Possible reasons for different pattern disappearance of thyroglobulin and thyroid peroxidase autoantibodies in patients with differentiated thyroid carcinoma following total thyroidectomy and iodine-131 ablation.

The purpose of this study was to reveal some possible factors for the differences between the pattern of disappearance of thyroglobulin autoantibodies (anti-Tg) and thyroid peroxidase autoantibodies (anti-TPO) in patients with differentiated thyroid carcinoma following thyroidectomy and iodine-131 ablation. Patients with a history of follicular cell derived cancer (papillary, follicular, both papillary and follicular, Hürthle cell) and high pre-operative titers of anti-TPO and/or anti-Tg autoantibodies were retrospectively studied. Thyroglobulin (Tg) levels were measured using radio-immunometric assay (RIA). Anti-Tg and anti-TPO levels during the first 6 yr' follow-up were measured by passive agglutination, during the following 10 yr by ELISA method and during the last 2 yr by chemiluminescence assay. A statistically significant difference was observed between median time (72 months) of disappearance of anti-TPO and median time (39 months) of disappearance of anti-Tg in patients with complete ablation of thyroid tissue, following iodine-131 administration (p=0.0395, Logrank statistic=4.24, Kaplan-Meier method). A statistically significant difference was observed between median time (106 months) of disappearance of anti-TPO and median time (33 months) of disappearance of anti-Tg in patients >45 yr of age (p=0.034) and between median time (111 months) of disappearance of anti-TPO and median time (41 months) of disappearance of anti-Tg in patients with tumor size <2 cm (p=0.0175). We concluded that patients with differentiated thyroid carcinoma and pre-surgical elevated titers of both Tg and anti-TPO tend to become earlier anti-Tg seronegative. Although tumor size and age may influence the pattern of thyroid autoantibody reduction, the exact reasons for the different rhythm of autoantibodies decrease must further be evaluated.

TH2 lymphocytes secrete functional VIP upon antigen stimulation.

In addition to the peptidergic innervation, immune cells may also represent a source for VIP in the lymphoid organs. Previous studies reported increased VIP mRNA and protein expression in mitogen-stimulated B and T lymphocytes. To determine whether specific T cell subsets are responsible for VIP production, we derived TH1 and TH2 effector cell lines from T-cell receptor transgenic mice. TH1 and TH2 cells were stimulated with the specific (pigeon cytochrome C peptide) or nonspecific (ovalbumin) antigen presented by MHC class II compatible antigen-presenting cells. Upon stimulation with the specific antigen, TH2, but not TH1 cells express VIP mRNA and intracelllular VIP protein, as determined by Northern blots and FACS analysis. Supernatants harvested from antigen-stimulated TH2 cells contain secreted VIP, as determined by Elisa, and induce cAMP in HEK293 cells transfected with the specific VIP/PACAP receptor VPAC1. These results confirm that TH2, but not TH1 cells, express and secrete functional VIP following specific antigen stimulation. The release of VIP within the lymphoid microenvironment following antigenic stimulation provides a physiological basis for the immunoregulatory effects of VIP on neighboring immune cells, such as downregulation of macrophage activation, effects on lymphocyte migration, on antigen-induced T cell apoptosis, and on T cell differentiation.