SJOGRENS-SYNDROME - CYTOKINE AND EPSTEIN-BARR VIRAL GENE-EXPRESSION WITHIN THE CONJUNCTIVAL EPITHELIUM

Purpose. In primary Sjogren's syndrome (SS), ocular surface changes wi thin the conjunctival epithelium include lymphocytic infiltration, squ amous cell metaplasia, and a reduction in goblet cell number. These ch anges may be the simple result of increased mechanical abrasion second ary to dryness. Alternatively, they may represent a local response to ocular and/or systemic inflammatory processes, perhaps in response to Epstein-Barr viral (EBV) infection, an agent recently implicated in th e etiology of SS. To determine whether inflammatory processes or local infection by EBV contribute to the ocular surface pathology of SS, we examined the expression of inflammatory cell surface markers, cytokin es, and EBV gene products within the ocular conjunctiva of patients wi th SS. Methods. Ocular conjunctival tissue was isolated from patients with primary SS and nondry eye control patients by impression cytology or direct biopsy. These specimens were examined by immunofluorescence microscopy and reverse-transcriptase polymerase chain reaction (RT-PC R) for the expression of various markers. Results. The authors found t he frequency of expression of HLA-DR (P < 0.0001), ICAM-1 (P < 0.035), and IL-6 (P < 0.0001) to be significantly elevated in patients with p rimary SS versus nondry eye control patients. The IL-2 receptor and cy tokines IL-1 beta and IL-8 were each found to be expressed with relati vely high frequency in both patient populations, whereas mRNAs encodin g cytokines IL-2, IFN-gamma, GM-CSF, and TGF-beta were not reproducibl y detectable in either population. Messenger RNA encoding a marker for passive-latent EBV infection (EBNA-1) was detected with high frequenc y in both SS and normal populations. The EBV IL-10 analog BCRF-1 was e xpressed with low frequency in the SS population; however, these level s were not significantly different from the control population. The ex pression of two other markers of EBV infection, latent membrane protei n (LMP, a lytic and latent marker), and BZLF-1 (putative latent-lytic switch gene) was undetectable in either study population. Conclusion. Based on the increased expression of the cell surface molecules HLA-DR and ICAM-1, and the inflammatory cytokine IL-6, the authors propose t hat local inflammatory processes contribute to the ocular surface chan ges and ocular surface dryness associated with primary SS.