{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:05:10Z","timestamp":1790910310471,"version":"4.1.0"},"reference-count":170,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Sj\u00f6gren\u2019s syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with different types of severity, e.g., dry eye and dry mouth symptoms, due to early involvement of the lacrimal and salivary glands, which may be associated with parotid enlargement and dry eye; keratoconjunctivitis sicca (KCS) is its most common ocular manifestation. It is still doubtful if the extent ocular surface manifestations are secondary to lacrimal or meibomian gland involvement or to the targeting of corneal and conjunctival autoantigens. SS is the most representative cause of aqueous deficient dry eye, and the primary role of the inflammatory process was evidenced. Recent scientific progress in understanding the numerous factors involved in the pathogenesis of pSS was registered, but the exact mechanisms involved still need to be clarified. The unquestionable role of both the innate and adaptive immune system, participating actively in the induction and evolution of the disease, was recognized. The ocular surface inflammation is a central mechanism in pSS leading to the decrease of lacrimal secretion and keratoconjunctival alterations. However, there are controversies about whether the ocular surface involvement is a direct autoimmune target or secondary to the inflammatory process in the lacrimal gland. In this review, we aimed to present actual knowledge relative to the pathogenesis of the pSS, considering the role of innate immunity, adaptive immunity, and genetics.<\/jats:p>","DOI":"10.3390\/genes12030365","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Ophthalmologic Manifestations of Primary Sj\u00f6gren\u2019s Syndrome"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8083-3437","authenticated-orcid":false,"given":"Anna Maria","family":"Roszkowska","sequence":"first","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-9756","authenticated-orcid":false,"given":"Giovanni William","family":"Oliverio","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Aragona","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Ophthalmology Clinic, Vita Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Inferrera","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Antonella","family":"Severo","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Alessandrello","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Spinella","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Imelde","family":"Postorino","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-9799","authenticated-orcid":false,"given":"Pasquale","family":"Aragona","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mathews, P.M., Robinson, S.A., Gire, A., Baer, A.N., and Akpek, E.K. 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