Circulating Anti–Galectin–1 Antibodies Are Associated With the Severity of Ocular Disease in Autoimmune and Infectious Uveitis

Abstract

Purpose: : Recent evidence indicates that galectin–1 (Gal–1), an endogenous lectin found at sites of immune privilege, plays critical roles on immunoregulation. Therapeutic administration of Gal–1 or its genetic delivery suppresses inflammation in experimental models of autoimmunity including arthritis and uveitis. However, the impact of Gal–1 in chronic inflammation has not yet been explored in clinical settings. To investigate the occurrence of circulating anti–Gal–1 antibodies in patients with autoimmune and infectious uveitis as potential determinant factors of disease progression.

Methods: : IgG, IgE and IgA anti–Gal–1 antibodies were assessed by ELISA and Western blot in sera from patients with autoimmune (n=47) and infectious (n=15) uveitis compared to healthy controls (n=30). The frequency of anti–Gal–1 antibodies was examined in patients experiencing progressive or benign evolution. The ability of anti–Gal–1 antibodies to recognize retinal tissue was assessed by ELISA, Western blot and immunohistochemistry following elution of specific antibodies from nitrocellulose filters previously adsorbed with recombinant Gal–1 and further incubated with patient sera.

Results: : IgE, IgG and IgA anti–Gal–1 antibodies were increased in sera from patients with autoimmune uveitis (p<0.001 vs controls), and in toxoplasmic retinochoroiditis (p< 0.001). The frequency of anti–Gal–1 IgE and IgG antibodies was associated with progressive disease and poor outcome in autoimmune and infectious uveitis. Furthermore, anti–Gal–1 antibodies strongly immunoreacted with retinal cell lysates and recognized several retinal structures mainly photoreceptors and pigment epithelium in retinal sections.

Conclusions: : Anti–retinal Gal–1 antibodies are associated with the progression of ocular disease, suggesting their potential use for the follow–up of patients with uveitis.

Keywords: uveitis-clinical/animal model • uvea • autoimmune disease