Anti-Citrullinated Protein Antibodies (ACPA) are Present in Tear Fluid of Dry Eye Disease (DED) Patients: Diagnostic and Therapeutic Implications

Abstract

Purpose : It is known that DED is a localized autoimmune disease of the ocular surface. The cellular (T-cells and APCs) and molecular contributors (cytokines and chemokines) to inflammation have been relatively well characterized. The contribution of humoral immunity (autoantibodies) remain under researched. We determined autoantibodies in the tear fluid and their contribution to ocular surface disease.

Methods : Patients with DED were examined clinically (n=166 eyes). Ocular surface washings (OSW) and impression cytology (IC) was performed, and analyzed for presence of ACPA using commercially available ELISA kit. Immunostaining was performed for presence of citrullinated proteins, Fc receptors, plasma cells and IGG. Dot blot analysis was performed to detect specific ACPAs.

Results : ACPA was present in 60% eyes of DED patients. 81% of ACPA positive patients did not have corresponding ACPA antibodies in the serum. Impression cytology revealed presence of citrullinated proteins within neutrophils in Sjogrens disease patients. Neutrophils showed expression of FC receptors and plasma cells colocalized with IGG. Dot blot analysis showed presence of polyclonality. Antibodies to citrullinated proteins (vimentin, alpha-enolase, histone 3, histone 4 and fibrinogen) were detected. Immunoglobulin levels in OSW of DED patients was significantly increased. Patients with DED who had ACPA positive OSW had more severe ocular surface disease. In parallel laboratory experiments, application of ACPA to the murine corneas resulted in corneal epitheliopathy.

Conclusions : ACPA may be produced locally in the eye over the ocular surface and may contribute to ocular surface disease in patients with DED.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.