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Published in: BMC Endocrine Disorders 1/2021

Open Access 01-12-2021 | Hashimoto Thyroiditis | Research article

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

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

Published in: BMC Endocrine Disorders | Issue 1/2021

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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 explore the association of expression levels of BAFF and its receptors with AITD.

Methods

Fifty-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.

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.
Literature
1.
go back to reference Giuliani C, Cerrone D, Harii N, et al. A TSHR-LH/CGR chimera that measures functional thyroid-stimulating autoantibodies (TSAb) can predict remission or recurrence in Graves’ patients undergoing antithyroid drug (ATD) treatment. J Clin Endocrinol Metab. 2012;97:E1080–7.CrossRef Giuliani C, Cerrone D, Harii N, et al. A TSHR-LH/CGR chimera that measures functional thyroid-stimulating autoantibodies (TSAb) can predict remission or recurrence in Graves’ patients undergoing antithyroid drug (ATD) treatment. J Clin Endocrinol Metab. 2012;97:E1080–7.CrossRef
2.
go back to reference Seshasayee DVP, Yan M, Dixit Vm, Tumas D, Grewal I. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity. 2003;18:279–88.CrossRef Seshasayee DVP, Yan M, Dixit Vm, Tumas D, Grewal I. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity. 2003;18:279–88.CrossRef
3.
go back to reference Chang SE, Guo L, Tian J, et al. Autoimmune bone marrow environment severely inhibits B cell development by inducing extensive cell death and inhibiting proliferation. Autoimmunity. 2012;45:210–7.CrossRef Chang SE, Guo L, Tian J, et al. Autoimmune bone marrow environment severely inhibits B cell development by inducing extensive cell death and inhibiting proliferation. Autoimmunity. 2012;45:210–7.CrossRef
4.
5.
go back to reference Ferraccioli G, Gremese E. B cell activating factor (BAFF) and BAFF receptors: fakes and facts. Clinical Experimental Immunology. 2017;190:291–2.CrossRef Ferraccioli G, Gremese E. B cell activating factor (BAFF) and BAFF receptors: fakes and facts. Clinical Experimental Immunology. 2017;190:291–2.CrossRef
6.
go back to reference Migita K, Abiru S, Maeda Y, et al. Elevated serum BAFF levels in patients with autoimmune hepatitis. Hum Immunol. 2007;68:586–91.CrossRef Migita K, Abiru S, Maeda Y, et al. Elevated serum BAFF levels in patients with autoimmune hepatitis. Hum Immunol. 2007;68:586–91.CrossRef
7.
go back to reference Nocturne G, Mariette X. B cells in the pathogenesis of primary Sjogren syndrome. Nat Rev Rheumatol. 2018;14:133–45.CrossRef Nocturne G, Mariette X. B cells in the pathogenesis of primary Sjogren syndrome. Nat Rev Rheumatol. 2018;14:133–45.CrossRef
8.
go back to reference Lane LC, Allinson KR, Campbell K, et al. Analysis of BAFF gene polymorphisms in UK Graves’ disease patients. Clin Endocrinol. 2019;90:170–4.CrossRef Lane LC, Allinson KR, Campbell K, et al. Analysis of BAFF gene polymorphisms in UK Graves’ disease patients. Clin Endocrinol. 2019;90:170–4.CrossRef
9.
go back to reference Lin JD, Yang SF, Wang YH, et al. Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases. PLoS One. 2016;11:e015443671. Lin JD, Yang SF, Wang YH, et al. Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases. PLoS One. 2016;11:e015443671.
10.
go back to reference Fabris M, Grimaldi F, Villalta D, et al. BLyS and April serum levels in patients with autoimmune thyroid diseases. Autoimmun Rev. 2010;9:165–9.CrossRef Fabris M, Grimaldi F, Villalta D, et al. BLyS and April serum levels in patients with autoimmune thyroid diseases. Autoimmun Rev. 2010;9:165–9.CrossRef
11.
go back to reference Lin JD, Wang YH, Fang WF, et al. Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease. Clin Chim Acta. 2016;462:96–102.CrossRef Lin JD, Wang YH, Fang WF, et al. Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease. Clin Chim Acta. 2016;462:96–102.CrossRef
12.
go back to reference Vannucchi G, Covelli D, Curro N, et al. Serum BAFF concentrations in patients with Graves’ disease and orbitopathy before and after immunosuppressive therapy. J Clin Endocrinol Metab. 2012;97:E755–9.CrossRef Vannucchi G, Covelli D, Curro N, et al. Serum BAFF concentrations in patients with Graves’ disease and orbitopathy before and after immunosuppressive therapy. J Clin Endocrinol Metab. 2012;97:E755–9.CrossRef
13.
go back to reference Kajiyama Y, Kikuchi K, Takai A, et al. B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha. Clin Dev Immunol. 2012;2012:1–4.CrossRef Kajiyama Y, Kikuchi K, Takai A, et al. B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha. Clin Dev Immunol. 2012;2012:1–4.CrossRef
14.
go back to reference Gilbert JA, Kalled SL, Moorhead J, et al. Treatment of autoimmune hyperthyroidism in a murine model of Graves’ disease with tumor necrosis factor-family ligand inhibitors suggests a key role for B cell activating factor in disease pathology. Endocrinology. 2006;147:4561–8.CrossRef Gilbert JA, Kalled SL, Moorhead J, et al. Treatment of autoimmune hyperthyroidism in a murine model of Graves’ disease with tumor necrosis factor-family ligand inhibitors suggests a key role for B cell activating factor in disease pathology. Endocrinology. 2006;147:4561–8.CrossRef
15.
go back to reference Khan WN, Wright JA, Kleiman E, et al. B-lymphocyte tolerance and effector function in immunity and autoimmunity. Immunol Res. 2013;57:335–53.CrossRef Khan WN, Wright JA, Kleiman E, et al. B-lymphocyte tolerance and effector function in immunity and autoimmunity. Immunol Res. 2013;57:335–53.CrossRef
16.
go back to reference Saulep-Easton D, Vincent FB, Quah PS, et al. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells. Leukemia. 2016;30:163–72.CrossRef Saulep-Easton D, Vincent FB, Quah PS, et al. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells. Leukemia. 2016;30:163–72.CrossRef
17.
go back to reference Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, et al. (2016) Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, et al. (2016) Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus.
18.
go back to reference Pieper K, Grimbacher B, Eibel H. B-cell biology and development. J Allergy Clin Immunol. 2013;131:959–71.CrossRef Pieper K, Grimbacher B, Eibel H. B-cell biology and development. J Allergy Clin Immunol. 2013;131:959–71.CrossRef
19.
go back to reference Campi I, Tosi D, Rossi S, et al. B Cell Activating Factor (BAFF) and BAFF Receptor Expression in Autoimmune and Nonautoimmune Thyroid Diseases. Thyroid. 2015;25:1043–9.CrossRef Campi I, Tosi D, Rossi S, et al. B Cell Activating Factor (BAFF) and BAFF Receptor Expression in Autoimmune and Nonautoimmune Thyroid Diseases. Thyroid. 2015;25:1043–9.CrossRef
20.
go back to reference Ross DS, Burch HB, Cooper DS, et al. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26:1343–421.CrossRef Ross DS, Burch HB, Cooper DS, et al. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26:1343–421.CrossRef
21.
go back to reference Perros P, Hegedus L, Bartalena L, et al. Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement. Orphanet J Rare Dis. 2017;12:72.CrossRef Perros P, Hegedus L, Bartalena L, et al. Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement. Orphanet J Rare Dis. 2017;12:72.CrossRef
22.
go back to reference Zhu W, Ye L, Shen L, et al. A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with graves’ ophthalmopathy. J Clin Endocrinol Metab. 2014;99:1999–2007.CrossRef Zhu W, Ye L, Shen L, et al. A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with graves’ ophthalmopathy. J Clin Endocrinol Metab. 2014;99:1999–2007.CrossRef
23.
go back to reference Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, et al. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. 2016;25:582–92.CrossRef Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, et al. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. 2016;25:582–92.CrossRef
24.
go back to reference Hua C, Audo R, Yeremenko N, et al. A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells. J Autoimmun. 2016;73:64–72.CrossRef Hua C, Audo R, Yeremenko N, et al. A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells. J Autoimmun. 2016;73:64–72.CrossRef
25.
go back to reference Ji X, Wan J, Chen R, et al. Low frequency of IL-10-producing B cells and high density of ILC2s contribute to the pathological process in Graves’ disease, which may be related to elevated-TRAb levels. Autoimmunity. 2020;53:78–85.CrossRef Ji X, Wan J, Chen R, et al. Low frequency of IL-10-producing B cells and high density of ILC2s contribute to the pathological process in Graves’ disease, which may be related to elevated-TRAb levels. Autoimmunity. 2020;53:78–85.CrossRef
26.
go back to reference Vincent FB, Saulep-Easton D, Figgett WA, et al. The BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev. 2013;24:203–15.CrossRef Vincent FB, Saulep-Easton D, Figgett WA, et al. The BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev. 2013;24:203–15.CrossRef
27.
go back to reference Zhang Y, Li J, Zhang Y-M, et al. (2015) Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases. Journal of Immunology Research 2015:1–12. Zhang Y, Li J, Zhang Y-M, et al. (2015) Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases. Journal of Immunology Research 2015:1–12.
28.
go back to reference Wang Y, Li YJ, Jiang WQ, et al. Expression of BAFF-R, but not BAFF, is an independent prognostic factor in diffuse large B-cell lymphoma patients treated with R-CHOP. Ann Hematol. 2015;94:1865–73.CrossRef Wang Y, Li YJ, Jiang WQ, et al. Expression of BAFF-R, but not BAFF, is an independent prognostic factor in diffuse large B-cell lymphoma patients treated with R-CHOP. Ann Hematol. 2015;94:1865–73.CrossRef
Metadata
Title
Altered expression profile of BAFF receptors on peripheral blood B lymphocytes in Graves’ disease
Authors
Xin Wang
Jinhui Huang
Aixia Zhang
Chen Fang
Qi Ma
Pengjun Jiang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2021
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-021-00752-3

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