Elevated neutrophils and reduced NK cells are associated with altered tear molecular signatures and clinical sequelae of chronic ocular Stevens-Johnson syndrome
Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients. 2...
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| Veröffentlicht in: | The ocular surface 2024-10, Vol.34, p.9-21 |
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| creator | D'Souza, Sharon Nair, Archana Padmanabhan Ashok, Nikhil Kannan, Ramaraj Dickman, Mor M. Nuijts, Rudy M.M.A. Shetty, Rohit Sethu, Swaminathan Ghosh, Arkasubhra |
| description | Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients.
21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples.
Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p |
| doi_str_mv | 10.1016/j.jtos.2024.04.003 |
| format | Article |
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21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples.
Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/β/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy.
Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.</description><identifier>ISSN: 1542-0124</identifier><identifier>ISSN: 1937-5913</identifier><identifier>EISSN: 1937-5913</identifier><identifier>DOI: 10.1016/j.jtos.2024.04.003</identifier><identifier>PMID: 38703818</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Chronic Disease ; Cornea ; Cytokines ; Cytokines - metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Immune cells ; Inflammation ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Male ; Middle Aged ; Natural killer cells ; Neutrophils ; Neutrophils - immunology ; Neutrophils - metabolism ; SJS ; Stevens-Johnson Syndrome - complications ; Stevens-Johnson Syndrome - immunology ; Stevens-Johnson Syndrome - metabolism ; Tears - metabolism ; Young Adult</subject><ispartof>The ocular surface, 2024-10, Vol.34, p.9-21</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-fd0cb82c0ec7f2f0712efe2e6a355b6128e8116082de07c29275090dc9d0dd3</cites><orcidid>0000-0002-6570-5891</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38703818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>D'Souza, Sharon</creatorcontrib><creatorcontrib>Nair, Archana Padmanabhan</creatorcontrib><creatorcontrib>Ashok, Nikhil</creatorcontrib><creatorcontrib>Kannan, Ramaraj</creatorcontrib><creatorcontrib>Dickman, Mor M.</creatorcontrib><creatorcontrib>Nuijts, Rudy M.M.A.</creatorcontrib><creatorcontrib>Shetty, Rohit</creatorcontrib><creatorcontrib>Sethu, Swaminathan</creatorcontrib><creatorcontrib>Ghosh, Arkasubhra</creatorcontrib><title>Elevated neutrophils and reduced NK cells are associated with altered tear molecular signatures and clinical sequelae of chronic ocular Stevens-Johnson syndrome</title><title>The ocular surface</title><addtitle>Ocul Surf</addtitle><description>Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients.
21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples.
Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/β/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy.
Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.</description><subject>Adult</subject><subject>Chronic Disease</subject><subject>Cornea</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immune cells</subject><subject>Inflammation</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Natural killer cells</subject><subject>Neutrophils</subject><subject>Neutrophils - immunology</subject><subject>Neutrophils - metabolism</subject><subject>SJS</subject><subject>Stevens-Johnson Syndrome - complications</subject><subject>Stevens-Johnson Syndrome - immunology</subject><subject>Stevens-Johnson Syndrome - metabolism</subject><subject>Tears - metabolism</subject><subject>Young Adult</subject><issn>1542-0124</issn><issn>1937-5913</issn><issn>1937-5913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1uFDEQhEcIRELgBTggH7nM0rZ3_iQuKAqQEMEh3C2v3cN65bEXt2ejvA2PiocJHJFacqv0VcmtqqrXHDYcePvusDnkSBsBYruBMiCfVOd8kF3dDFw-LXuzFTVwsT2rXhAdCtC2IJ5XZ7LvQPa8P69-XXk86YyWBZxzise988R0sCyhnU3Rv35hBv0iJmSaKBr3h793ec-0z1hAllEnNkWPZvZlI_cj6DwnXKOMd8EZ7Rnhzxm9RhZHZvYpFpXF1XKX8YSB6pu4DxQDo4dgU5zwZfVs1J7w1eN7Ud19vPp--bm-_fbp-vLDbW2E7HI9WjC7XhhA041ihI4LHFFgq2XT7Foueuw5b6EXFqEzYhBdAwNYM1iwVl5Ub9fUY4rli5TV5Gg5WweMMykJhd7yDkRBxYqaFIkSjuqY3KTTg-Kgll7UQS29qKUXBWVAFtObx_x5N6H9Z_lbRAHerwCWG08OkyLjMJQCXEKTlY3uf_m_AcOrovA</recordid><startdate>202410</startdate><enddate>202410</enddate><creator>D'Souza, Sharon</creator><creator>Nair, Archana Padmanabhan</creator><creator>Ashok, Nikhil</creator><creator>Kannan, Ramaraj</creator><creator>Dickman, Mor M.</creator><creator>Nuijts, Rudy M.M.A.</creator><creator>Shetty, Rohit</creator><creator>Sethu, Swaminathan</creator><creator>Ghosh, Arkasubhra</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6570-5891</orcidid></search><sort><creationdate>202410</creationdate><title>Elevated neutrophils and reduced NK cells are associated with altered tear molecular signatures and clinical sequelae of chronic ocular Stevens-Johnson syndrome</title><author>D'Souza, Sharon ; Nair, Archana Padmanabhan ; Ashok, Nikhil ; Kannan, Ramaraj ; Dickman, Mor M. ; Nuijts, Rudy M.M.A. ; Shetty, Rohit ; Sethu, Swaminathan ; Ghosh, Arkasubhra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c237t-fd0cb82c0ec7f2f0712efe2e6a355b6128e8116082de07c29275090dc9d0dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Chronic Disease</topic><topic>Cornea</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immune cells</topic><topic>Inflammation</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Natural killer cells</topic><topic>Neutrophils</topic><topic>Neutrophils - immunology</topic><topic>Neutrophils - metabolism</topic><topic>SJS</topic><topic>Stevens-Johnson Syndrome - complications</topic><topic>Stevens-Johnson Syndrome - immunology</topic><topic>Stevens-Johnson Syndrome - metabolism</topic><topic>Tears - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>D'Souza, Sharon</creatorcontrib><creatorcontrib>Nair, Archana Padmanabhan</creatorcontrib><creatorcontrib>Ashok, Nikhil</creatorcontrib><creatorcontrib>Kannan, Ramaraj</creatorcontrib><creatorcontrib>Dickman, Mor M.</creatorcontrib><creatorcontrib>Nuijts, Rudy M.M.A.</creatorcontrib><creatorcontrib>Shetty, Rohit</creatorcontrib><creatorcontrib>Sethu, Swaminathan</creatorcontrib><creatorcontrib>Ghosh, Arkasubhra</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The ocular surface</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>D'Souza, Sharon</au><au>Nair, Archana Padmanabhan</au><au>Ashok, Nikhil</au><au>Kannan, Ramaraj</au><au>Dickman, Mor M.</au><au>Nuijts, Rudy M.M.A.</au><au>Shetty, Rohit</au><au>Sethu, Swaminathan</au><au>Ghosh, Arkasubhra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated neutrophils and reduced NK cells are associated with altered tear molecular signatures and clinical sequelae of chronic ocular Stevens-Johnson syndrome</atitle><jtitle>The ocular surface</jtitle><addtitle>Ocul Surf</addtitle><date>2024-10</date><risdate>2024</risdate><volume>34</volume><spage>9</spage><epage>21</epage><pages>9-21</pages><issn>1542-0124</issn><issn>1937-5913</issn><eissn>1937-5913</eissn><abstract>Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients.
21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples.
Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/β/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy.
Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38703818</pmid><doi>10.1016/j.jtos.2024.04.003</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6570-5891</orcidid></addata></record> |
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| ispartof | The ocular surface, 2024-10, Vol.34, p.9-21 |
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| subjects | Adult Chronic Disease Cornea Cytokines Cytokines - metabolism Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Humans Immune cells Inflammation Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Male Middle Aged Natural killer cells Neutrophils Neutrophils - immunology Neutrophils - metabolism SJS Stevens-Johnson Syndrome - complications Stevens-Johnson Syndrome - immunology Stevens-Johnson Syndrome - metabolism Tears - metabolism Young Adult |
| title | Elevated neutrophils and reduced NK cells are associated with altered tear molecular signatures and clinical sequelae of chronic ocular Stevens-Johnson syndrome |
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