Pretransplant positivity for circulating thyroid antibodies and graft survival in patients undergoing kidney transplant.

BACKGROUND: Thyroid disturbances are common in kidney graft recipients and they may influence graft function. CXC chemokine ligand 10 plays a role in both autoimmune thyroiditis and graft rejection. Thyroid antibody (Ab) positivity has been regarded as a marker of imbalance of the immune system. AIM: To relate pretransplant positivity for antithyroperoxidase (TPO) Ab and antithyroglobulin (Tg) Ab with kidney graft outcome. METHODS: Pretransplant thyroid antibodies were measured in 211 kidney graft recipients. RESULTS: The 5-year death-censored graft survival rate was 91.5%. Pretransplant circulating Tg Ab and TPO Ab were detected in 12 (5.7%) and 13 (6.2%) patients, respectively. Lifetime analysis showed similar 5-year graft survival rates in patients negative or positive for Tg Ab and TPO Ab (91.5 vs. 91.7% for Tg Ab and 91.9 vs. 84.6% for TPO Ab). However, patients with pretransplant positivity for TPO Ab showed a significantly lower 5-year graft survival when early graft loss (12 months after transplant) was excluded (84.6 and 96.8% for TPO Ab+ and TPO Ab- patients, respectively; p < 0.05). Occurrence of acute rejection and chronic allograft nephropathy was unrelated to thyroid Ab positivity. Serum CXC chemokine ligand 10 levels were similar independent of Tg Ab and TPO Ab positivity. CONCLUSION: Pretransplant positivity for TPO Ab may affect long-term graft survival in kidney graft recipients independent of occurrence of acute rejections and chronic allograft nephropathy.

Defect of a subpopulation of natural killer immune cells in Graves' disease and Hashimoto's thyroiditis: normalizing effect of dehydroepiandrosterone sulfate.

BACKGROUND: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves' disease (GD) and Hashimoto's thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. OBJECTIVE: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. DESIGN: We studied 13 patients with recent onset Graves' disease, 11 patients with Hashimoto's thyroiditis at first diagnosis and 15 age-matched healthy subjects. METHODS: NK cells were concentrated at a density of 7.75x10(6) cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16+/CD56+cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-beta (IFN-beta) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-alpha (TNF-alpha) from NK cells. RESULTS: Lower spontaneous, IL-2- and IFN-beta-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P<0.001). A decrease in spontaneous and IL-2-modulated TNF-alpha release from NK cells was also found in both groups of patients (P<0.001). The co-incubation of NK cells with IL-2/IFN-beta+DHEAS at different molar concentrations (from 10(-8) to 10(-5) M/ml/NK cells) promptly normalized NKCC and TNF-alpha secretion in GD and HT patients. CONCLUSIONS: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.