By using the phage display libraries technique it is possible to investigate in vivo (intestinal biopsy) early antibody responses in autoimmune disease. In particularly, this technique demonstrated that the humoral response against tissue transglutaminase occurs at the intestinal mucosal level, and that the human VH5 gene is the commonly used variable region by the immune system of CD-patients to build the anti-tTG. This means that phage display libraries technique is able to measure the specificity of the autoimmune response against the tissue transglutaminase enzyme and perhaps against others auto-antigens (GAD, ICA, TPO, cardiac-antigens) in the CD patients. Phage display libraries allow us to measure the specific auto-antibodies at the production site, also in patients testing negative for anti-tTG in the serum and allow us to identify early CD patients before their seroconversion and the deterioration of their jejunal mucosa. Therefore, the intestinal mucosa production of IgA anti-tTG could be important in the diagnostic work-up of early-stage CD, when mucosal histology is not yet diagnostic.