Oversecretion of Soluble CTLA-4 in Various Autoimmune Diseases Overlapping Celiac Disease

Aim: To evaluate the levels of soluble CTLA-4 (sCTLA-4) in sera of celiac disease (CD) patients with overlapping autoimmune diseases (OAD; diabetes mellitus, autoimmune thyroid diseases, inflammatory bowel diseases, and autoimmune polyendocrine syndromes). Methods: Sera from Italian patients with CD were obtained and enzyme-linked immunosorbent assay was used to measure sCTLA-4. Results: Consistently high serum sCTLA-4 levels were observed in CD (13.20 ng/mL, p<0.0001) and OAD (19.48 ng/mL, p<0.0001) compared to normal controls. A significant increase in the level of serum sCTLA-4 was observed in OAD (p=0.0273) compared to CD alone. At variance, no significant difference in the sCTLA-4 levels was observed when single OAD were compared. Conclusion: The present study shows for the first time a statistically significant increase of serum sCTLA-4 levels in CD patients with associated autoimmune disease (namely, CD and OAD) versus patients with CD alone. Previously, the potential genetic associations of several CTLA-4 polymorphisms to susceptibility to autoimmune diseases have been described, although the relationship between CTLA-4 polymorphisms and the ability to produce the soluble form is not fully clarified. CTLA-4 is a strong actor in the adaptive response: our data give supportive evidence of the common background of autoimmune diseases.