Children with celiac disease and high tTGA are genetically and phenotypically different

World J Gastroenterol. 2013 Nov 7;19(41):7114-20. doi: 10.3748/wjg.v19.i41.7114.

Abstract

Aim: To investigate whether celiac disease (CD) patients with tissue-transglutaminase antibody (tTGA) ≥ 100 U/mL are different from patients with lower tTGA levels.

Methods: Biopsy-proven (Marsh III) pediatric CD patients (n = 116) were prospectively included between March 2009 and October 2012. The biopsies were evaluated by a single pathologist who was blinded to all of the patients' clinical data. The patients were distributed into 2 groups according to their tTGA level, which was measured using enzyme-linked immunoassay: tTGA ≥ 100 U/mL and tTGA < 100 U/mL. The patients'characteristics, symptoms, human leukocyte antigen (HLA) genotype and degree of histological involvement were compared between the 2 groups.

Results: A total of 34 (29.3%) children had tTGA values < 100 U/mL and 82 (70.7%) tTGA levels of ≥ 100 U/mL. Patients with high tTGA levels had lower average body weight-for-height standard deviation scores (SDS) than did patients with tTGA < 100 U/mL (-0.20 ± 1.19 SDS vs 0.23 ± 1.03 SDS, P = 0.025). In the low tTGA group, gastrointestinal symptoms were more common (97.1% vs 75.6%, P = 0.006). More specifically, abdominal pain (76.5% vs 51.2%; P = 0.012) and nausea (17.6% vs 3.7%, P = 0.018) were more frequent among patients with low tTGA. In contrast, patients with solely extraintestinal manifestations were only present in the high tTGA group (18.3%, P = 0.005). These patients more commonly presented with aphthous stomatitis (15.9% vs 0.0%, P = 0.010) and anemia (32.9% vs 11.8%, P = 0.019). In addition, when evaluating the number of CD-associated HLA-DQ heterodimers (HLA-DQ2.5, HLA-DQ2.2 and HLA-DQ8), patients with low tTGA levels more commonly had only 1 disease-associated heterodimer (61.8% vs 31.7%, P = 0.005), while patients with high tTGA more commonly had multiple heterodimers. Finally, patients with tTGA ≥ 100 U/mL more often had a Marsh IIIc lesion (73.2% vs 20.6%, P < 0.001) while in patients with low tTGA patchy lesions were more common (42.4% vs 6.8%, P < 0.001).

Conclusion: Patients with tTGA ≥ 100 U/mL show several signs of more advanced disease. They also carry a larger number of CD associated HLA-DQ heterodimers.

Keywords: Anti-tissue transglutaminase antibodies; Celiac disease; Human leukocyte antigen; Phenotype; Serology.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Age Factors
  • Asymptomatic Diseases
  • Autoantibodies / blood*
  • Biopsy
  • Celiac Disease / blood
  • Celiac Disease / complications
  • Celiac Disease / diagnosis
  • Celiac Disease / genetics*
  • Celiac Disease / immunology*
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Duodenum / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • GTP-Binding Proteins
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics*
  • HLA-DQ Antigens / genetics
  • Humans
  • Immunoglobulin A / blood*
  • Infant
  • Infant, Newborn
  • Male
  • Phenotype
  • Prospective Studies
  • Protein Glutamine gamma Glutamyltransferase 2
  • Severity of Illness Index
  • Transglutaminases / immunology*

Substances

  • Autoantibodies
  • HLA Antigens
  • HLA-DQ Antigens
  • Immunoglobulin A
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins