Proteomics: a Tool for Better Understanding of Celiac Disease

Background and aims: Celiac disease (CD) is a small intestine autoimmune disorder trigger by the ingestion of gluten containing cereals (wheat, barley and rye) in genetically predispose individuals (HLA-DQ2 or DQ8). The disease course with malabsorption, diarrhea, fail in child growth and extra intestinal manifestation such as ataxia, bone diseases, heart diseases, skin diseases. In addition, the diagnosis is based on the study of villous atrophy together with the titre of the antibodies against transglutaminase 2 (TG2), anti deamideated gliadine antibodies and endomysium antibodies (EMA) in both serum and duodenal biopsy of the expected person. On the other hand, proteomic analysis of the serum samples gives an idea regarding diagnosis and the treatment of this disease as well as the development of new markers. We aim to find out the difference between two methods of protein depletion in order to find more proteins and more reliable results during proteomic analysis of CD samples. Moreover, we aim to setup a protocol to study the circulating proteins in the blood of CD patients in order to better understand the diseases pathogenesis. Methods: Samples from celiac patients’ serum during active disease, same patients’ serum after one year of gluten free diet and healthy donors were prepared for proteomic analysis. We used 10 samples in each group. The majority of proteins were depleted by two different methods (A and B) while separated by isoelectric focusing and 2-D gel electrophoresis and identified by Malditof-tof. Results: The spots found by using method A were 348 while in method B, the amount was considerably increased to 689. Method B was selected for further analysis and statistically significant proteins were found. Some proteins were up or downregulated in celiac disease patients compared with the other groups. Conclusions: We setup a suitable protocol for the proteomic analysis of serum samples derived from CD. Depletion of major proteins by method B compare to method A allows us to find more proteins and more reliable results. Most of the identified proteins were related to vascular damage, suggesting their participation in the angiogenesis defect during the disease. Hence, protein profile during active CD and GFD can help in the study of the pathogenesis of the disease.