Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis
Ocular complications related to Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative c...
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Veröffentlicht in: | Investigative ophthalmology & visual science 2013-07, Vol.54 (7), p.4578 |
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creator | Williams, Geraint P Tomlins, Paul J Denniston, Alastair K Southworth, H Susan Sreekantham, Sreekanth Curnow, S John Rauz, Saaeha |
description | Ocular complications related to Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative conjunctival cellular profiles during acute (12 months) disease.
Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21).
Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(-) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = -0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0).
These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression. |
doi_str_mv | 10.1167/iovs.13-11859 |
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Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21).
Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(-) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = -0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0).
These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression.</description><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.13-11859</identifier><identifier>PMID: 23737478</identifier><language>eng</language><publisher>United States</publisher><subject>Acute Disease ; Adolescent ; Adult ; Antigens, CD - immunology ; Chronic Disease ; Conjunctiva - pathology ; Conjunctival Diseases - immunology ; Cross-Sectional Studies ; Epithelium - immunology ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Neutrophils - immunology ; Stevens-Johnson Syndrome - immunology ; Young Adult</subject><ispartof>Investigative ophthalmology & visual science, 2013-07, Vol.54 (7), p.4578</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23737478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Williams, Geraint P</creatorcontrib><creatorcontrib>Tomlins, Paul J</creatorcontrib><creatorcontrib>Denniston, Alastair K</creatorcontrib><creatorcontrib>Southworth, H Susan</creatorcontrib><creatorcontrib>Sreekantham, Sreekanth</creatorcontrib><creatorcontrib>Curnow, S John</creatorcontrib><creatorcontrib>Rauz, Saaeha</creatorcontrib><title>Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>Ocular complications related to Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative conjunctival cellular profiles during acute (<12 months) and chronic (>12 months) disease.
Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21).
Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(-) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = -0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0).
These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression.</description><subject>Acute Disease</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Antigens, CD - immunology</subject><subject>Chronic Disease</subject><subject>Conjunctiva - pathology</subject><subject>Conjunctival Diseases - immunology</subject><subject>Cross-Sectional Studies</subject><subject>Epithelium - immunology</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neutrophils - immunology</subject><subject>Stevens-Johnson Syndrome - immunology</subject><subject>Young Adult</subject><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kDFOwzAYRi0kREthZEW-QIp_O4mdEaUFihAMdK-c2FFdOXYUJxEdewPOA7fpSQgqTO-b3pM-hG6AzAFSfmf8EObAIgCRZGdoCklCo4QLNkGXIewIoQCUXKAJZZzxmIsp-lxaPcjOeId9hUvvdr0rOzNIi3Vjuq22Zpz5Ik5Wr-t8AVAcD18j0xPi4-EbO913rW-2xgZsRk_ZW9ni904P2oXo2W9dGPVh71Tra42lU7jzH6b8LSjd1mPA6bL1dh9MuELnlbRBX_9xhtYPy3X-FL28Pa7y-5doBylkEVeEqAxKImkmNaMVpDqVknDKKkoKLYTghUrLgsRCFRUIImG8hWaqEgmv2AzdnrRNX9RabZrW1LLdb_6fYT9csmid</recordid><startdate>20130710</startdate><enddate>20130710</enddate><creator>Williams, Geraint P</creator><creator>Tomlins, Paul J</creator><creator>Denniston, Alastair K</creator><creator>Southworth, H Susan</creator><creator>Sreekantham, Sreekanth</creator><creator>Curnow, S John</creator><creator>Rauz, Saaeha</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20130710</creationdate><title>Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis</title><author>Williams, Geraint P ; Tomlins, Paul J ; Denniston, Alastair K ; Southworth, H Susan ; Sreekantham, Sreekanth ; Curnow, S John ; Rauz, Saaeha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j1619-7d00d91c0a29ae32f16e6aa0723f20be8887bd6cb048dbf180a111829df857f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute Disease</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Antigens, CD - immunology</topic><topic>Chronic Disease</topic><topic>Conjunctiva - pathology</topic><topic>Conjunctival Diseases - immunology</topic><topic>Cross-Sectional Studies</topic><topic>Epithelium - immunology</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neutrophils - immunology</topic><topic>Stevens-Johnson Syndrome - immunology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Williams, Geraint P</creatorcontrib><creatorcontrib>Tomlins, Paul J</creatorcontrib><creatorcontrib>Denniston, Alastair K</creatorcontrib><creatorcontrib>Southworth, H Susan</creatorcontrib><creatorcontrib>Sreekantham, Sreekanth</creatorcontrib><creatorcontrib>Curnow, S John</creatorcontrib><creatorcontrib>Rauz, Saaeha</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Williams, Geraint P</au><au>Tomlins, Paul J</au><au>Denniston, Alastair K</au><au>Southworth, H Susan</au><au>Sreekantham, Sreekanth</au><au>Curnow, S John</au><au>Rauz, Saaeha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2013-07-10</date><risdate>2013</risdate><volume>54</volume><issue>7</issue><spage>4578</spage><pages>4578-</pages><eissn>1552-5783</eissn><abstract>Ocular complications related to Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative conjunctival cellular profiles during acute (<12 months) and chronic (>12 months) disease.
Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21).
Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(-) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = -0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0).
These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression.</abstract><cop>United States</cop><pmid>23737478</pmid><doi>10.1167/iovs.13-11859</doi><oa>free_for_read</oa></addata></record> |
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subjects | Acute Disease Adolescent Adult Antigens, CD - immunology Chronic Disease Conjunctiva - pathology Conjunctival Diseases - immunology Cross-Sectional Studies Epithelium - immunology Female Flow Cytometry Humans Male Middle Aged Neutrophils - immunology Stevens-Johnson Syndrome - immunology Young Adult |
title | Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis |
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