ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P356 | DOI: 10.1530/endoabs.63.P356

Relationship among T- and B-lymphocytes of the peripheral blood and thyroid tissue in patients with Graves' disease

Margarita A Dudina1,2, Andrey A Savchenko1,3, Sergey A Dogadin1,2, Alexandr G Borisov1,3, Igor V Kudryavcev4,5, Anton V Moshev 3 & Vladimir A Man’kovsky2

1Krasnoyarsk State Medical University Named After Prof. V.F. Voino-Yasenetsky, Krasnoyarsk, Russian Federation; 2Krasnoyarsk State Regional Clinical Hospital, Krasnoyarsk, Russian Federation; 3Federal Research Center «Krasnoyarsk Science Center» of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of medical problems of the North, Krasnoyarsk, Russian Federation; 4Research Institute of Experimental Medicine, St. Petersburg, St. Petersburg, Russian Federation; 5Far Eastern Federal University, Vladivostok, Russian Federation.

The exact pathogenesis and causative interaction between T- and B-lymphocytes in peripheral blood and thyroid gland immune-mediated mechanisms of Graves disease (GD) are still unknown. Detailed knowledge about lymphocyte subpopulation composition in peripheral blood and thyroid tissue will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. Aim: to study the relationship between helper- (Th-cells), regulatory T-cells (Treg) and B lymphocyte composition of peripheral blood and thyroid tissue in patients with GD undergoing epifascial thyroidectomy.

Materials and methods: The study included 43 women with GD, mean age 39.95±14.38, who were performed the epifascial thyroidectomy and 67 healthy women were examined as a control. The median of thyroid stimulating hormone (TSH), autoantibodies to TSH receptor, free thyroxine and triiodothyronine level was respectively 0.08 (0.01; 0.58 mIU/L, 10.25 (6.85; 24.68) IU/ml, 16.89 (11.39; 31.5) and 5.93 (4.6; 7.7) nmol/ml. All women treated with Antithyroid drugs (ATDs) for at least 1 month before surgery. Phenotypic composition of Th-cells, Treg and B-lymphocytes were measured by flow cytometry, using direct immunofluorescence, respectively, of whole peripheral blood and lymphocytes isolated from thyroid tissue. Analysis of stained cells was performed on a flow cytometer FC-500 (Beckman Coulter, USA). Each sample was analyzed at least 50,000 lymphocytes.

Results: In peripheral blood of GD patients we revealed the positively interaction between the relative amount of B-lymphocytes with Treg and activated T-helper cells (r=+0.39, P=0.009), B2-cells and naïve B-lymphocytes with CD3+CD4+CD25+- (r=+0.49, P<0.001 and r=+0.42, P=0.003, respectively) and CD3+CD4+CD127LowCD25High-cells (r=+0.49, P<0.001 and r=0.37, P=0.012, respectively). In thyroid tissue the Treg is completely excluded from the system of interactions with activated B-lymphocytes. In thyroid tissue of GD patients the relative number of CD3+CD4+-cells interact with the level of CD19+CD5+CD23+-lymphocytes (r=+0.79, P=0.036) and the percentage number of CD3+CD4+CD25+-cells with CD19+CD23+- (r=+0.85, P=0.014), CD19+CD5-CD23+- (r=0.80, P=0.034), CD19+CD5+CD23+- (r=+0.93, P=0.025) and CD19+CD27+CD23+-lymphocytes (r=+0.82, P=0.023).

Conclusion: Emerging evidence suggests that ATDs may functionally hinder the proper development of autoimmune process and alter T- and B-cell interactions with antigen presenting cells in immunological synapse of thyroid gland in GD. Thus, this interaction contribute directly to the key mechanism underlying the development of organ-specific autoimmunity functioning in peripheral blood and that may associated with ATDs and their potential functional effects on thyroidal immune dysregulation.

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