{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:36:08Z","timestamp":1790742968318,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY011915"],"award-info":[{"award-number":["EY011915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY002520"],"award-info":[{"award-number":["EY002520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY020799"],"award-info":[{"award-number":["EY020799"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AI036211"],"award-info":[{"award-number":["P30AI036211"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10RR024574"],"award-info":[{"award-number":["S10RR024574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the relationship between clinical severity and percentage of conjunctival antigen-presenting cells (APCs) in Sj\u00f6gren\u2019s 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 &lt; 0.05). The percentage of CD45+HLA-DR+ cells positively correlated with clinical severity (r = 0.71, p &lt; 0.05) and negatively correlated with GCD (r = \u22120.61, p &lt; 0.05). Clinical severity also negatively correlated with GCD (r = \u22120.54, p &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms19092760","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T10:57:59Z","timestamp":1536922679000},"page":"2760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Severity of Sj\u00f6gren\u2019s Syndrome Keratoconjunctivitis Sicca Increases with Increased Percentage of Conjunctival Antigen-Presenting Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Stephen C.","family":"Pflugfelder","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koray","family":"Gumus","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, Erciyes University School of Medicine, 38039 Kayseri, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Farley","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-5494","authenticated-orcid":false,"given":"Cintia S.","family":"De Paiva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0161-6420(90)32478-8","article-title":"Conjunctival cytologic features of primary Sjogren\u2019s syndrome","volume":"97","author":"Pflugfelder","year":"1990","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0161-6420(97)30330-3","article-title":"Correlation of goblet cell density and mucosal epithelial membrane mucin expression with rose bengal staining in patients with ocular irritation","volume":"104","author":"Pflugfelder","year":"1997","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1167\/iovs.15-17627","article-title":"Aqueous tear deficiency increases conjunctival interferon-\u03b3 (IFN-\u03b3) expression and goblet cell loss","volume":"56","author":"Pflugfelder","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.ajpath.2016.02.004","article-title":"Interferon-\u03b3-induced unfolded protein response in conjunctival goblet cells as a cause of mucin deficiency in Sjogren syndrome","volume":"186","author":"Coursey","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1167\/iovs.07-0069","article-title":"Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-\u03b3","volume":"48","author":"Villarreal","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Barbosa, F.L., Xiao, Y., Bian, F., Coursey, T.G., Ko, B.Y., Clevers, H., de Paiva, C.S., and Pflugfelder, S.C. (2017). Goblet cells contribute to ocular surface immune tolerance-implications for dry eye disease. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050978"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Contreras-Ruiz, L., and Masli, S. (2015). Immunomodulatory cross-talk between conjunctival goblet cells and dendritic cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120284"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ko, B.Y., Xiao, Y., Barbosa, F.L., de Paiva, C.S., and Pflugfelder, S.C. (2018). Goblet cell loss abrogates ocular surface immune tolerance. JCI Insight, 3.","DOI":"10.1172\/jci.insight.98222"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xiao, Y., De Paiva, C.S., Yu, Z., Guimaraes de Souza, R., Li, D.Q., and Pflugfelder, S.C. (2018). Goblet cell produced retinoic acid suppresses CD86 expression and IL-12 production in bone marrow derived cells. Int. Immunol.","DOI":"10.1093\/intimm\/dxy045"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1126\/science.1237910","article-title":"Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals","volume":"342","author":"Shan","year":"2013","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.exer.2013.03.018","article-title":"HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease","volume":"111","author":"Epstein","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_12","first-page":"2199","article-title":"Interferon-\u03b3 induces apoptosis and expression of inflammation-related proteins in Chang conjunctival cells","volume":"40","author":"Brignole","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1097\/01.ico.0000157421.93522.00","article-title":"Distribution of conjunctival HLA-DR expression and the pathogenesis of damage in early dry eyes","volume":"24","author":"Rolando","year":"2005","journal-title":"Cornea"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/S0161-6420(00)00347-X","article-title":"Flow cytometric analysis of conjunctival epithelium in ocular rosacea and keratoconjunctivitis sicca","volume":"107","author":"Pisella","year":"2000","journal-title":"Ophthalmology"},{"key":"ref_15","first-page":"1356","article-title":"Flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes","volume":"41","author":"Brignole","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1167\/iovs.11-7215","article-title":"Hyperosmolar stress upregulates HLA-DR expression in human conjunctival epithelium in dry eye patients and in vitro models","volume":"52","author":"Versura","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/sj.eye.6702435","article-title":"Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis","volume":"21","author":"Mrugacz","year":"2007","journal-title":"Eye"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1097\/ICO.0b013e318299549c","article-title":"Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe keratoconjunctivitis sicca: A randomized double-blind clinical trial","volume":"32","author":"Sheppard","year":"2013","journal-title":"Cornea"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1542-0124(12)70085-X","article-title":"Management and therapy of dry eye disease: Report of the management and therapy subcommittee of the international dry eye workshop (2007)","volume":"5","author":"Pflugfelder","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.exer.2010.07.008","article-title":"Immune response in the conjunctival epithelium of patients with dry eye","volume":"91","author":"Barabino","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ajo.2009.09.013","article-title":"A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren\u2019s Syndrome International Registry","volume":"149","author":"Whitcher","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3109\/08830185.2012.748052","article-title":"Dry eye as a mucosal autoimmune disease","volume":"32","author":"Stern","year":"2013","journal-title":"Int. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.ophtha.2017.07.010","article-title":"The pathophysiology of dry eye disease: What we know and future directions for research","volume":"124","author":"Pflugfelder","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/mi.2012.27","article-title":"Topographical distribution and characterization of epithelial cells and intraepithelial lymphocytes in the human ocular mucosa","volume":"5","author":"Reinoso","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Said, A., and Weindl, G. (2015). Regulation of Dendritic Cell Function in Inflammation. J. Immunol. Res., 2015.","DOI":"10.1155\/2015\/743169"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/mi.2009.5","article-title":"IL-17 disrupts corneal barrier following desiccating stress","volume":"2","author":"Chotikavanich","year":"2009","journal-title":"Mucosal Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1167\/iovs.07-0002","article-title":"Expression of Th-1 chemokines and chemokine receptors on the ocular surface of C57BL\/6 mice: Effects of desiccating stress","volume":"48","author":"Yoon","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.4049\/jimmunol.1101442","article-title":"Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis","volume":"187","author":"Schaumburg","year":"2011","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/acr.21591","article-title":"Sjogren\u2019s International Collaborative Clinical Alliance Research, G. American College of Rheumatology classification criteria for Sjogren\u2019s syndrome: A data-driven, expert consensus approach in the Sjogren\u2019s International Collaborative Clinical Alliance cohort","volume":"64","author":"Shiboski","year":"2012","journal-title":"Arthrit. Care Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1167\/iovs.09-3875","article-title":"Association between high tear epidermal growth factor levels and corneal subepithelial fibrosis in dry eye conditions","volume":"51","author":"Rao","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ajo.2013.09.024","article-title":"Tear meniscus dimensions in tear dysfunction and their correlation with clinical parameters","volume":"157","author":"Tung","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/ICO.0b013e318158f6dc","article-title":"Effects of sequential artificial tear and cyclosporine emulsion therapy on conjunctival goblet cell density and transforming growth factor-\u03b22 production","volume":"27","author":"Pflugfelder","year":"2008","journal-title":"Cornea"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2760\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:20:27Z","timestamp":1760196027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,14]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["ijms19092760"],"URL":"https:\/\/doi.org\/10.3390\/ijms19092760","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,14]]}}}