<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02242123</url>
  </required_header>
  <id_info>
    <org_study_id>ACPM05</org_study_id>
    <nct_id>NCT02242123</nct_id>
  </id_info>
  <brief_title>Celiac Disease Diagnosis in Patients With Weakly Positive Serum Anti-Transglutaminase: Duodenal Anti-Endomysium Assay.</brief_title>
  <official_title>Antiendomysium Antibodies Assay in the Culture Medium of Intestinal Mucosa: an Accurate Method for Celiac Disease Diagnosis in Patients With Weakly Positive Serum Anti-transglutaminase Antibodies.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Palermo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Palermo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Celiac disease (CD) is a chronic immune-mediated disorder that occurs in genetically&#xD;
      predisposed populations. Patients affected by the disease may be asymptomatic or manifest&#xD;
      classic malabsorption symptoms of diarrhea, steatorrhea, abdominal pain, and weight loss&#xD;
      after gluten ingestion (and related derivatives found in other grains). Diagnosis and&#xD;
      screening begin with the use of serologic tests, i.e. IgA anti-tissue transglutaminase (tTG)&#xD;
      and IgA anti-endomysial antibodies (EmA). Duodenal biopsy, still considered by many as the&#xD;
      criterion necessary for diagnosis, demonstrates the pathologic findings of small intestinal&#xD;
      villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis that occur on exposure&#xD;
      to dietary gluten. Genetic tests, revealing permissive haplotypes, may be helpful in&#xD;
      identifying susceptible individuals. CD diagnosis is still anchored to the criteria&#xD;
      established by the European Society of Pediatric Gastroenterology Hepatology and Nutrition in&#xD;
      1990. These require the mandatory presence of (a) villous atrophy with crypt hyperplasia and&#xD;
      increased intraepithelial lymphocytes (IELs) count when the patient is eating gluten, and (b)&#xD;
      a full clinical remission after elimination of gluten from the diet. As a consequence,&#xD;
      patients with minimal or no intestinal histology lesions pose a considerable problem, as&#xD;
      serum anti-tTG and EmA are known to be often negative, or weakly positive, in patients with&#xD;
      CD with mild intestinal damage. The investigators, in 2002, measured anti-tTG antibody in the&#xD;
      culture medium of intestinal biopsy specimens from patients with suspected CD and evaluated&#xD;
      the relationship between antibody production and severity of intestinal mucosal damage, and&#xD;
      demonstrated that anti-tTG assay of the culture medium of biopsy specimens can improve the&#xD;
      accuracy of CD diagnosis in patients negative for serum antibodies. The same investigators,&#xD;
      in 2011, evaluated the diagnostic accuracy of EmA assay in the culture medium of intestinal&#xD;
      biopsies for CD diagnosis and demonstrated that EmA assay in the culture medium had a higher&#xD;
      sensitivity and specificity than serum EmA and anti-tTG assay. The present study is performed&#xD;
      to investigate the clinical usefulness of the in vitro production of EmA in CD diagnosis in a&#xD;
      large number of consecutive adult patients with suspected CD and weakly positive [e.g. 2-3xN]&#xD;
      serum anti-tTG.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Celiac disease (CD) is a chronic immune-mediated disorder that occurs in genetically&#xD;
      predisposed populations. Patients affected by the disease may be asymptomatic or manifest&#xD;
      classic malabsorption symptoms of diarrhea, steatorrhea, abdominal pain, and weight loss&#xD;
      after gluten ingestion (and related derivatives found in other grains). The astute clinician&#xD;
      must be aware of a more subtle GI picture, as well as non-GI signs and symptoms (e.g.,&#xD;
      iron-deficiency anemia, abnormal liver function tests, and type 1 diabetes mellitus).&#xD;
      Diagnosis and screening begin with the use of serologic tests, i.e. immunoglobulin A (IgA)&#xD;
      anti-tissue transglutaminase (tTG) and IgA anti-endomysial antibodies (EmA). The EmA test is&#xD;
      performed by indirect immunofluorescence against reagent monkey esophagus or human umbilical&#xD;
      cord. The EmA bind to the smooth muscle antigen tTG, and the test result is reported as&#xD;
      titers. EmA are both moderately sensitive and highly specific (sensitivity 85%-98%,&#xD;
      specificity 97%-100%) for CD, but quickly become negative when the patient starts a&#xD;
      gluten-free diet. Anti-tTG is a highly sensitive and specific test for CD and is widely&#xD;
      available as an automated enzyme-linked immunosorbent assay from multiple manufacturers.&#xD;
      Although the sensitivity and specificity of this test is high, tTG can be present in as many&#xD;
      as 5% of control patients. In addition, false-positive tTG has been reported in patients with&#xD;
      Crohn's disease. Duodenal biopsy, still considered by many as the criterion necessary for&#xD;
      diagnosis, demonstrates the pathologic findings of small intestinal villous atrophy, crypt&#xD;
      hyperplasia, and intraepithelial lymphocytosis that occur on exposure to dietary gluten.&#xD;
      These changes exhibit improvement after withdrawal of gluten from the diet. Genetic tests,&#xD;
      revealing permissive haplotypes, may be helpful in identifying susceptible individuals.&#xD;
&#xD;
      CD diagnosis is still anchored to the criteria established by the European Society of&#xD;
      Pediatric Gastroenterology Hepatology and Nutrition in 1990. These require the mandatory&#xD;
      presence of (a) villous atrophy with crypt hyperplasia and increased intraepithelial&#xD;
      lymphocytes (IELs) count when the patient is eating gluten, and (b) a full clinical remission&#xD;
      after elimination of gluten from the diet. However, 20 years after those diagnostic criteria&#xD;
      were established, there is now growing evidence that at least two other factors must be&#xD;
      considered. First, symptomatic gluten sensitivity and malabsorption may coexist with a&#xD;
      normal-looking mucosa. Second, the finding of circulating IgA antibodies to tissue&#xD;
      transglutaminase (anti-tTG) or endomysium (EmA) at diagnosis is an extremely accurate&#xD;
      diagnostic instrument. As a consequence, CD diagnosis is nowadays also being done in&#xD;
      symptomatic patients presenting with a normal-looking mucosa but with a high titer of serum&#xD;
      EMA and/or anti-tTG antibodies. However, patients with minimal or no intestinal histology&#xD;
      lesions pose a considerable problem, as serum anti-tTG and EmA are known to be often&#xD;
      negative, or weakly positive, in patients with CD with mild intestinal damage.&#xD;
&#xD;
      Picarelli et al., in 1996, tried to establish whether the small intestine of CD patients is&#xD;
      the site of EmA production and whether gliadin challenge could induce their release. The&#xD;
      authors evaluated small intestine biopsy samples from treated and untreated CD patients and&#xD;
      controls, cultured in vitro for 24-48 h in the presence of gliadin. EmA were detected in the&#xD;
      supernatants of these organ culture biopsy samples by immunofluorescence technique and&#xD;
      enzyme-linked immunosorbent assay (ELISA), respectively. No EmA were found in the culture&#xD;
      supernatants of biopsy samples of controls, whereas they were detected in the culture&#xD;
      supernatants of all untreated CD patients, irrespective of gliadin challenge. Conversely, EmA&#xD;
      were not detected in supernatants of biopsy samples cultured in medium only from treated CD&#xD;
      patients, but were detected in the majority of the biopsy samples challenged with gliadin.&#xD;
&#xD;
      The investigators, in 2002, measured anti-tTG antibody in the culture medium of intestinal&#xD;
      biopsy specimens from patients with suspected CD and evaluated the relationship between&#xD;
      antibody production and severity of intestinal mucosal damage, and demonstrated that anti-tTG&#xD;
      assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in&#xD;
      patients negative for serum antibodies.&#xD;
&#xD;
      The same investigators, in 2011, evaluated the diagnostic accuracy of EmA assay in the&#xD;
      culture medium of intestinal biopsies for CD diagnosis and demonstrated that EmA assay in the&#xD;
      culture medium had a higher sensitivity and specificity than serum EmA and anti-tTG assay.&#xD;
      All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG carried&#xD;
      the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, a&#xD;
      subgroup of patients with negative-serum EmA/anti-tTG, normal villi architecture, and&#xD;
      positive-EmA in the culture medium, developed villous atrophy and underwent gluten-free diet,&#xD;
      with consequent resolution of the symptoms and complete intestinal histology recovery. The&#xD;
      investigators concluded that EmA assay in the culture medium should be included in the&#xD;
      diagnostic criteria for CD diagnosis in &quot;seronegative&quot; patients.&#xD;
&#xD;
      The present study is performed to investigate the clinical usefulness of the in vitro&#xD;
      production of EmA in CD diagnosis in a large number of consecutive adult patients with&#xD;
      suspected CD and weakly positive [e.g. normal value multiplied for 2-3 times, 2-3xN] serum&#xD;
      anti-tTG.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2012</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in the intestinal histology of the patients with clinically suspected CD and weakly positive [e.g. 2-3xN] serum anti-tTG antibodies, at the time of the first evaluation.</measure>
    <time_frame>At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.</time_frame>
    <description>Intestinal histology re-evaluation after at least one year after the first evaluation for suspected CD, without any dietary restriction. Marsh-Oberhuber's classification will be adopted: change from baseline (1st evaluation) to 2nd evaluation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum IgA anti-tTG antibodies evaluation.</measure>
    <time_frame>At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.</time_frame>
    <description>Evaluation of changes in serum levels of IgA anti-tTG antibodies after at least one year since the first evaluation for suspected CD, without any dietary restriction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms/signs evaluation.</measure>
    <time_frame>At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.</time_frame>
    <description>The evaluation of changes in symptoms/signs will be made according to the score calculated on the basis of the Visual Analogue Scale after at least one year since the first evaluation for suspected CD, without any dietary restriction.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>EmA assay in duodenal biopsies evaluation.</measure>
    <time_frame>At the time of first duodenal histology evaluation.</time_frame>
    <description>EmA assay in the culture medium of duodenal biopsies will be performed in all the patients, both Study and Control group, at the time of the first duodenal histology evaluation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Human leukocyte antigen (HLA) evaluation.</measure>
    <time_frame>At baseline (first visit).</time_frame>
    <description>All the patients will undergo human leucocyte antigen (HLA) typing for DQ2 and DQ8 alleles determination.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Celiac Disease</condition>
  <arm_group>
    <arm_group_label>Study group</arm_group_label>
    <description>Symptomatic patients, with weakly positive serum anti-tTG and evidence of mild intestinal histology damage (grade 1-2) at first evaluation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>Symptomatic patients, with weakly positive serum anti-tTG and evidence of intestinal villous atrophy (intestinal histology damage grade 3) at first evaluation.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Duodenal biopsy specimens&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study will include consecutive patients, referred to two centers in Palermo and&#xD;
        Sciacca, at the Internal Medicine Department of the University Hospital of Palermo, and at&#xD;
        the Internal Medicine Department of the Hospital of Sciacca (Agrigento), between January&#xD;
        2014 and June 2016.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. adult patients, both genders, aged between 18-70 years;&#xD;
&#xD;
          2. with suspected CD (i.e. affected with one or more of the following symptoms: chronic&#xD;
             diarrhea or constipation, alternating bowel habits, abdominal pain, dyspepsia,&#xD;
             recurrent aphthosis, dental enamel defects, thyroiditis, dermatitis, osteoporosis,&#xD;
             joints pain, weight loss, anemia, cryptogenetic hypertransaminasemia);&#xD;
&#xD;
          3. with weakly positive [e.g. 2-3xN] serum anti-tTG antibodies; and d) subjects with a&#xD;
             family history of CD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - patients with IgA deficiency, type 1 diabetes, inflammatory bowel diseases (Crohn's&#xD;
        disease or ulcerative colitis), Helicobacter pylori infection and other gastrointestinal&#xD;
        infection, and pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antonio Carroccio, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Internal Medicine Department of the Hospital of Sciacca (Agrigento)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Internal Medicine Department of the Hospital of Sciacca (Agrigento)</name>
      <address>
        <city>Sciacca</city>
        <state>Agrigento</state>
        <zip>92019</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine Department of the University Hospital of Palermo</name>
      <address>
        <city>Palermo</city>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Picarelli A, Maiuri L, Frate A, Greco M, Auricchio S, Londei M. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet. 1996 Oct 19;348(9034):1065-7. doi: 10.1016/S0140-6736(96)03060-7.</citation>
    <PMID>8874458</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, Iacono G, D'Amico D, Cavataio F, Teresi S, Caruso C, Di PL, Colombo A, D'Arpa F, Florena A, Notarbartolo A, Montalto G. Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis. Scand J Gastroenterol. 2002 Jan;37(1):32-8. doi: 10.1080/003655202753387329.</citation>
    <PMID>11843032</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, Iacono G, Di Prima L, Pirrone G, Cavataio F, Ambrosiano G, Sciume C, Geraci G, Florena A, Teresi S, Barbaria F, Pepe I, Campisi G, Mansueto P, Soresi M, Di Fede G. Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis. Eur J Gastroenterol Hepatol. 2011 Nov;23(11):1018-23. doi: 10.1097/MEG.0b013e328349b8a5.</citation>
    <PMID>21885984</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, Di Prima L, Pirrone G, Scalici C, Florena AM, Gasparin M, Tolazzi G, Gucciardi A, Sciume C, Iacono G. Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis. Clin Chem. 2006 Jun;52(6):1175-80. doi: 10.1373/clinchem.2005.061366. Epub 2006 Mar 30.</citation>
    <PMID>16574764</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>October 7, 2020</last_update_submitted>
  <last_update_submitted_qc>October 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Palermo</investigator_affiliation>
    <investigator_full_name>Pasquale Mansueto</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Celiac Disease</keyword>
  <keyword>Gluten-free diet</keyword>
  <keyword>EmA assay</keyword>
  <keyword>Duodenal culture medium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celiac Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02242123
org study id: ACPM05
nct id: NCT02242123
lead sponsor: 
has dmc: No
Celiac disease (CD) is a chronic immune-mediated disorder that occurs in genetically
      predisposed populations. Patients affected by the disease may be asymptomatic or manifest
      classic malabsorption symptoms of diarrhea, steatorrhea, abdominal pain, and weight loss
      after gluten ingestion (and related derivatives found in other grains). Diagnosis and
      screening begin with the use of serologic tests, i.e. IgA anti-tissue transglutaminase (tTG)
      and IgA anti-endomysial antibodies (EmA). Duodenal biopsy, still considered by many as the
      criterion necessary for diagnosis, demonstrates the pathologic findings of small intestinal
      villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis that occur on exposure
      to dietary gluten. Genetic tests, revealing permissive haplotypes, may be helpful in
      identifying susceptible individuals. CD diagnosis is still anchored to the criteria
      established by the European Society of Pediatric Gastroenterology Hepatology and Nutrition in
      1990. These require the mandatory presence of (a) villous atrophy with crypt hyperplasia and
      increased intraepithelial lymphocytes (IELs) count when the patient is eating gluten, and (b)
      a full clinical remission after elimination of gluten from the diet. As a consequence,
      patients with minimal or no intestinal histology lesions pose a considerable problem, as
      serum anti-tTG and EmA are known to be often negative, or weakly positive, in patients with
      CD with mild intestinal damage. The investigators, in 2002, measured anti-tTG antibody in the
      culture medium of intestinal biopsy specimens from patients with suspected CD and evaluated
      the relationship between antibody production and severity of intestinal mucosal damage, and
      demonstrated that anti-tTG assay of the culture medium of biopsy specimens can improve the
      accuracy of CD diagnosis in patients negative for serum antibodies. The same investigators,
      in 2011, evaluated the diagnostic accuracy of EmA assay in the culture medium of intestinal
      biopsies for CD diagnosis and demonstrated that EmA assay in the culture medium had a higher
      sensitivity and specificity than serum EmA and anti-tTG assay. The present study is performed
      to investigate the clinical usefulness of the in vitro production of EmA in CD diagnosis in a
      large number of consecutive adult patients with suspected CD and weakly positive [e.g. 2-3xN]
      serum anti-tTG.
Celiac disease (CD) is a chronic immune-mediated disorder that occurs in genetically
      predisposed populations. Patients affected by the disease may be asymptomatic or manifest
      classic malabsorption symptoms of diarrhea, steatorrhea, abdominal pain, and weight loss
      after gluten ingestion (and related derivatives found in other grains). The astute clinician
      must be aware of a more subtle GI picture, as well as non-GI signs and symptoms (e.g.,
      iron-deficiency anemia, abnormal liver function tests, and type 1 diabetes mellitus).
      Diagnosis and screening begin with the use of serologic tests, i.e. immunoglobulin A (IgA)
      anti-tissue transglutaminase (tTG) and IgA anti-endomysial antibodies (EmA). The EmA test is
      performed by indirect immunofluorescence against reagent monkey esophagus or human umbilical
      cord. The EmA bind to the smooth muscle antigen tTG, and the test result is reported as
      titers. EmA are both moderately sensitive and highly specific (sensitivity 85%-98%,
      specificity 97%-100%) for CD, but quickly become negative when the patient starts a
      gluten-free diet. Anti-tTG is a highly sensitive and specific test for CD and is widely
      available as an automated enzyme-linked immunosorbent assay from multiple manufacturers.
      Although the sensitivity and specificity of this test is high, tTG can be present in as many
      as 5% of control patients. In addition, false-positive tTG has been reported in patients with
      Crohn's disease. Duodenal biopsy, still considered by many as the criterion necessary for
      diagnosis, demonstrates the pathologic findings of small intestinal villous atrophy, crypt
      hyperplasia, and intraepithelial lymphocytosis that occur on exposure to dietary gluten.
      These changes exhibit improvement after withdrawal of gluten from the diet. Genetic tests,
      revealing permissive haplotypes, may be helpful in identifying susceptible individuals.

      CD diagnosis is still anchored to the criteria established by the European Society of
      Pediatric Gastroenterology Hepatology and Nutrition in 1990. These require the mandatory
      presence of (a) villous atrophy with crypt hyperplasia and increased intraepithelial
      lymphocytes (IELs) count when the patient is eating gluten, and (b) a full clinical remission
      after elimination of gluten from the diet. However, 20 years after those diagnostic criteria
      were established, there is now growing evidence that at least two other factors must be
      considered. First, symptomatic gluten sensitivity and malabsorption may coexist with a
      normal-looking mucosa. Second, the finding of circulating IgA antibodies to tissue
      transglutaminase (anti-tTG) or endomysium (EmA) at diagnosis is an extremely accurate
      diagnostic instrument. As a consequence, CD diagnosis is nowadays also being done in
      symptomatic patients presenting with a normal-looking mucosa but with a high titer of serum
      EMA and/or anti-tTG antibodies. However, patients with minimal or no intestinal histology
      lesions pose a considerable problem, as serum anti-tTG and EmA are known to be often
      negative, or weakly positive, in patients with CD with mild intestinal damage.

      Picarelli et al., in 1996, tried to establish whether the small intestine of CD patients is
      the site of EmA production and whether gliadin challenge could induce their release. The
      authors evaluated small intestine biopsy samples from treated and untreated CD patients and
      controls, cultured in vitro for 24-48 h in the presence of gliadin. EmA were detected in the
      supernatants of these organ culture biopsy samples by immunofluorescence technique and
      enzyme-linked immunosorbent assay (ELISA), respectively. No EmA were found in the culture
      supernatants of biopsy samples of controls, whereas they were detected in the culture
      supernatants of all untreated CD patients, irrespective of gliadin challenge. Conversely, EmA
      were not detected in supernatants of biopsy samples cultured in medium only from treated CD
      patients, but were detected in the majority of the biopsy samples challenged with gliadin.

      The investigators, in 2002, measured anti-tTG antibody in the culture medium of intestinal
      biopsy specimens from patients with suspected CD and evaluated the relationship between
      antibody production and severity of intestinal mucosal damage, and demonstrated that anti-tTG
      assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in
      patients negative for serum antibodies.

      The same investigators, in 2011, evaluated the diagnostic accuracy of EmA assay in the
      culture medium of intestinal biopsies for CD diagnosis and demonstrated that EmA assay in the
      culture medium had a higher sensitivity and specificity than serum EmA and anti-tTG assay.
      All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG carried
      the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, a
      subgroup of patients with negative-serum EmA/anti-tTG, normal villi architecture, and
      positive-EmA in the culture medium, developed villous atrophy and underwent gluten-free diet,
      with consequent resolution of the symptoms and complete intestinal histology recovery. The
      investigators concluded that EmA assay in the culture medium should be included in the
      diagnostic criteria for CD diagnosis in "seronegative" patients.

      The present study is performed to investigate the clinical usefulness of the in vitro
      production of EmA in CD diagnosis in a large number of consecutive adult patients with
      suspected CD and weakly positive [e.g. normal value multiplied for 2-3 times, 2-3xN] serum
      anti-tTG.
observational model: Case-Control
time perspective: Prospective
measure: Changes in the intestinal histology of the patients with clinically suspected CD and weakly positive [e.g. 2-3xN] serum anti-tTG antibodies, at the time of the first evaluation.
time frame: At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.
description: Intestinal histology re-evaluation after at least one year after the first evaluation for suspected CD, without any dietary restriction. Marsh-Oberhuber's classification will be adopted: change from baseline (1st evaluation) to 2nd evaluation
measure: Serum IgA anti-tTG antibodies evaluation.
time frame: At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.
description: Evaluation of changes in serum levels of IgA anti-tTG antibodies after at least one year since the first evaluation for suspected CD, without any dietary restriction.
measure: Symptoms/signs evaluation.
time frame: At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.
description: The evaluation of changes in symptoms/signs will be made according to the score calculated on the basis of the Visual Analogue Scale after at least one year since the first evaluation for suspected CD, without any dietary restriction.
measure: EmA assay in duodenal biopsies evaluation.
time frame: At the time of first duodenal histology evaluation.
description: EmA assay in the culture medium of duodenal biopsies will be performed in all the patients, both Study and Control group, at the time of the first duodenal histology evaluation.
measure: Human leukocyte antigen (HLA) evaluation.
time frame: At baseline (first visit).
description: All the patients will undergo human leucocyte antigen (HLA) typing for DQ2 and DQ8 alleles determination.
arm group label: Study group
description: Symptomatic patients, with weakly positive serum anti-tTG and evidence of mild intestinal histology damage (grade 1-2) at first evaluation.
arm group label: Control group
description: Symptomatic patients, with weakly positive serum anti-tTG and evidence of intestinal villous atrophy (intestinal histology damage grade 3) at first evaluation.
Duodenal biopsy specimens
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Antonio Carroccio, MD, PhD
role: Principal Investigator
affiliation: Internal Medicine Department of the Hospital of Sciacca (Agrigento)
facility: 
facility: 
country: Italy
citation: Picarelli A, Maiuri L, Frate A, Greco M, Auricchio S, Londei M. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet. 1996 Oct 19;348(9034):1065-7. doi: 10.1016/S0140-6736(96)03060-7.
PMID: 8874458
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PMID: 16574764
responsible party type: Principal Investigator
investigator affiliation: University of Palermo
investigator full name: Pasquale Mansueto
investigator title: Principal investigator
mesh term: Celiac Disease
sharing ipd: No