac disease.

2007:  Hematologic manifestations of Celiac Disease
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