{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:48:44Z","timestamp":1785887324364,"version":"3.56.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005809","name":"Hyderabad Eye Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis (SJS\/TEN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS\/TEN patients (<jats:italic>n<\/jats:italic>\u2009=\u200922 eyes) and age\u2010 and gender\u2010matched controls (<jats:italic>n<\/jats:italic>\u2009=\u200922 eyes). The candidate proteins were validated using ELISA (<jats:italic>n<\/jats:italic>\u2009=\u200980 eyes) in tear samples and immunohistochemistry (IHC; <jats:italic>n<\/jats:italic> = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS\/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001), defensin (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001), and matrix metalloproteinase 8 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). The presence of neutrophils was confirmed by the upregulation of IL\u20108 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS\/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL\u201036\u03b3 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01) was expressed in three SJS\/TEN patients and was confirmed in SJS\/TEN tears and eyelid margins by ELISA and IHC, respectively. IL\u201036\u03b3 was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) and opiorphin (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.002). Neutrophil elastase (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.02) was significantly elevated in patients with severe eyelid margin keratinization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL\u201036\u03b3, potentially mediated by neutrophils recruited via IL\u20108. Future experimental studies are needed to test the role of therapies targeting IL\u20108 and\/or IL\u201036\u03b3 in reducing eyelid margin keratinization and its associated ocular complications in SJS\/TEN.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16126","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T08:10:52Z","timestamp":1714378252000},"page":"2128-2143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neutrophil\u2010driven and interleukin\u201036\u03b3\u2010associated ocular surface inflammation in chronic Stevens\u2013Johnson syndrome"],"prefix":"10.1111","volume":"79","author":[{"given":"Madhuri Amulya","family":"Koduri","sequence":"first","affiliation":[{"name":"Centre for Ocular Regeneration (CORE) Prof. Brien Holden Eye Research Centre (BHERC) L V Prasad Eye Institute  Hyderabad Telangana India"},{"name":"Manipal Academy of Higher Education (MAHE)  Manipal 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