Functional Unit in Sjögren’s

Syndrome

Michael E. Stern and Stephen C. Pflugfelder

Abstract

SjšgrenÕs syndrome lacrimal keratoconjunctivitis is a chronic autoimmune disease that has a signiÞcant impact on the quality of patientÕs lives throughout the world. Current evidence suggests that dysfunction of the complex lacrimal function unit (LFU: cornea, conjunctiva, lacrimal glands, and meibomian glands) results in unstable tear Þlm and chronic inßammation. Inßammatory cell (e.g., CD4+ T cells) inÞltration, elevated pro-inßammatory cytokine levels, increased epithelial cell apoptosis, and diminished goblet cell numbers within the LFU, coupled with decreased tear production, are hallmark features of SjšgrenÕs syndrome. The inability of lacrimal glands to adequately respond to signals of ocular surface dryness, an early feature of SjšgrenÕs syndrome, is hypothesized to perpetuate chronic inßammation. The cycle of autoimmunity during SjšgrenÕs syndrome is simpliÞed into two main stages: (1) the afferent arm, in which desiccating stress on the ocular surface elicits the initial immune response and (2) an efferent arm, which describes activation and homing of autoreactive CD4+ T cells to the ocular surface that contribute to local tissue remodeling and destruction. Indeed, early inßammatory intervention can restore secretory function within the LFU; however, if left untreated, chronic inßammation may irreversibly impact the function of the lacrimal glands and/or conjunctival goblet cells. Current research is focused on gaining a better understanding of the mechanisms that contribute to the immunopathogenesis of SjšgrenÕs syndrome with the goals of developing sensitive diagnostics and superior therapeutics.

Keywords

SjšgrenÕs syndrome ¥ Lacrimal keratoconjunctivitis ¥ Ocular surface ¥ Lacrimal functional unit ¥ Autoimmunity ¥ Inßammation ¥ T cells