Severity of Sjögren’s Syndrome Keratoconjunctivitis Sicca Increases with Increased Percentage of Conjunctival Antigen-Presenting Cells

Abstract

This study investigated the relationship between clinical severity and percentage of conjunctival antigen-presenting cells (APCs) in Sjögren’s syndrome (SS)-associated keratoconjunctivitis sicca (KCS). KCS clinical severity was based on symptom severity, tear volume, tear break-up time, and ocular surface dye staining. Conjunctival goblet cell density (GCD) was measured in periodic acid Schiff (PAS)-stained membranes. Conjunctival cells obtained by impression cytology were used for flow cytometry to measure percentages of CD45+HLA-DR+ APCs and mature CD11c+CD86+ dendritic cells (DCs). Compared to normal conjunctiva, the percentages of HLA-DR+ and CD11c+CD86+ cells were higher in the conjunctiva of the KCS group (p < 0.05). The percentage of CD45+HLA-DR+ cells positively correlated with clinical severity (r = 0.71, p < 0.05) and negatively correlated with GCD (r = −0.61, p < 0.05). Clinical severity also negatively correlated with GCD (r = −0.54, p < 0.05). These findings indicate that a higher percentage of APCs and mature DCs in the conjunctiva is associated with more severe KCS in SS. These APCs may contribute to the generation of the pathogenic Th1 cells that cause goblet cell loss in KCS.

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

“…Among the several cells and inflammatory mediators that are important for the ocular surface diseases, we found the number of research papers following this decreasing order: dendritic cells (19) > IL6 (15) > IL17 (8) > CD4 + and CD8 + T cells together (7). The eight diseases that matched the inclusion criteria of the study mentioned in the method section are: contact lens wear [15][16][17][18][19][20], corneal graft rejection [21][22][23], dry eye [6,[24][25][26][27][28][29][30][31][32][33][34], glaucoma [35][36][37][38][39][40][41][42], Graft-vs-host (GvHD) [43,44], keratitis [45][46][47], scleritis [48][49][50], and Sjögren's syndrome [28,29,[32][33][34][51][52][53]. This is a combination of different ocular surface disorders, the range of w...…”

Gpr125 identifies myoepithelial progenitors at tips of lacrimal ducts and is essential for tear film

“…Adgra3 cre/cre and Adgra3 lz/lz mice show inflammatory infiltration of lacrimal glandsInflammatory infiltration of lacrimal glands plays a significant role in the pathological mechanism of Sjogren's syndrome and is a frequent feature of sporadic DED(2)(3)(4)29).To test if Adgra3 mutant mice modeled this we examined histological sections of lacrimal glands and found foci, composed of small round cells, in both Adgra3 cre/cre(Figure 3B, S1) and Adgra3 lz/lz mice. Lack of immunostaining for cytokeratin5 (CK5) indicated that myoepithelial cells were lost in these regions(Figures 3C,D).…”

Mechanisms of Disease in Sjögren Syndrome—New Developments and Directions

“…Pflugfelder and colleagues report an increased number of HLA-DR + antigen-presenting and CD11c + CD86 + dendritic cells in SS bulbar conjunctiva compared to control non-dry eyes [5]. The percentage of HLA-DR + cells positively correlated with clinical severity APCs.…”