Analysis of Costimulatory Molecules OX40/4-1BB (CD134/CD137) Detection on Chosen Mononuclear Cells in Children and Adolescents with Graves' Disease During Methimazole Therapy

• Published in: Journal of Pediatric Endocrinology and Metabolism Vol. 18; no. 12; pp. 1365 - 1372
• Main Authors: Bossowski, A., Stasiak-Barmuta, A., Urban, M., Bossowska, A.
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.01.2005
• Subjects: Adolescent; Adult; Animals; Antithyroid Agents - therapeutic use; Autoantibodies - immunology; Child; CHO Cells; Cricetinae; Female; Flow Cytometry; Graves Disease - blood; Graves Disease - drug therapy; Humans; Immunophenotyping; Male; Membrane Glycoproteins - blood; Methimazole - therapeutic use; Monocytes - immunology; Monocytes - metabolism; OX40 Ligand; Tumor Necrosis Factors - blood
• ISSN: 0334-018X; 2191-0251
• DOI: 10.1515/JPEM.2005.18.12.1365

Antibody synthesis follows interactions between the T cell receptor (TCR) on activated T lymphocytes and the main histocompatibility complex (MHC) present on APC cells, resulting in lymphocyte proliferation, as well as cytokine synthesis and release. The involvement of costimulatory markers OX40/4-1BB/4-1BBL leads to the enhancement of signals which are necessary for lymphocyte activation in addition to the antigen-specific signal and may prevent anergy. The aim of this study was to estimate the expression of OX40 and 4-1BB molecules on peripheral blood cells in patients with Graves' disease (GD) (n = 35, mean age 16.5 +/- 6.1 years) and non-toxic nodular goiter (NTNG) (n = 35, mean age 16.2 +/- 4.7 years), in comparison with sex- and age-matched healthy controls (n = 35, mean age 16.2 +/- 2.1 years). Expression of the costimulatory molecules on mononuclear cells was analyzed by three-color flow cytometry using a Coulter EPICS XL cytometer. Stimulating and blocking antibodies to the TSH-receptor using JPO9 CHO cells in unfractionated serum were measured by a highly sensitive commercial radioimmunoassay. The analysis of OX40/4-1BB expression in patients with newly recognized Graves' disease revealed a statistically significant increase in the percentage of CD134+ T cells (7% vs 1.4%, p <0.001) and CD137+ T cells (3.2% vs 0.8%, p <0.04) compared to the control group. After 2-6 months of methimazole therapy, the percentage of these cells in the peripheral blood of hyperthyroid patients returned to normal values. In addition, the expression of 4-1BBL (CD137L) was detected only on the surface of active monocytes in patients with untreated GD (3.8%), while in the group with nodular goiter and controls the values were trace (0.6% and 0.2%, respectively). We conclude that the changes of expression of costimulatory molecules on the surface of peripheral blood T cells and their significant relationship with the level of antithyroid antibodies indicate an involvement of these molecules in the pathogenesis of Graves' disease. A marked increase in the percentage of CD134/ CD137+ T cells at disease onset may indicate the need for more aggressive therapy in Graves' disease and for a greater duration than the standard 3-year period.