Distinct inflammatory gene expression in extraocular muscle and fat from patients with Graves’ orbitopathy

Abstract

Objective This study sought to compare patients with thyroid eye disease (TED) and normal controls with respect to the expression of the NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1 genes in orbital fat (OF) and extraocular muscle (EOM). Design and methods A prospective study design was used to evaluate 34 TED patients and 38 healthy controls. OF was harvested from 33 TED patients and 27 controls. EOM biopsies were obtained from 32 TED patients and 18 controls. Samples were examined by real-time PCR and evaluated using appropriate statistical analyses with a significance cut-off of P < 0.05. Results NR3C1 mRNA levels were higher in TED EOM (median 213 (96–376)) than those in control EOM (78 (34–138)) (P < 0.001), and NFKB expression was elevated in TED muscle (223 (31–520)) relative to that in control muscle (8 (6–31)) (P < 0.001). HSD11B1 expression was higher in TED EOM (0.78 (0.47–2.01)) than that in control EOM (0.22 (0.09–0.51)) (P < 0.001). Levels of CHUK, IKBKB, and FOS were higher in TED EOM (115 (20–223), 111 (54–299) and 0.11 (0.03–0.19), respectively) than those in control EOM (5.8 (2–13), 21 (5–52) and 0.05 (0.001–0.03) respectively) (P < 0.001). Conclusion Tissues involved in GO exhibited different mRNA levels of NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1. Gene expression in OF was similar for TED patients and controls. CHUK, IKBKB, FOS, NFKB, and HSD11B1 mRNA levels were higher in TED EOM than those in control EOM. NFKB was disproportionally elevated compared with NR3C1; this finding was indicative of a local proinflammatory profile.