Background
Previous studies have demonstrated altered serum B lymphocyte activating factor (BAFF) level and expression of BAFF and BAFF receptor (BAFF-R) in thyroid infiltrating lymphocytes in Graves’ disease (GD) patients. The aim of the present study was to investigate expression of receptors for BAFF on the peripheral blood B lymphocytes in addition to serum BAFF concentrations.
Methods
Fifty-two GD patients and twenty-three healthy controls (HC) were recruited in this study. Serum BAFF concentrations were measure by ELISA. Expression of receptors for BAFF on peripheral blood B lymphocytes, including BAFF-R and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), was analyzed by flow cytometry. Serum BAFF levels, expression of BAFF-R and TACI on peripheral blood B lymphocytes were compared between GD and HC groups. Correlations between serum BAFF concentrations and thyroid function and thyrotropin receptor autoantibody (TRAb) titers were analyzed in GD patients. In 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy, effects of steroids on serum BAFF levels and expression of BAFF-R and TACI were observed.
Results
Serum BAFF levels were significantly higher in GD patients (1.18 ± 0.33 ng/ml) than those in HC (0.93 ± 0.24 ng/ml, P = 0.0011). In GD patients, serum BAFF levels correlated positively with free thyroxine concentrations (Spearman r = 0.2460, P = 0.0394), but not TRAb titers (P = 0.4734). BAFF-R 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 < 0.0001), while TACI expression on peripheral B lymphocytes were decreased in GD (mean MFI: 7.96 ± 4.06 in GD vs 9.10 ± 3.37 in HC, P = 0.0331). Steroids significantly suppressed serum BAFF concentrations ( from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P = 0.0364) and BAFF-R expression on peripheral blood B lymphocytes in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P = 0.0083). Change of TACI expression on B lymphocytes was not statistically significant after steroids therapy.
Conclusions
Skewed expression profile of receptors for BAFF on B lymphocytes may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy for treating and cueing GD.