Cyclosporine-induced gingival overgrowth is associated to increased Transglutaminase -2 expression

Background. Cyclosporine A induced gingival overgrowth, which is characterized by an extracellular matrix increase, is due to an altered balance between collagen synthesis and degradation. Cyclosporine A is a potent immunosuppressant used to prevent organ transplant rejection and to treat various autoimmune diseases. Methods. This study proposed to verify if transglutaminase 2, an enzyme that is thought to be responsible for the assembling and remodeling of extracellular matrix, played some kind of role in the pathogenesis of the cyclosporine A-induced gingival overgrowth, its expression in the gingival overgrowth was compared to normal tissue to evidence any differences. Cyclosporine A-induced gingival overgrowth tissues were collected from 21 liver transplanted patients and case-controlled with 20 non-hyperplastic gingival biopsies from healthy patients who had had previous periodontal treatment. Both the presence and tissue distribution of transglutaminase 2 was determined in the two groups by immunohistochemistry and analysed in comparison to the tissue morphology and expression of lymphocyte related antigens (CD3 and CD20) and a vessel related marker (CD34). Results. A significant increase in the transglutaminase 2 expression was observed within the stromal component in the cyclosporine A treated patients compared to controls (p < 0.001). An increased transglutaminase 2 expression in mesenchymal cells and/or extracellular matrix in gingival overgrowth suggests that this molecule has a role in the pathogenesis of the disease. Further studies will investigate the therapeutic effect of antitransglutaminase 2 drugs (putrescine or 1,4-diaminobutane) in these patients.