Altered expression profile of BAFF receptors on peripheral blood B lymphocytes in Graves’ Disease

Abstract

Background: B lymphocyte activating factor (BAFF) is a growth factor regulating B lymphocytes survival and maturation. Serum BAFF levels were elevated in patients affected with autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). The aim of this study is to investigate the association of expression of BAFF receptors on the peripheral blood B lymphocytes in addition to serum BAFF concentrations in patients affected with GD.Methods: Fifty-two GD patients, 39 Hashimoto’s thyroiditis (HT) patients and 23 healthy controls (HC) were recruited in this study. Serum BAFF levels and its receptors expression, including BAFF receptor 3 (BR3) and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), in AITD patients were compared to those in HC. In 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy, effects of steroids on serum BAFF levels and expression of BR3 and TACI were observed.Results: Serum BAFF levels were significantly elevated from 0.93 ± 0.24 ng/ml in HC to 1.18 ± 0.33 ng/ml in GD ( P =0.0027) and 1.02 ± 0.24 ng/ml in HT ( P =0.0331). BR3 expression on peripheral B lymphocytes were elevated in GD (mean MFI: 4.52 ± 2.06 in GD vs 3.00 ± 0.87 in HC, P =0.0015), while TACI expression on peripheral B lymphocytes were decreased in GD without significance (mean MFI: 7.96 ± 4.06 in GD vs 9.10 ± 3.37 in HC, P =0.1285). Expression of BR3 and TACI was not changed significantly in HT patients. Steroids significantly suppressed serum BAFF concentrations (from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P =0.0364) and BR3 expression in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P =0.0083). Conclusions: Altered expression of BAFF and its receptor may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy to treat GD.

Graves’ disease: introducing new genetic and epigenetic contributors

“…Similarly, the association of rs9514828 and rs4000607 in UK patients with GD have been reported that can change the gene expression (Lane et al 2019). As an underlying molecular mechanism, Wang et al showed that the skewed expression profile of BAFF receptors on B lymphocytes may mediate autoimmunity in GD, suggesting that restoring the normal expression profile can be a new strategy for GD treatment (Wang et al 2020). In other words, blocking the interaction of BAFF with its receptor negatively affects B-cell proliferation, indirectly decreasing B-cell survival and reducing the production of autoantibodies in GD (Lane et al 2020).…”