Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration
Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of...
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| Veröffentlicht in: | Experimental eye research 2025-01, Vol.250, p.110154, Article 110154 |
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| creator | Rijken, Rianne Pameijer, Els M. Gerritsen, Bram Hiddingh, Sanne Stehouwer, Marilette de Boer, Joke H. Imhof, Saskia M. van Leeuwen, Redmer Kuiper, Jonas JW |
| description | Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients. A standardized 31-parameter flow cytometry analysis was conducted on peripheral blood mononuclear cells from 59 patients with early and advanced AMD and 39 controls without AMD, all older than 65 years. Fundus photography and optical coherence tomography were used to classify disease stages and a custom genotype array was used to compute an AMD genetic risk score based on 52 AMD disease risk variants (GRS-52). A generalized linear regression model corrected for age, sex, and smoking status revealed that AMD patients showed decreased frequencies of CD4+ T helper cell population expressing Integrin Alpha E (CD103) (Padj = 0.019). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4+ T helper cells (Padj = 0.013; |
| doi_str_mv | 10.1016/j.exer.2024.110154 |
| format | Article |
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•In peripheral blood, AMD patients exhibited decreased frequencies of CD4+ T helper cells expressing Integrin Alpha E (CD103).•Increased interleukin-4 (IL-4)-producing CD4+ T helper cells were observed in the peripheral blood of early AMD patients.•Reclassification by AMD genetic risk score (GRS-52) showed decreased IL-17-producing T cells in blood across GRS-52 categories.</description><identifier>ISSN: 0014-4835</identifier><identifier>ISSN: 1096-0007</identifier><identifier>EISSN: 1096-0007</identifier><identifier>DOI: 10.1016/j.exer.2024.110154</identifier><identifier>PMID: 39547643</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Age-related macular degeneration ; Aged ; Aged, 80 and over ; CD103 ; Cytokines - genetics ; Cytokines - metabolism ; Female ; Flow Cytometry ; Genetic Predisposition to Disease ; Genetic Risk Score ; GRS-52 ; Humans ; Interleukin-17 ; Interleukin-4 ; Macular Degeneration - blood ; Macular Degeneration - genetics ; Macular Degeneration - metabolism ; Male ; Peripheral blood ; Risk Factors ; T cells ; Tomography, Optical Coherence</subject><ispartof>Experimental eye research, 2025-01, Vol.250, p.110154, Article 110154</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-54bee7ad296a9c146b43a38b2dc5a00813612769ea1a31fed1cc0a54488846f13</cites><orcidid>0000-0002-0873-6368</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014483524003762$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39547643$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rijken, Rianne</creatorcontrib><creatorcontrib>Pameijer, Els M.</creatorcontrib><creatorcontrib>Gerritsen, Bram</creatorcontrib><creatorcontrib>Hiddingh, Sanne</creatorcontrib><creatorcontrib>Stehouwer, Marilette</creatorcontrib><creatorcontrib>de Boer, Joke H.</creatorcontrib><creatorcontrib>Imhof, Saskia M.</creatorcontrib><creatorcontrib>van Leeuwen, Redmer</creatorcontrib><creatorcontrib>Kuiper, Jonas JW</creatorcontrib><title>Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration</title><title>Experimental eye research</title><addtitle>Exp Eye Res</addtitle><description>Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients. A standardized 31-parameter flow cytometry analysis was conducted on peripheral blood mononuclear cells from 59 patients with early and advanced AMD and 39 controls without AMD, all older than 65 years. Fundus photography and optical coherence tomography were used to classify disease stages and a custom genotype array was used to compute an AMD genetic risk score based on 52 AMD disease risk variants (GRS-52). A generalized linear regression model corrected for age, sex, and smoking status revealed that AMD patients showed decreased frequencies of CD4+ T helper cell population expressing Integrin Alpha E (CD103) (Padj = 0.019). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4+ T helper cells (Padj = 0.013; <0.001), as well as IL-4-producing cytotoxic CD8+ T cells (Padj = 0.016; <0.001). Reclassification of samples based on the GRS-52 revealed that IL-17-producing T cells decreased incrementally across GRS-52 categories. In AMD, alterations in peripheral blood leukocyte populations are associated with genetic risk score and disease stage and include specifically IL-4 and IL-17A cytokine-producing and CD103 integrin-expressing T cell populations.
•In peripheral blood, AMD patients exhibited decreased frequencies of CD4+ T helper cells expressing Integrin Alpha E (CD103).•Increased interleukin-4 (IL-4)-producing CD4+ T helper cells were observed in the peripheral blood of early AMD patients.•Reclassification by AMD genetic risk score (GRS-52) showed decreased IL-17-producing T cells in blood across GRS-52 categories.</description><subject>Age-related macular degeneration</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>CD103</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Risk Score</subject><subject>GRS-52</subject><subject>Humans</subject><subject>Interleukin-17</subject><subject>Interleukin-4</subject><subject>Macular Degeneration - blood</subject><subject>Macular Degeneration - genetics</subject><subject>Macular Degeneration - metabolism</subject><subject>Male</subject><subject>Peripheral blood</subject><subject>Risk Factors</subject><subject>T cells</subject><subject>Tomography, Optical Coherence</subject><issn>0014-4835</issn><issn>1096-0007</issn><issn>1096-0007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFOGzEURa0KVFLgB7pAXrKZYI89nhmpmxZBWwmJDaytF_sldZjYYHtoWfPjeJKUJStLz-de6R5CvnI254yri_Uc_2Gc16yWc14ujfxEZpz1qmKMtQdkxhiXlexEc0S-pLQuVyFb-Zkcib6RrZJiRl5_DCFY6nzGVXS-ouAtNS85PDiP1WMMdjTOr-gdNTgMiUJECikF4yCjpX9d_kNThhVugyv0mJ2h0aUHmkwosPO0_FYRh21gA2YcIFKLExshu-BPyOEShoSn-_eY3F9f3V3-qm5uf_6-_H5TmVq0uWrkArEFW_cKesOlWkgBolvU1jTAWMeF4nWregQOgi_RcmMYNFJ2XSfVkotjcr7rLbOeRkxZb1yaZoHHMCYteN31HWukKmi9Q00MKUVc6sfoNhBfNGd6kq_XepKvJ_l6J7-Ezvb942KD9j3y33YBvu0ALCufXYkn49AbtC6iydoG91H_G8pilvs</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Rijken, Rianne</creator><creator>Pameijer, Els M.</creator><creator>Gerritsen, Bram</creator><creator>Hiddingh, Sanne</creator><creator>Stehouwer, Marilette</creator><creator>de Boer, Joke H.</creator><creator>Imhof, Saskia M.</creator><creator>van Leeuwen, Redmer</creator><creator>Kuiper, Jonas JW</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><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/0000-0002-0873-6368</orcidid></search><sort><creationdate>202501</creationdate><title>Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration</title><author>Rijken, Rianne ; Pameijer, Els M. ; Gerritsen, Bram ; Hiddingh, Sanne ; Stehouwer, Marilette ; de Boer, Joke H. ; Imhof, Saskia M. ; van Leeuwen, Redmer ; Kuiper, Jonas JW</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c237t-54bee7ad296a9c146b43a38b2dc5a00813612769ea1a31fed1cc0a54488846f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Age-related macular degeneration</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>CD103</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Risk Score</topic><topic>GRS-52</topic><topic>Humans</topic><topic>Interleukin-17</topic><topic>Interleukin-4</topic><topic>Macular Degeneration - blood</topic><topic>Macular Degeneration - genetics</topic><topic>Macular Degeneration - metabolism</topic><topic>Male</topic><topic>Peripheral blood</topic><topic>Risk Factors</topic><topic>T cells</topic><topic>Tomography, Optical Coherence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rijken, Rianne</creatorcontrib><creatorcontrib>Pameijer, Els M.</creatorcontrib><creatorcontrib>Gerritsen, Bram</creatorcontrib><creatorcontrib>Hiddingh, Sanne</creatorcontrib><creatorcontrib>Stehouwer, Marilette</creatorcontrib><creatorcontrib>de Boer, Joke H.</creatorcontrib><creatorcontrib>Imhof, Saskia M.</creatorcontrib><creatorcontrib>van Leeuwen, Redmer</creatorcontrib><creatorcontrib>Kuiper, Jonas JW</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Experimental eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rijken, Rianne</au><au>Pameijer, Els M.</au><au>Gerritsen, Bram</au><au>Hiddingh, Sanne</au><au>Stehouwer, Marilette</au><au>de Boer, Joke H.</au><au>Imhof, Saskia M.</au><au>van Leeuwen, Redmer</au><au>Kuiper, Jonas JW</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration</atitle><jtitle>Experimental eye research</jtitle><addtitle>Exp Eye Res</addtitle><date>2025-01</date><risdate>2025</risdate><volume>250</volume><spage>110154</spage><pages>110154-</pages><artnum>110154</artnum><issn>0014-4835</issn><issn>1096-0007</issn><eissn>1096-0007</eissn><abstract>Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients. A standardized 31-parameter flow cytometry analysis was conducted on peripheral blood mononuclear cells from 59 patients with early and advanced AMD and 39 controls without AMD, all older than 65 years. Fundus photography and optical coherence tomography were used to classify disease stages and a custom genotype array was used to compute an AMD genetic risk score based on 52 AMD disease risk variants (GRS-52). A generalized linear regression model corrected for age, sex, and smoking status revealed that AMD patients showed decreased frequencies of CD4+ T helper cell population expressing Integrin Alpha E (CD103) (Padj = 0.019). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4+ T helper cells (Padj = 0.013; <0.001), as well as IL-4-producing cytotoxic CD8+ T cells (Padj = 0.016; <0.001). Reclassification of samples based on the GRS-52 revealed that IL-17-producing T cells decreased incrementally across GRS-52 categories. In AMD, alterations in peripheral blood leukocyte populations are associated with genetic risk score and disease stage and include specifically IL-4 and IL-17A cytokine-producing and CD103 integrin-expressing T cell populations.
•In peripheral blood, AMD patients exhibited decreased frequencies of CD4+ T helper cells expressing Integrin Alpha E (CD103).•Increased interleukin-4 (IL-4)-producing CD4+ T helper cells were observed in the peripheral blood of early AMD patients.•Reclassification by AMD genetic risk score (GRS-52) showed decreased IL-17-producing T cells in blood across GRS-52 categories.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>39547643</pmid><doi>10.1016/j.exer.2024.110154</doi><orcidid>https://orcid.org/0000-0002-0873-6368</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age-related macular degeneration Aged Aged, 80 and over CD103 Cytokines - genetics Cytokines - metabolism Female Flow Cytometry Genetic Predisposition to Disease Genetic Risk Score GRS-52 Humans Interleukin-17 Interleukin-4 Macular Degeneration - blood Macular Degeneration - genetics Macular Degeneration - metabolism Male Peripheral blood Risk Factors T cells Tomography, Optical Coherence |
| title | Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration |
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