It was shown recently that orbital fibroblasts express intensively CD40 and its ligation stimulates proinflammatory cytokines, glicosoaminoglycans and PGE2 production. CD40/CD154 interaction in the pathogenesis of Graves orbitopathy (GO) is suggested an important pathway of T cells induced fibroblast activation and proliferation.
Aim: To assess the role of CD40/CD154 interaction in GO pathogenesis and to estimate usefulness of soluble CD40 (sCD40) and CD154 (sCD154) measurements as markers of GO activity.
Material and methods: Fifty-one individuals in 4 groups: 1/15 euthyroid patients with clinical symptoms of GO who underwent corticosteroid therapy consisting of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone (P) and teleradiotherapy (TR); 2/14 patients with hyperthyroid Graves disease (GDtox); 3/22 patients with GD in euthyreosis treated with methimazol (euGD); 4/10 healthy volunteers age and sex-matched to group 13. The serum samples were collected 24 h before MP, 24 h after MP, after TR and at the end of therapy. Serum CD40, CD154 and TPOab were determined by ELISA and TSHRab by RIA.
Results: Serum concentrations of CD40 (in pg/ml) and CD154 (in ng/ml) were increased in GO patients: 84.9 (74.793.9) and 4.0 (2.57.3) respectively in comparison to controls (P<0.001 and P<0.05 respectively). Serum CD154 in GO group was elevated as compared to both hyperthyroid and euthyroid GD without clinical ophthalmopathy (P<0.001 both). The sCD40/sCD154 quotient was significantly elevated during in nonrespondent GO patients after MP (P<0.05) and at the end of the study (P<0.01).
Summary: Our data suggest an important role of CD40/CD154 interaction in the pathogenesis of autoimmune process leading to inflammatory infiltration in Graves orbitopathy, however usefulness of sCD40 and sCD154 measurements in prediction of effects of GO treatment and its monitoring needs further investigations.
25 - 29 Apr 2009
European Society of Endocrinology