FGFβ and TGFβ contribute to tissue remodeling, fibrosis and inflammation in the orbital tissue of severe Grav

Purpose To assess FGF-β, TGF-β, COX2 expression and immunocompetent cells in the orbital fat/connective tissue of patients with severe and mild Graves’ orbitopathy as possible prognosting factors of the course of disease. Methods Orbital tissue from 27 patients with GO undergoing orbital decompression (26 females and 1 male): 1) patients with severe GO (n = 18), the mean clinical activity score (CAS) was 8,5 (SD 2.5); 2) Patients with mild GO (n= 9), CAS was 2.2 (SD 0.8). 10 individuals undergoing blepharoplasty with no history of orbital inflammation served as controls. We evaluated the expression of CD4+, CD8+. CD20+, CD68 and FGF-β, TGF-β, COX2 in the orbital tissue by immunohistochemical staining Results The robust intraorbital CD4 + T cells infiltration in severe GO more than with mild GO with absence of CD20+ B lymphocytes and less CD8 infiltration were seen. CD68 expression (fibroblasts and macrophages staining) observed in the fibrous connective area of the adipose tissue of the mild GO and robust in severe GO. Increased FGFβ expression was observed in the fibroblasts and adipocytes in the connective tissue of the severe GO. The prominent TGFβ expression was observed in the fibrous connective tissue of the severe and mild GO. No expression of COX2 in the orbital tissue specimen was found in patients with GO. Conclusion Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGFβ and TGFβ expression may contribute to tissue remodeling, fibrosis and perpetuation of inflammation in the orbital tissue of GO especially in severe GO. Their high expression may suggest lack of effect of anti-inflammatory treatment.