[Costimulatory molecule CD40 expression in thyroid tissue of Graves' disease patients and its immune pathogenetic significance].

Objective: To explore the expression of costimulatory molecule CD40 in thyroid tissue of Graves' disease patients and understand its immune pathogenetic significance.

Methods: From January 2008 to December 2011, 8 patients undergoing partial thyroidectomy for Graves' disease (n = 3) or non-toxic goiter (n = 5) at Affiliated Suzhou Hospital of Nanjing Medical University and Third Affiliated Hospital of Soochow University were enrolled. Using the method of immunohistochemistry, the expression of CD40 was detected in their thyroid tissues. Variation in CD40 expression on thyroid follicular (TFC) in primary cultures was analyzed in the absence (no stimulation group) or presence of inflammatory cytokines including interleukin interferon-γ (IFN-γ) (IFN-γ stimulation group), interferon-6 (IL-6) (IL-6 stimulation group)and tumor necrosis factor (TNF)-α (TNF-α stimulation group) with flow cytometry. IFN-γ-stimulated TFC were cultured with agonist CD40 monoclonal antibody (5C11) (IFN-γ + CD40 group) or isotypic mouse IgG (mIgG) antibody (IFN-γ + mIgG group). And the proliferation of TFC was assessed by 3-(4,5)-dimethyl-thiazolyl-3,5-di-phenytetrazoliumromide (MTT) assays for each donor. The production of free triiodothyronine (FT3) and free thyroxine (FT4) and the release of thyroglobulin (Tg) were measured with radioimmunoassays.

Results: The expression of CD40 on infiltrated lymphocytes and TFC were detected in Graves' disease but not in non-toxic goiter patient tissues. Compared with no stimulation group (23.7% ± 7.3%), the expression of CD40 on TFC increased in IFN-γ stimulation group (86.4% ± 4.6%), IL-6 stimulation group (90.0% ± 4.2%) and TNF-α stimulation group (87.3% ± 4.2%). Compared with the IFN-γ + mIgG group (0.75 ± 0.06), the TFC proliferation of IFN-γ + CD40 group (1.14 ± 0.14) significantly increased (P < 0.01). The levels of FT3, FT4 and Tg secretion of IFN-γ + CD40 group were (1.10 ± 0.15) pmol/L, (0.80 ± 0.14) pmol/L and (30.23 ± 1.60) µg/L respectively. They were all significantly increased compared with the IFN-γ + mIgG group, of which the FT3, FT4 and Tg production were (0.76 ± 0.07) pmol/L, (0.63 ± 0.09) pmol/L and (21.37 ± 3.22) µg/L respectively (all P < 0.05).

Conclusions: CD40 is abnormally expressed in thyroid tissue of Graves' disease patients. And its costimulatory signal may take part in the immunopathologic mechanism of Graves' disease.