Aaron Lerner
AESKU.KIPP Institute, Germany
Title: New serological markers for celiac disease diagnosis: anti-neo-epitope human and microbial transglutaminases antibodies
Biography
Biography: Aaron Lerner
Abstract
The guidelines of ESPGHAN for the diagnosis of pediatric celiac disease (PCD) rely on anti-human tissue transglutaminase (tTg) as the prime and unique antibody for screening PCD population. Microbial Tg (mTg)is a family member of human tissue transglutaminase (tTg). Both enzymes,tTg and mTg,complexed to gliadin present neo-epitopes and antibodies against these complexes are called tTgneo-epitope andmTg neo-epitope. mTg is capable of cross-linking numerous molecules. Despite declarations of mTg safety, direct evidence for immunogenicity of the enzyme is lacking. The reliability of those antibodies in CD was evaluated.rnMaterials & Methods: The serological activity of mTg, tTg, mTg neo-epitope and tTg neo-epitope were studied in: 95 pediatric celiac patients (CD), 99 normal children (NC) and 79 normal adults (NA). Sera were tested by ELISAs, detecting IgA, IgG or both IgA and IgG: AESKULISA® tTg (tTg, RUO), AESKULISA® tTg New Generation (tTg neo-epitope (tTg-neo)), AESKULISA® mTg(RUO) and AESKULISA® mTg neo-epitope (mTg-neo, RUO). Marsh criteria were used for the degree of intestinal injury.rnResults: Comparing pediatric CD patients with the 2 normal groups: mTg-neo IgA, IgG and IgA+IgG antibody activities exceed the comparable mTg ones (p<0.0001). All mTg-neo and tTg-neo levels were higher (p<0.001). tTg IgA and IgG+IgA were higher than mTg IgA and IgA+IgG (p<0.0001). The levels of tTg-neo IgA/IgG were higher than tTg IgA/IgG (p<0.0001). The sequential antibody activities reflecting best the increased intestinal damage were: tTg-neo IgG ≥ mTg-neo IgG > mTg-neo IgA+IgG > tTg-neo IgA. Taken together, mTg-neo IgG and tTg-neo IgG correlated best with intestinal pathology (r2=0.989, r2=0.989, p<0.0001, p<0.0001, respectively).rnConclusion: mTg is immunogenic in children with CD and by complexing to gliadin its immunogenicity is enhanced. It represents a new serological marker for CD and matches the performance of the tTg neo-epitope. Both antibodies correlate with intestinal damage to the same degree. The neo-epitope tTg and mTg are new powerful serological markers for CD diagnosis. Further studies are needed to explore the pathogenic potential of those antibodies in CD.rn
