Mucosal molecular pattern of tissue transglutaminase and interferon gamma in suspected seronegative celiac disease at marsh 1 and 0 stages

Saudi J Gastroenterol. 2015 Nov-Dec;21(6):379-85. doi: 10.4103/1319-3767.167189.

Abstract

Background/aim: 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).

Materials and 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.

MeSH terms

  • Adult
  • Antibodies, Anti-Idiotypic / metabolism
  • Biopsy
  • Celiac Disease / blood
  • Celiac Disease / metabolism*
  • Celiac Disease / pathology
  • Duodenum / metabolism
  • Duodenum / pathology
  • Epithelial Cells / metabolism
  • Female
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Immunoglobulin A / metabolism
  • Immunohistochemistry
  • Interferon-gamma / metabolism*
  • Intestinal Mucosa / metabolism*
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Protein Glutamine gamma Glutamyltransferase 2
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction / methods
  • Retrospective Studies
  • Transglutaminases / metabolism*

Substances

  • Antibodies, Anti-Idiotypic
  • Immunoglobulin A
  • RNA, Messenger
  • anti-IgA
  • Interferon-gamma
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins