title: Mucosal molecular pattern of tissue transglutaminase and interferon gamma in suspected seronegative celiac disease at marsh 1 and 0 stages.
abstract: OBJECTIVE
  In celiac disease (CD), there is increased mRNA coding for tissue transglutaminase (tTG) and interferon gamma (IFNα). In seronegative celiac patients, the mucosal immune complexes anti-tTG IgA/tTG are found. We assayed tTG- and IFNα-mRNA in the mucosa of patients with a clinical suspicion of seronegative CD and correlated the values with intraepithelial CD3 lymphocytes (IELs).
  
  
  METHODS
  Distal duodenum specimens from 67 patients were retrieved and re-evaluated for immunohistochemically proven CD3 IELs. Five 10 μm sections were used for the extraction and assay of tTG and IFNα coding mRNA levels using reverse transcriptase real-time polymerase chain reaction (RT-PCR). Samples from 15 seropositive CD patients and 15 healthy subjects were used as positive and negative controls. Results were expressed as fold-change.
  
  
  RESULTS
  Our series was divided into three groups based on IEL count: >25 (14 patients: group A), 15-25 (26 patients: group B), and 0-15 (27 patients: Group C). tTG-mRNA levels were (mean ± SD): CD = 9.8 ± 2.6; group A = 10.04 ± 4.7; group B = 4.99 ± 2.3; group C = 2.26 ± 0.8, controls = 1.04 ± 0.2 (CD = group A > group B > group C = controls). IFNα-mRNA levels were: CD = 13.4 ± 3.6; group A = 7.28 ± 3.6; group B = 4.45 ± 2.9; group C = 2.06 ± 1.21, controls = 1.04 ± 0.4.
  
  
  CONCLUSIONS
  Our results suggest that tTG- and IFNγmRNA levels are increased in both seropositive and potential seronegative patients with CD, showing a strong correlation with the CD3 IEL count at stage Marsh 1. An increase in both molecules is found even when IELs are in the range 15-25 (Marsh 0), suggesting the possibility of a "gray zone" inhabited by patients which should be closely followed up in gluten-related disorders.
authors.affiliation: Department of Emergency and Organ Transplantation, Gastroenterology Section, University of Bari, Bari, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ierardi
authors.forename: Annacinzia
authors.initials: A
authors.lastname: Amoruso
authors.forename: Floriana
authors.initials: F
authors.lastname: Giorgio
authors.forename: Mariabeatrice
authors.initials: M
authors.lastname: Principi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Losurdo
authors.forename: Domenico
authors.initials: D
authors.lastname: Piscitelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Buffelli
authors.forename: Maria G
authors.initials: MG
authors.lastname: Fiore
authors.forename: Antonio
authors.initials: A
authors.lastname: Mongelli
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Castellaneta
authors.forename: Antonio
authors.initials: A
authors.lastname: Giangaspero
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Francesco
authors.forename: Lucia
authors.initials: L
authors.lastname: Montenegro
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D001706:Biopsy; D002446:Celiac Disease / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D012333:RNA, Messenger; C049937:anti-IgA; D007371:Interferon-gamma; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins