Endocrine Abstracts

Background and Aims: Relapse in Graves’ disease (GD) often occurs after antithyroid drugs (ATD) are withdrawn, however there is a lack of robust predictive biomarkers for relapse and little mechanistic insight into its pathophysiology. B-cell related cytokines and chemokines may reflect humoral immune activity and therefore be predictive of outcome. The purpose of this study was to evaluate serum B-cell activating factor (BAFF), Chemokine ligand 13 (CXCL13), A-proliferating inducing ligand (APRIL) and soluble B-cell maturation antigen (sBCMA) concentrations as prognostic markers for predicting relapse in GD.

Methods: This observational cohort study included 65 patients with GD who were followed-up for 12 months after ATD cessation. BAFF, CXCL13, APRIL and sBCMA were investigated when stopping ATD and 8-10 weeks later. Correlation between cytokine levels and the association with clinical outcome were analysed. Flow cytometry was used to investigate the association of cytokines and B cell subpopulations.

Results: In multivariate analysis, sBCMA at the end of ATD treatment was an independent prognostic factor for relapse (P=0.019; OR 1.03,95%CI 1.005-1.06) in GD patients after adjusting for age, sex, goitre, smoking status, and thyrotropin receptor antibody titre. sBCMA fell significantly after stopping ATD only in remission patients (P=0.004). BAFF was positively correlated to CXCL13 (P=0.02) and negatively correlated to sBCMA (P=0.02). There was a significant positive correlation between the frequencies of transitional B cells (CD19+CD24hiCD38hi) with sBCMA (P=0.02) and BAFF (P=0.02), and an inverse correlation between B regulatory cells (CD19+CD27+CD24hi) and BAFF (P=0.01).

Conclusions: BCMA is predominantly expressed on the plasma cell surface and shed sBCMA is a good surrogate marker for disease activity in systemic lupus erythematosus. sBCMA may also represent a prognostic biomarker for predicting relapse in GD that is independent of TRAb concentration. The association of sBCMA with the transitional B cell subpopulation may provide mechanistic insight into GD relapse.