Age related changes of soluble Fas, Fas ligand and Bcl-2 in autoimmune thyroid diseases
JK Mysliwiec, M Oklota, A Nikolajuk & M Gorska
Apoptosis plays a pivotal role in the regulation of the immune mechanisms in the pathogenesis of autoimmune thyroid diseases. The aim of the study was to compare soluble Fas, FasL and Bcl-2 in Graves disease (GD) and Hashimoto thyroiditis (HT) in relation to the age of the studied patients. The study was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on methimazol (euGD) 2/20 patients with hyperthyroid GD (hrGD) 3/15 patients with HT in euthyreosis on levothyroxine (euHT) 4/16 patients with hypothyroid Ht (hoHT) 5/12 healthy volunteers age and sex-matched to group 14. The serum levels of Fas, FasL, Bcl-2, aTPO and aTG were determined by the ELISA kit. aTSHR were measured by the RIA method. The statistical significance was estimated by the Mann-Whitney U-test. Spearmans test was performed to evaluate relationships between variables.
Level of sFas was the highest in hoHT individuals: 8.7 (7.29.8) ng/ml as compared to the controls: 6.6 (4.48.0) (P<0.01) and euHT patients: 7.7 (5.28.7) (P<0.05). We found positive correlations between sFas and age in GD patients (r=0.35, P<0.05). There were no significant differences in sFasL concentrations between studied groups of patients. However in GD patients we found a negative correlation between sFasL and age in all HT and GD patients (r=−0.34, P<0.01). Levels of sBcl-2 were significantly increased in euHT: 31.0 (13.544.1) ng/ml as compared to the controls: 8.0 (5.018.9) (P<0.05) and euGD patients: 9.1 (6.619.0) (P<0.05). We found a negative correlation between sBcl-2 and age in HT patients (r=−0.42, P<0.05).
In summary our results suggest that mechanisms of apoptosis mediated by interaction of Fas and its ligand play an important role in the active stage of the development of autoimmune process both in pathogenesis of Hashimoto thyroiditis and Graves disease. Fas/FasL and Bcl-2 signaling pathways seem to be age-related and may explain, at least in part, milder course of Graves disease in elderly patients and increased prevalence of Hashimoto disease in this group of subjects.