Analysis of peripheral blood leukocytes in patients with cyclosporine A-induced gingival hyperplasia

Background: Gingival overgrowth is one of the major adverse effects of the immunosuppressive drug cyclosporine A (CsA). Although several studies have attempted to determine the immunological mechanisms of gingival hyperplasia (GO) due to CsA therapy, the pathogenesis remains unclear. In this study, the distribution of the peripheral blood leukocytes in a group of renal transplant patients undergoing CsA therapy was analyzed and possible correlations of periodontal and pharmacological variables to lymphocyte subpopulations, natural killer cells, and monocytes investigated. Methods: Thirty-six patients were classified into 2 groups of 18 each according to the degree of gingival overgrowth. The periodontal evaluation included plaque index (PI), gingival index (GI), gingival overgrowth (GO), calculus index (CI), and probing depth (PD). The pharmacological variables of current doses of the therapeutic serum levels of CsA were investigated. The peripheral blood leukocytes were studied by 2-color flow cytometric analysis using anti-human CD2, CD3, CD4, CD8, CD11b, CD11c, CD16, CD19, HLA-DR, and CD3+HLA-DR+ monoclonal antibodies. Results: Statistical evaluation revealed that none of the pharmacological variables varied between the 2 groups. Responders (GO >30%) had significantly higher GI, PD, and GO scores compared to nonresponders (GO ≤30%). Of the immunological parameters studied, only CD2 was higher in the responder group. None of the clinical parameters correlated to the immunological values. Conclusions: The results of this study may be useful in explaining the underlying mechanisms of drug-induced gingival overgrowth. Several previously unsuspected cells and accessory activation mechanisms for T lymphocytes could play a role in the pathogenesis.