The Levels of Regulatory T Lymphocytes and B Cells in Patients with Graves' Disease after Thyroidectomy
https://doi.org/10.31550/1727-2378-2023-22-4-70-76
Abstract
Aim: To study the levels of regulatory T lymphocytes (Treg) and B-cells in peripheral blood in patients with Graves' disease in dynamics after thyroidectomy.
Design: Single center, observational, prospective, cohort, open, controlled study.
Materials and methods. The study included 96 patients with Graves' disease, mean age 42.86 ± 10.81 years. Clinical, hormonal and immunological examinations were performed against the background of persistent drug-induced euthyroidism, before surgery, and also 1, 3, and 6 months after thyroidectomy. The levels of Treg and B-cells in the blood was examined by flow cytometry using direct immunofluorescence and monoclonal antibodies. The level of antibodies to thyroid-stimulating hormone receptors (rTSH) was assessed by enzyme immunoassay. The control group consisted of 85 healthy women of the same age.
Results. In patients with Graves' disease in the dynamics of the postoperative period, there was a consistent statistically significant decrease in the titer of antibodies to rTSH: from 14.69 (8.67–19.81) to 0.81 (0.59–0.93) IU/l. The absolute amount of Treg in their blood was reduced relative to the control values already in the preoperative period and decreased even more at 6 months after thyroidectomy. The proportion of CD19+ CD5+ - and CD19+ CD5– -cells in the examined patients before surgery was significantly higher than in the control group. The content of CD19+ CD5+ cells decreased as early as 1 month after thyroidectomy and remained at the level of control values. The сontent of CD19+ CD27– -cells in patients with Graves' disease in the preoperative period was higher than in the control group, decreased to the control values 1 month after thyroidectomy and remained in this range until the end of the follow-up. The content of CD19+ CD27+ cells in patients before thyroidectomy was lower compare to control, in the period of 1–3 months it corresponded to the control values, but decreased again on the 6th month after surgery.
Conclusion. The reduction of Treg and B-memory cells in the peripheral blood in patients with Graves' disease six months after thyroidectomy remains of immunosuppressive regulatory mechanisms with an increase in the migration activity of immune cells for a long time.
About the Authors
M. A. DudinaRussian Federation
1 Partizan Zheleznyak Str., Krasnoyarsk, 660022; 3a Partizan Zheleznyak Str., Krasnoyarsk, 660022
S. A. Dogadin
Russian Federation
1 Partizan Zheleznyak Str., Krasnoyarsk, 660022; 3a Partizan Zheleznyak Str., Krasnoyarsk, 660022
A. A. Savchenko
Russian Federation
3g Partisan Zheleznyakov Str., Krasnoyarsk, 660022
V. D. Belenyuk
Russian Federation
3g Partisan Zheleznyakov Str., Krasnoyarsk, 660022
V. A. Mankovsky
Russian Federation
3a Partizan Zheleznyak Str., Krasnoyarsk, 660022
A. G. Borisov
Russian Federation
3g Partisan Zheleznyakov Str., Krasnoyarsk, 660022
References
1. Zhou F., Wang X., Wang L., Sun X. et al. Genetics, epigenetics, cellular immunology, and gut microbiota: emerging links with Graves' disease. Front. Cell Dev. Biol. 2022;9:794912. DOI: 10.3389/ fcell.2021.794912
2. Lang B.H.H., Woo Y.C., Chiu K.W.H. Two-year outcomes of single-session high- intensity focused ultrasound (HIFU) treatment in persistent or relapsed Graves'disease. Eur. Radiol. 2019;29(12):6690–8. DOI: 10.1007/s00330-019-06303-8
3. Cao Y., Zhao X., You R., Zhang Y. et al. CD11c+ B cells participate in the pathogenesis of Graves' disease by secreting thyroid autoantibodies and cytokines. Front. Immunol. 2022;13:836347. DOI: 10.3389/fimmu.2022.836347
4. Francis N., Francis T., Lazarus J.H., Okosieme O.E. Current controversies in the management of Graves' hyperthyroidism. Expert. Rev. Endocrinol. Metab. 2020;15(3):159–69. DOI: 10.1080/17446651.2020.1754192
5. Furmaniak J., Sanders J., Sanders P., Li Y. et al. TSH receptor specific monoclonal autoantibody K1-70TM targeting of the TSH receptor in subjects with Graves' disease and Graves' orbitopathy — results from a phase I clinical trial. Clin. Endocrinol. (Oxf). 2022;96(6):878–87. DOI: 10.1111/cen.14681
6. Ankudinov A.S., Kalyagin A.N., Muneer A.R., Vijayaraghavan G. L-thyroxine influence on lipid profile of patients with ischemic heart disease on the background of hypothyroidism. Siberian Medical Review. 2020;2:30–5. (in Russian). DOI: 10.20333/2500136-2020-2-30-35
7. Hamilton L.O.W., Lim A.E., Clark L.J. Total thyroidectomy for Graves' disease — what do our patients think? A qualitative cohort study to evaluate the surgical management of Graves' disease. Surgeon. 2020;18(4):193–6. DOI: 10.1016/j.surge.2019.09.005
8. Zhang X., Olsen N., Zheng S.G. The progress and prospect of regulatory T cells in autoimmune diseases. J. Autoimmun. 2020;111:102461. DOI: 10.1016/j.jaut.2020.102461
9. Lane L.C., Cheetham T.D., Perros P., Pearce S.H.S. New therapeutic horizons for Graves' hyperthyroidism. Endocr. Rev. 2020;41(6):873– 84. DOI: 10.1210/endrev/bnaa022
10. Bartalena L., Piantanida E., Gallo D., Ippolito S. et al. Management of Graves' hyperthyroidism: present and future. Expert. Rev. Endocrinol. Metab. 2022;17(2):153–66. DOI: 10.1080/17446651.2022.2052044
11. Kudryavtsev I.V., Subbotovskaya A.I. Application of six-color flow cytometric analysis for immune profile monitoring. Medical Immunology. 2015;17(1):19–26. (in Russian). DOI: 10.15789/1563-0625-2015-1-19-26
12. Sutherland D.R., Ortiz F., Quest G., Illingworth A. et al. High-sensitivity 5-, 6-, and 7-color PNH WBC assays for both Canto II and Navios platforms. Cytometry B Clin. Cytom. 2018;94(4):637–51. DOI: 10.1002/cyto.b.21626
13. Nalla P., Young S., Sanders J., Carter J. et al. Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves' disease. Clin. Endocrinol. (Oxf). 2019;90(2):369–74. DOI: 10.1111/cen.13908
14. El Kawkgi O.M., Ross D.S., Stan M.N. Comparison of long-term antithyroid drugs versus radioactive iodine or surgery for Graves' disease: a review of the literature. Clin. Endocrinol. (Oxf). 2021;95(1):3–12. DOI: 10.1111/cen.14374
15. Kahaly G.J., Diana T., Olivo P.D. TSH receptor antibodies: relevance & utility. Endocr. Pract. 2020;26(1):97–106. DOI: 10.4158/EP-2019- 0363
16. Maurer E., Maschuw K., Reuss A., Zieren H.U. et al. Total versus neartotal thyroidectomy in Graves disease: results of the randomized controlled multicenter TONIG-trial. Ann. Surg. 2019;270(5):755– 61. DOI: 10.1097/SLA.0000000000003528
17. Qin J., Zhou J., Fan C., Zhao N. et al. Increased circulating Th17 but decreased CD4+ Foxp3+ Treg and CD19+ CD1dhiCD5+ Breg subsets in new-onset Graves' disease. Biomed. Res. Int. 2017;2017:8431838. DOI: 10.1155/2017/8431838
18. Zhang R., Miao J., Zhu P. Regulatory T cell heterogeneity and therapy in autoimmune diseases. Autoimmun. Rev. 2021;20(5):102715. DOI: 10.1016/j.autrev.2020.102715
19. Liu H.Y., Shi Z.Y., Fan D., Zhang S.X. et al. Absolute reduction in peripheral regulatory T cells in patients with Graves' disease and post-treatment recovery. Mol. Immunol. 2022;144:49–57. DOI: 10.1016/j.molimm.2022.02.004
20. Dudina M.A., Dogadin S.A., Savchenko A.A., Belenyuk V.D. T-lymphocytes phenotypic composition of peripheral blood in patients with Graves’ disease undergoing conservative therapy with thiamazole. Problems of Endocrinology. 2021;67(6):39–49. (in Russian). DOI: 10.14341/probl12812
21. Segundo C., Rodríguez C., García-Poley A., Aguilar M. et al. Thyroidinfiltrating B lymphocytes in Graves' disease are related to marginal zone and memory B cell compartments. Thyroid. 2001;11(6):525– 30. DOI: 10.1089/105072501750302813
22. Morris G., Puri B.K., Olive L., Carvalho A.F. et al. Emerging role of innate B1 cells in the pathophysiology of autoimmune and neuroimmune diseases: association with inflammation, oxidative and nitrosative stress and autoimmune responses. Pharmacol. Res. 2019;148:104408. DOI: 10.1016/j.phrs.2019.104408
23. She Z., Li C., Wu F., Mao J. et al. The role of B1 cells in systemic lupus erythematosus. Front. Immunol. 2022;28(13):814857. DOI: 10.3389/fimmu.2022.814857
24. Smith M.J., Rihanek M., Coleman B.M., Gottlieb P.A. et al. Activation of thyroid antigen-reactive B cells in recent onset autoimmune thyroid disease patients. J. Autoimmun. 2018;89:82–9. DOI: 10.1016/j.jaut.2017.12.001
Review
For citations:
Dudina M.A., Dogadin S.A., Savchenko A.A., Belenyuk V.D., Mankovsky V.A., Borisov A.G. The Levels of Regulatory T Lymphocytes and B Cells in Patients with Graves' Disease after Thyroidectomy. Title. 2023;22(4):70-76. (In Russ.) https://doi.org/10.31550/1727-2378-2023-22-4-70-76