Celiac disease-associated transglutaminase autoantibody target domains at diagnosis are age and sex dependent

The contribution of age and/or sex to the transglutaminase (tTG) autoantibody response in celiac disease (CD) is not known. To gain insights into transglutaminase humoral autoimmunity at CD diagnosis, our aim was to characterize the autoimmune response against three tTG constructs [(full-length tTG(a.a.1-687), tTG(a.a.227-687), and tTG(a.a.473-687)] and to investigate into its relationship with CD patients' age and sex. One hundred seventy-five newly diagnosed CD patients (115 females and 60 males), subdivided into different groups according to age and sex, were studied using a serum 35S-radioimmunoassay. We found that among full-length tTG autoantibody-positive CD subjects (175/175), 50.9% (89/175) and 83.4% (146/175) had autoantibodies against tTG(227-687) and tTG(473-687) domains, respectively. Female patients of less than 4 years expressed tTG(227-687)Abs in significantly higher percentage and mean autoantibody titers vs. all other groups investigated, and tTG(473-687)Abs in significantly higher titers with respect to adult female patients. Our data identify a subset of CD patients showing a strong humoral tTG immunoreactivity at diagnosis, thus suggesting that age and sex influence the anti-tTG autoantibody response.