Endocrine Abstracts

Objectives: The Clinical Activity Score (CAS) is used to measure and classify Graves orbitopathy activity (GO). However, CAS is partly subjective, and the evaluation of its components is binary. As CAS is known to be correlated with TSH receptor antibodies (TRAb), we wanted to evaluate other immunological parameters in the peripheral blood as markers of GO activity.

Methods: The study included 32 patients (19 females, 13 males). CAS was evaluated by a single experienced physician. Patients were not treated for GO, except by local measures. All patients were euthyroid on therapy. We measured TRAb, immunoglobulins, and B lymphocyte subpopulations. Multicolour flow cytometric analysis of B cell subsets was performed using the backbone of six monoclonal antibodies (anti-CD38, - CD27, -CD21, -CD19, -IgM, -IgG). This approach provided phenotypic characterization of naïve B cells, circulating marginal zone B cells (MZB), CD21^low B cells, class-switched B cells, transitional B cells and plasmablasts in peripheral blood. Ordinal regression was used for data analysis with CAS as a dependent variable.

Results: In the multivariate analysis, there was a positive association between CAS (1-4) and TRAb but a negative association between CAS and MZB and IgA.

Conclusions: Although this is just preliminary data from a small study, it seems that the activity of GO may be modulated by or associated with changes of some less often considered components of the immune system. While TRAb drives the inflammatory response and positively correlated with CAS, we found that IgA and the presence of MZB are associated with the less active form of GO. The role of MZB in autoimmunity is still unclear. However, it has been demonstrated that these cells may have a dual role in autoimmune pathophysiological processes. MZB may promote autoimmunity by rapid production of low-affinity antibodies with self-reactivity to clear pathogens and apoptotic cell debris. On the contrary, this subset of B cells may acquire a regulatory phenotype and produce IL-10 after activation of the TLR9 signal through direct contact with apoptotic cells. Our results indicate that the latter function of MZB may have implications in the pathogenesis of GO. The perplexing role of MZB in GO needs to be further investigated. Our findings may pave the new way to assess GO activity and opens new therapeutic options.