Intestinal Transglutaminase Antibodies in Celiac Disease Diagnosis

NCT05810441 | Completed

• 1 other identifier: RC 04/19
• Study Type: observational
• Target: 213
• Locations: 1 country
• Sites: 1

Brief Summary

Celiac disease (CD) is a systemic autoimmune gluten-dependent enteropathy in subjects with HLA DQ2/8. CD prevalence is more than 1% with a progression to 2% in adulthood. Among the group at risk such as first-degree relatives, subjects with autoimmune diseases (eg type 1 diabetes) or with syndromes (Down's disease, Turner) the prevalence reaches 5-8%. Recently, in pediatrics CD diagnostic criteria have been modified and the intestinal biopsy can be omitted in presence of a specific clinical and laboratory picture. In the remaining pediatric cases and in all adult patients, the biopsy is fundamental for the diagnosis. The clinical manifestation of CD not always depends on the enteropathy and on the related symptoms, but it can be characterized by extra-intestinal symptoms (eg chronic fatigue, anemia, arthralgia, cerebellar ataxia, alterations of dental enamel) that often hamper a rapid CD recognition delaying the diagnosis especially in adults. Symptoms are not always related to intestinal injury and may be present even when intestinal mucosa is normal. This condition is known as potential CD in which serum IgA anti-transglutaminase antibodies (anti-ttg) are generally positive at low concentrations (eg higher 2-3 times than the cut-off) or positive occasionally. In this clinical context, the gluten-free diet is an effective therapy able to improve the clinical picture and to stop the anti-ttg production. Recent observations, especially in pediatric field, have shown that in potential CD the immunological analysis of intestinal biopsies is characterized by the presence of anti-ttg deposits in the intestinal mucosa which predict the development of intestinal atrophy in a time span of 3- 5 years. Furthermore, these deposits disappear with the diet-therapy. In pediatric field, the diagnostic specificity of mucosal anti-ttg (anti-ttg-m) is between 95-98%, while the sensitivity is 100%. In adults, anti-ttg-m show 100% sensitivity in typical celiac disease (characterized by high serum anti-ttg concentrations and intestinal mucosa atrophy), while no results are available about potential celiac disease. Moreover, in adults data about the specificity of anti-ttg-m in infectious, oncological and inflammatory diseases of the gastro-intestinal tract are not available. The main study objectives are to evaluate anti-ttg-m sensitivity in patients with typical celiac disease and anti-ttg-m specificity in patients with oncological and inflammatory bowel diseases.

Conditions

Celiac Disease

Keywords

Celiac disease,; Mucosal anti-ttg; Intestinal biopsy culture

Outcome Measures

Primary Outcomes (2)

• To evaluate the sensitivity of anti-ttg-m for the diagnosis of typical celiac disease in adult and pediatric subjects

  Anti-ttg-m will be evaluated using direct immunofluorescence and biopsy culture assays. For direct immunofluorescence technique: cryosections of intestinal tissue will be incubated with anti-ttg antibody labeled with rhodamine and subsequently with an antibody against human IgA conjugated with fluorescein. The cryosections will be analyzed with a fluorescence microscope equipped with a software to localize the overlap between red (rhodamine) and green (fluorescein) signals of the two antibodies. For intestinal biopsy culture: biopsies will be maintained in culture medium for 72 hours at 37 °C in the presence of soluble gliadin fragments. After 72 hours the culture liquid will be centrifuged and analyzed for the presence of anti-ttg and anti-endomysium by means of ELISA immuno-enzymatic technique and indirect immunofluorescence assay, respectively. Sensitivity will be evaluated in subjects with typical celiac disease

  At the time of intestinal biopsy

• To evaluate the specificity of anti-ttg-m in the control group

  Anti-ttg-m will be evaluated as described in Outcome 1. Evaluation of specificity will be carried out in subjects with inflammatory diseases (Crohn disease, ulcerative colitis, in acute phase or in remission) or with oncological pathology at gastro-intestinal level or with infectious disease (Helicobacter pylori) tested negative for serum anti-ttg

  At the time of intestinal biopsy

Secondary Outcomes (2)

• To compare immunofluorescence technique and biopsy culture assay in searching anti-ttg-m

  At the time of intestinal biopsy

• To demonstrate the gluten-dependence of anti-ttg-m in potential CD patients by searching anti-ttg-m after gluten-free diet

  After 12 months of gluten-free diet

Study Arms (3)

Typical celiac disease

* symptomatic subjects (gastro-intestinal or extra-intestinal symptoms) tested positive for serum anti-ttg concentrations and with pathological intestinal biopsy; * symptomatic and asymptomatic subjects at risk of CD (first-degree relatives of CD patients or subjects with autoimmune disorders) tested positive serum CD antibodies and with atrophic intestinal mucosa

Other: Evaluation of diagnostic accuracy of anti-ttg-m

Potential celiac disease

Symptomatic subjects tested positive for both serum CD antibodies and anti-ttg-m but with normal intestinal mucosa

Other: Evaluation of diagnostic accuracy of anti-ttg-m

Control group

Adult and pediatric subjects with inflammatory gastro-intestinal disorders (Crohn disease and ulcerative colitis in acute phase or in remission), oncologic diseases (tumors of the gastro intestinal tract) and infectious diseases (eg Helicobacter pylori gastritis) tested negative for serum anti-ttg

Other: Evaluation of diagnostic accuracy of anti-ttg-m

Interventions

Evaluation of diagnostic accuracy of anti-ttg-m OTHER

Mucosal anti-ttg evaluated in intestinal biopsy samples

Control group; Potential celiac disease; Typical celiac disease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric and adult subject. Subjects with clinical suspicion of CD; asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD; subjects undergoing gastro-intestinal endoscopy for infectious, oncologic or inflammatory disorders

You may qualify if:

• Pediatric and adult subjects
• Subjects with clinical suspicion of CD, positive serum anti-ttg concentrations with any value or type of presentation (permanent or fluctuating)
• Asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD (eg family members of CD patients, subjects with autoimmune diseases)
• Subjects undergoing gastro-intestinal endoscopy for infectious (eg Helicobacter pylori gastritis), oncologic (tumors of the gastro intestinal tract) or inflammatory disorders (Crohn disease, ulcerative colitis, eosinophilic esophagitis) in acute phase or in remission

You may not qualify if:

• Subjects in whom to take biopsies is not indicated during the gastro-intestinal endoscopy
• Subjects with oncological pathology undergoing chemotherapy treatment because anti-blastic agents may play an inhibitory activity in the production of immunoglobulins

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

IRCCS materno infantile Burlo Garofolo

Trieste, 34137, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Intestinal biopsy samples

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Chiara Zanchi, MD

  IRCCS materno infantile Burlo Garofolo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 12, 2023
• Study Start: September 23, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

IT (1)