The Iceberg of Celiac Disease: What Is Below the Waterline?

Background & Aims: We explored the relationships between anti-tissue transglutaminase antibody and indirect measures of malabsorption and disease activity in people with undetected celiac disease. Methods: From the Cambridge General Practice Health Study, 7550 participants' serum samples were tested for antiendomysial antibody (EMA). The 87 samples positive for EMA were tested for human anti-tissue transglutaminase antibody (TGA). Multivariate linear regression was used to explore the relationship between TGA concentrations and various physiologic and anthropometric measures. Results: Among the 87 EMA-positive people, there were consistent relationships between increasing TGA levels and various physiologic and anthropometric measures. A 50% increase in the mean TGA level was associated with a 0.02 g/cm2 (95% confidence interval [CI], −0.03 to −0.009) lower mean hip bone mineral density, a 0.1 g/dL (95% CI, −0.17 to −0.01) lower mean hemoglobin, a 0.22 kg/m2 (95% CI, −0.46 to 0.03) lower mean body mass index, a 0.09 mmol/L (95% CI, −0.16 to −0.02) lower serum cholesterol, and a 0.1 mmol/L (95% CI, 0.04 to 0.16) higher random blood glucose concentration, independent of age, sex, and smoking habit. Conclusions: The relationships we found between concentrations of TGA and various physiologic and anthropometric variables suggest that in reality, celiac disease is a continuum with a variable degree of severity. Although clinically overt disease is defined by symptoms, signs, and small bowel histology, the severity of previously undetected disease variously labeled in the past as silent, potential, or latent could, instead, be estimated by the concentration of a detectable serum antibody.