Endocrine Abstracts

Fc Receptor-like (FCRL) genes play a role in the immune system by encoding proteins that function as receptors on the surface of immune cells. Peripheral blood B cells, which are positive for FCRL3 and FCRL4, are rarely found in healthy individuals. In previous studies overexpression of FCRL4 was observed in patients with Graves’ disease (GD) but without association with thyroid peroxidase (TPOAb) or thyroglobulin (TgAb) antibodies. Nonetheless, the clinical significance of FCRLs expression in GD and Graves orbitopathy (GO) remains unclear. We decided to evaluate the expression of FCRL 2, 3, 4 mRNA in patients with GD and GO and its role in the development and severity of these diseases.

Methods: Peripheral blood samples from patients with GD (diagnosed on the basis of positive TSH receptor autoantibodies, TRAb; n=26) or GO (diagnosed on the basis of ophthalmic assessment and positive TRAb currently or in medical history; n=49) hospitalized in the Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, were collected. Healthy individuals without thyroid diseases served as Control (n=16). Expressions of FCRL2, FCRL3 and FCRL4 were measured by real-time PCR and analyzed using the 2^−ΔΔCT method.

Results: FCRL3 mRNA expression was higher in peripheral blood from patients with GD comparing to GO (1.375 vs 0.673, P=0.004), as well as comparing specifically to active GO (1.375 vs 0.639, P=0.005). Regarding FCRL4 mRNA expression, even more pronounced increase was found in GD patients. Namely, FCRL4 mRNA expression was higher in GD comparing to Control (3.078 vs 0.916, P=0.003), comparing to GO (3.078 vs 1.178, P<0.001), comparing to active GO (3.078 vs 1.186, P=0.002) and comparing to inactive GO (3.078 vs 1.171, P=0.008). In turn, FCRL4 mRNA expression was higher in patients with hyperthyroidism (subclinical+overt) than in euthyroid patients (2.509 vs 0.995, P=0.001 when the whole group of individuals was considered; 2.509 vs 1.073, P=0.004 when GO+GD was considered). This positive association of FCRL4 mRNA expression with hyperthyroidism was confirmed in univariate regression analysis (OR=1.561, 95%CI=2.213, P=0.012). No clear relationship was observed between FCRL mRNA expression and thyroid antibodies (TRAb included). FCRL mRNA expression was not related to active/inactive GO.

Conclusion: The increased FCRL mRNA expression in patients with GD is associated with hyperthyroidism (but not with positive TRAb) and our study is the first one to confirm this relationship.