Polymorphisms and expression of toll-like receptors in autoimmune thyroid diseases.

Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid diseases (AITDs). Prognosis of AITDs varies in each patient. Toll-like receptors (TLRs) are pattern-recognition receptors that activate signaling pathways involved in the production of proinflammatory cytokines. UNC93B1 is a transcription factor of TLR7 and TLR9. In this study, we examined the association of TLR expression and TLR and UNC93B1 polymorphisms with the development and prognosis of AITDs. The ratio of intracellular TLR7 (iTLR7) and iTLR9 intensities in B cells was lower in patients with GD in remission than in patients with intractable GD (p = 0.0007). The frequency of G allele of TLR7 rs3853839 G/C polymorphism was significantly higher in male patients with GD and intractable GD than in control subjects (p = 0.0062 and 0.0173, respectively). The frequencies of T allele of TLR9 rs187084 C/T polymorphism and C allele of TLR9 rs352140 C/T polymorphism were significantly higher in patients with intractable GD who had GG genotype of TLR7 rs3853839 polymorphism, which is associated with higher TLR7 expression, than in patients with GD in remission (p = 0.0334 and 0.0023, respectively). The frequencies of AA genotype and A allele of UNC93B1 rs308328 polymorphism were significantly higher in patients with GD than in patients with HD (p = 0.0406 and 0.0316, respectively). These results suggested that the ratio of iTLR7 and iTLR9 intensities was associated with the development and intractability of GD and that TLR7 and UNC93B1 polymorphisms were associated with the development of GD.