title: Analysis of costimulatory molecules OX40/4-1BB (CD134/CD137) detection on chosen mononuclear cells in children and adolescents with Graves' disease during methimazole therapy.
abstract: 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.
authors.affiliation: 2nd Department of Children's Diseases, Medical University Bialystok, Poland. abossowski@hotmail.com
authors.forename: Artur
authors.initials: A
authors.lastname: Bossowski
authors.forename: Anna
authors.initials: A
authors.lastname: Stasiak-Barmuta
authors.forename: Mirosława
authors.initials: M
authors.lastname: Urban
authors.forename: Anna
authors.initials: A
authors.lastname: Bossowska
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D013956:Antithyroid Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology; D016466:CHO Cells; D002648:Child; D006224:Cricetinae; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008713:Methimazole / Q000627:therapeutic use*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D053278:OX40 Ligand; D048069:Tumor Necrosis Factors / Q000097:blood*
chemical_list: D013956:Antithyroid Agents; D001323:Autoantibodies; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D048069:Tumor Necrosis Factors; D008713:Methimazole