Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation

Liver Int. 2008 Apr;28(4):467-76. doi: 10.1111/j.1478-3231.2008.01681.x.

Abstract

Background/aims: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end-stage autoimmune liver disease (ESALD), (ii) the correlation among auto-antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics.

Methods: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non-autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6-12 and > or = 24 months post-transplantation. Results were correlated with the HLA type of the recipient.

Results: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non-autoimmune) of the patients (five-fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA-DQ2 or HLA-DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post-transplantation. Post-transplantation, of the five patients with symptoms of 'classical' CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically 'silent' CD.

Conclusions: Patients with ESALD, especially those who are HLA-DQ2 or HLA-DQ8 positive had a high prevalence of CD-associated antibodies. Both tTGAs and EMAs decreased post-transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / mortality
  • Autoimmune Diseases / surgery
  • Biomarkers / analysis
  • Case-Control Studies
  • Celiac Disease / immunology*
  • Celiac Disease / mortality
  • Celiac Disease / pathology
  • Female
  • GTP-Binding Proteins / analysis
  • Graft Rejection
  • Graft Survival
  • HLA-DQ Antigens / analysis
  • Humans
  • Immunohistochemistry
  • Liver Failure / immunology*
  • Liver Failure / mortality
  • Liver Failure / surgery
  • Liver Transplantation / immunology*
  • Male
  • Middle Aged
  • Probability
  • Prognosis
  • Protein Glutamine gamma Glutamyltransferase 2
  • Reference Values
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Survival Analysis
  • Transglutaminases / analysis

Substances

  • Autoantibodies
  • Biomarkers
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins