Altered expression profile of BAFF receptors on peripheral blood B lymphocytes in Graves\u2019 disease

Xin Wang,Qi Ma,Aixia Zhang,Chen Fang,Jinhui Huang,Pengjun Jiang

doi:10.1186/s12902-021-00752-3

Abstract

BackgroundB 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 explore the association of expression levels of BAFF and its receptors with AITD.MethodsFifty-two GD patients, 39 Hashimoto’s thyroiditis (HT) patients and 23 healthy controls (HC) were recruited in this study. Serum BAFF levels were measured by ELISA. Expression of BAFF receptors, including BAFF receptor 3 (BR3) and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), on B lymphocytes were analyzed by flowcytometry. Effects of steroids on serum BAFF levels and expression of BR3 and TACI were also observed in 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy.ResultsSerum 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).ConclusionsAltered 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.

Highlights

B lymphocyte activating factor (BAFF) is a growth factor regulating B lymphocytes survival and maturation
Elevated serum BAFF levels in patients affected with autoimmune thyroid diseases (AITD) Serum BAFF levels were elevated in autoimmune diseases including Graves’ disease (GD) in previous studies
There was no difference in BAFF concentrations between euthyroid patients and hypothyroid patients in Hashimoto’s thyroiditis (HT) group

Summary

Introduction

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 production of autoantibodies is a result of aberrant activation of autoreactive B lymphocytes. In autoimmune diseases, the excess production of B cell activation factor (BAFF, known as B lymphocytes stimulator, Blys) supports the survival and activation of these defective autoreactive B lymphocytes [2, 3]. Because its ability to rescue low-affinity autoreactive transitional B lymphocytes at tolerance checkpoints and promote their maturation [2, 3], BAFF has long been linked to autoimmune diseases. Over expression of BAFF in mice induced a dramatic expansion of activated autoreactive B lymphocytes and autoantibody production [4]. Serum BAFF levels are elevated in autoimmune diseases including systemic lupus erythematosus (SLE) [5], autoimmune hepatitis [6] and primary Sjögren’s syndrome [7]

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