Endocrine Abstracts

Background: Relapse rates in young people with Graves’ disease (GD) are around 75% after 2 years of antithyroid drugs (ATD). However, there is little mechanistic insight into the pathophysiology of relapse and a lack of robust predictive biomarkers. B cell subsets and related cytokines may reflect humoral immune activity, for which T cells have an important supporting role.

Aims: The purpose of this study was to evaluate T and B cell subpopulations, along with B-cell activating factor (BAFF) and soluble B-cell maturation antigen (sBCMA) concentrations as prognostic markers for predicting clinical response in young GD patients treated with ATD and the B-cell depleting agent, Rituximab (RTX).

Methods: Adjuvant RTX was administered with a 12-month course of ATD in 27 paediatric GD patients. Serum BAFF and sBCMA were investigated at baseline prior to RTX, and 12 months later. B and T lymphocyte subsets were evaluated in the 24 months following RTX. The relationship between cytokines and lymphocyte subpopulations were determined and the association with clinical outcome investigated.

Results: Disease relapse within 12 months after ATD withdrawal occurred in 14 (52%) patients. One year after RTX, BAFF and sBCMA levels had decreased from baseline (P=0.005, P=0.03, respectively), with a significant decline of BAFF observed only in relapse patients (P=0.005). At baseline, BAFF was negatively correlated with switched memory B cells (CD19+CD27+IgD-) (rs=-0.81, P=2.5 x 10-6). CD3+T cells increased following RTX (P=0.028). The baseline CD4/CD8 ratio was associated with relapse (P=0.04), which remained significant in multivariate analysis adjusted for age, gender and baseline TRAb titre (OR 2.04 95%CI 1.58-700; P=0.04). There was a significant increase in the CD4/CD8 ratio after ATD was stopped (P=0.03).

Conclusion: A greater decline in BAFF levels after RTX may indicate a poor clinical response in young people with GD. The negative association of BAFF with switched memory cells may provide mechanistic insight into GD relapse. An elevated CD4/CD8 ratio has been proposed as a marker of disease activity in paediatric GD, and in this study was found to be a prognostic biomarker, independent of TRAb titre.