Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk
Abstract Objectives Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and...
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| Veröffentlicht in: | Rheumatology (Oxford, England) England), 2021-02, Vol.60 (2), p.785-801 |
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| creator | Wienke, Judith Mertens, Jorre S Garcia, Samuel Lim, Johan Wijngaarde, Camiel A Yeo, Joo Guan Meyer, Alain van den Hoogen, Lucas L Tekstra, Janneke Hoogendijk, Jessica E Otten, Henny G Fritsch-Stork, Ruth D E de Jager, Wilco Seyger, Marieke M B Thurlings, Rogier M de Jong, Elke M G J van der Kooi, Anneke J van der Pol, W Ludo Arkachaisri, Thaschawee Radstake, Timothy R D J van Royen-Kerkhof, Annet van Wijk, Femke |
| description | Abstract
Objectives
Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD.
Methods
A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA.
Results
The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with ‘signature’ markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction.
Conclusion
CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term. |
| doi_str_mv | 10.1093/rheumatology/keaa270 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2435529303</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/rheumatology/keaa270</oup_id><sourcerecordid>2435529303</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4103-8523e1997efcbb0cb931d56a7c4e28973463f2a506831662cf99a01772f688f13</originalsourceid><addsrcrecordid>eNqNUctOG0EQHEVBMZj8QYTmmIvjeeyTW4IgIFnikpxX7dmeeOLZHTO9Y8lfwG-z2MbiyKm7papqVRVj36T4IUWt53GFqYMh-PBvN18jgCrFJ3Yus0LNhNbq82lX2YRdEP0XQuRSV1_YRKtKClWU5-z5lwsdxDVGvonBOo_Eg-XYt2FYoXfgOZjBbWFwoefQt7zdkU292d-u5xEictrRgJ0zHNIQXNelHnnrCIGQrrnrNt6ZvQJxGyI3EFsXtkAmeYg8OlpfsjMLnvDrcU7Z37vbPzf3s8Xj74ebn4uZyaTQsypXGmVdl2jNcinMstayzQsoTYaqqkudFdoqyEVRaVkUyti6BiHLUtmiqqzUU_b9oDu6fUpIQ9M5Mug99BgSNSrTea5qPSY4ZdkBamIgimibTXRjVrtGiua1guZ9Bc2xgpF2dfyQlh22J9Jb5iNgfgCEtPmY5Avnj5tH</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2435529303</pqid></control><display><type>article</type><title>Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Wienke, Judith ; Mertens, Jorre S ; Garcia, Samuel ; Lim, Johan ; Wijngaarde, Camiel A ; Yeo, Joo Guan ; Meyer, Alain ; van den Hoogen, Lucas L ; Tekstra, Janneke ; Hoogendijk, Jessica E ; Otten, Henny G ; Fritsch-Stork, Ruth D E ; de Jager, Wilco ; Seyger, Marieke M B ; Thurlings, Rogier M ; de Jong, Elke M G J ; van der Kooi, Anneke J ; van der Pol, W Ludo ; Arkachaisri, Thaschawee ; Radstake, Timothy R D J ; van Royen-Kerkhof, Annet ; van Wijk, Femke</creator><creatorcontrib>Wienke, Judith ; Mertens, Jorre S ; Garcia, Samuel ; Lim, Johan ; Wijngaarde, Camiel A ; Yeo, Joo Guan ; Meyer, Alain ; van den Hoogen, Lucas L ; Tekstra, Janneke ; Hoogendijk, Jessica E ; Otten, Henny G ; Fritsch-Stork, Ruth D E ; de Jager, Wilco ; Seyger, Marieke M B ; Thurlings, Rogier M ; de Jong, Elke M G J ; van der Kooi, Anneke J ; van der Pol, W Ludo ; Arkachaisri, Thaschawee ; Radstake, Timothy R D J ; van Royen-Kerkhof, Annet ; van Wijk, Femke ; Dutch Juvenile Myositis Consortium</creatorcontrib><description>Abstract
Objectives
Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD.
Methods
A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA.
Results
The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with ‘signature’ markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction.
Conclusion
CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term.</description><identifier>ISSN: 1462-0324</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/keaa270</identifier><identifier>PMID: 32810267</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Autoimmunity ; Biomarkers - blood ; Chemokine CXCL10 - blood ; Chemokine CXCL13 - blood ; Dermatomyositis - blood ; Dermatomyositis - diagnosis ; Endothelium, Vascular - immunology ; Eosinophilia - blood ; Eosinophilia - diagnosis ; Fasciitis - blood ; Fasciitis - diagnosis ; Female ; Galectins - blood ; Heart Disease Risk Factors ; Humans ; Male ; Middle Aged ; Monitoring, Immunologic - methods ; Netherlands ; Patient Acuity ; Receptors, Tumor Necrosis Factor, Type II - blood ; Scleroderma, Localized - blood ; Scleroderma, Localized - diagnosis ; Vascular Cell Adhesion Molecule-1 - blood</subject><ispartof>Rheumatology (Oxford, England), 2021-02, Vol.60 (2), p.785-801</ispartof><rights>Published by Oxford University Press on behalf of the British Society for Rheumatology 2020. 2020</rights><rights>Published by Oxford University Press on behalf of the British Society for Rheumatology 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4103-8523e1997efcbb0cb931d56a7c4e28973463f2a506831662cf99a01772f688f13</citedby><cites>FETCH-LOGICAL-c4103-8523e1997efcbb0cb931d56a7c4e28973463f2a506831662cf99a01772f688f13</cites><orcidid>0000-0002-3835-6374 ; 0000-0002-7565-1954 ; 0000-0002-1387-1169</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32810267$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wienke, Judith</creatorcontrib><creatorcontrib>Mertens, Jorre S</creatorcontrib><creatorcontrib>Garcia, Samuel</creatorcontrib><creatorcontrib>Lim, Johan</creatorcontrib><creatorcontrib>Wijngaarde, Camiel A</creatorcontrib><creatorcontrib>Yeo, Joo Guan</creatorcontrib><creatorcontrib>Meyer, Alain</creatorcontrib><creatorcontrib>van den Hoogen, Lucas L</creatorcontrib><creatorcontrib>Tekstra, Janneke</creatorcontrib><creatorcontrib>Hoogendijk, Jessica E</creatorcontrib><creatorcontrib>Otten, Henny G</creatorcontrib><creatorcontrib>Fritsch-Stork, Ruth D E</creatorcontrib><creatorcontrib>de Jager, Wilco</creatorcontrib><creatorcontrib>Seyger, Marieke M B</creatorcontrib><creatorcontrib>Thurlings, Rogier M</creatorcontrib><creatorcontrib>de Jong, Elke M G J</creatorcontrib><creatorcontrib>van der Kooi, Anneke J</creatorcontrib><creatorcontrib>van der Pol, W Ludo</creatorcontrib><creatorcontrib>Arkachaisri, Thaschawee</creatorcontrib><creatorcontrib>Radstake, Timothy R D J</creatorcontrib><creatorcontrib>van Royen-Kerkhof, Annet</creatorcontrib><creatorcontrib>van Wijk, Femke</creatorcontrib><creatorcontrib>Dutch Juvenile Myositis Consortium</creatorcontrib><title>Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk</title><title>Rheumatology (Oxford, England)</title><addtitle>Rheumatology (Oxford)</addtitle><description>Abstract
Objectives
Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD.
Methods
A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA.
Results
The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with ‘signature’ markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction.
Conclusion
CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term.</description><subject>Autoimmunity</subject><subject>Biomarkers - blood</subject><subject>Chemokine CXCL10 - blood</subject><subject>Chemokine CXCL13 - blood</subject><subject>Dermatomyositis - blood</subject><subject>Dermatomyositis - diagnosis</subject><subject>Endothelium, Vascular - immunology</subject><subject>Eosinophilia - blood</subject><subject>Eosinophilia - diagnosis</subject><subject>Fasciitis - blood</subject><subject>Fasciitis - diagnosis</subject><subject>Female</subject><subject>Galectins - blood</subject><subject>Heart Disease Risk Factors</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monitoring, Immunologic - methods</subject><subject>Netherlands</subject><subject>Patient Acuity</subject><subject>Receptors, Tumor Necrosis Factor, Type II - blood</subject><subject>Scleroderma, Localized - blood</subject><subject>Scleroderma, Localized - diagnosis</subject><subject>Vascular Cell Adhesion Molecule-1 - blood</subject><issn>1462-0324</issn><issn>1462-0332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUctOG0EQHEVBMZj8QYTmmIvjeeyTW4IgIFnikpxX7dmeeOLZHTO9Y8lfwG-z2MbiyKm7papqVRVj36T4IUWt53GFqYMh-PBvN18jgCrFJ3Yus0LNhNbq82lX2YRdEP0XQuRSV1_YRKtKClWU5-z5lwsdxDVGvonBOo_Eg-XYt2FYoXfgOZjBbWFwoefQt7zdkU292d-u5xEictrRgJ0zHNIQXNelHnnrCIGQrrnrNt6ZvQJxGyI3EFsXtkAmeYg8OlpfsjMLnvDrcU7Z37vbPzf3s8Xj74ebn4uZyaTQsypXGmVdl2jNcinMstayzQsoTYaqqkudFdoqyEVRaVkUyti6BiHLUtmiqqzUU_b9oDu6fUpIQ9M5Mug99BgSNSrTea5qPSY4ZdkBamIgimibTXRjVrtGiua1guZ9Bc2xgpF2dfyQlh22J9Jb5iNgfgCEtPmY5Avnj5tH</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Wienke, Judith</creator><creator>Mertens, Jorre S</creator><creator>Garcia, Samuel</creator><creator>Lim, Johan</creator><creator>Wijngaarde, Camiel A</creator><creator>Yeo, Joo Guan</creator><creator>Meyer, Alain</creator><creator>van den Hoogen, Lucas L</creator><creator>Tekstra, Janneke</creator><creator>Hoogendijk, Jessica E</creator><creator>Otten, Henny G</creator><creator>Fritsch-Stork, Ruth D E</creator><creator>de Jager, Wilco</creator><creator>Seyger, Marieke M B</creator><creator>Thurlings, Rogier M</creator><creator>de Jong, Elke M G J</creator><creator>van der Kooi, Anneke J</creator><creator>van der Pol, W Ludo</creator><creator>Arkachaisri, Thaschawee</creator><creator>Radstake, Timothy R D J</creator><creator>van Royen-Kerkhof, Annet</creator><creator>van Wijk, Femke</creator><general>Oxford University Press</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/0000-0002-3835-6374</orcidid><orcidid>https://orcid.org/0000-0002-7565-1954</orcidid><orcidid>https://orcid.org/0000-0002-1387-1169</orcidid></search><sort><creationdate>20210201</creationdate><title>Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk</title><author>Wienke, Judith ; Mertens, Jorre S ; Garcia, Samuel ; Lim, Johan ; Wijngaarde, Camiel A ; Yeo, Joo Guan ; Meyer, Alain ; van den Hoogen, Lucas L ; Tekstra, Janneke ; Hoogendijk, Jessica E ; Otten, Henny G ; Fritsch-Stork, Ruth D E ; de Jager, Wilco ; Seyger, Marieke M B ; Thurlings, Rogier M ; de Jong, Elke M G J ; van der Kooi, Anneke J ; van der Pol, W Ludo ; Arkachaisri, Thaschawee ; Radstake, Timothy R D J ; van Royen-Kerkhof, Annet ; van Wijk, Femke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4103-8523e1997efcbb0cb931d56a7c4e28973463f2a506831662cf99a01772f688f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Autoimmunity</topic><topic>Biomarkers - blood</topic><topic>Chemokine CXCL10 - blood</topic><topic>Chemokine CXCL13 - blood</topic><topic>Dermatomyositis - blood</topic><topic>Dermatomyositis - diagnosis</topic><topic>Endothelium, Vascular - immunology</topic><topic>Eosinophilia - blood</topic><topic>Eosinophilia - diagnosis</topic><topic>Fasciitis - blood</topic><topic>Fasciitis - diagnosis</topic><topic>Female</topic><topic>Galectins - blood</topic><topic>Heart Disease Risk Factors</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monitoring, Immunologic - methods</topic><topic>Netherlands</topic><topic>Patient Acuity</topic><topic>Receptors, Tumor Necrosis Factor, Type II - blood</topic><topic>Scleroderma, Localized - blood</topic><topic>Scleroderma, Localized - diagnosis</topic><topic>Vascular Cell Adhesion Molecule-1 - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wienke, Judith</creatorcontrib><creatorcontrib>Mertens, Jorre S</creatorcontrib><creatorcontrib>Garcia, Samuel</creatorcontrib><creatorcontrib>Lim, Johan</creatorcontrib><creatorcontrib>Wijngaarde, Camiel A</creatorcontrib><creatorcontrib>Yeo, Joo Guan</creatorcontrib><creatorcontrib>Meyer, Alain</creatorcontrib><creatorcontrib>van den Hoogen, Lucas L</creatorcontrib><creatorcontrib>Tekstra, Janneke</creatorcontrib><creatorcontrib>Hoogendijk, Jessica E</creatorcontrib><creatorcontrib>Otten, Henny G</creatorcontrib><creatorcontrib>Fritsch-Stork, Ruth D E</creatorcontrib><creatorcontrib>de Jager, Wilco</creatorcontrib><creatorcontrib>Seyger, Marieke M B</creatorcontrib><creatorcontrib>Thurlings, Rogier M</creatorcontrib><creatorcontrib>de Jong, Elke M G J</creatorcontrib><creatorcontrib>van der Kooi, Anneke J</creatorcontrib><creatorcontrib>van der Pol, W Ludo</creatorcontrib><creatorcontrib>Arkachaisri, Thaschawee</creatorcontrib><creatorcontrib>Radstake, Timothy R D J</creatorcontrib><creatorcontrib>van Royen-Kerkhof, Annet</creatorcontrib><creatorcontrib>van Wijk, Femke</creatorcontrib><creatorcontrib>Dutch Juvenile Myositis Consortium</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>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wienke, Judith</au><au>Mertens, Jorre S</au><au>Garcia, Samuel</au><au>Lim, Johan</au><au>Wijngaarde, Camiel A</au><au>Yeo, Joo Guan</au><au>Meyer, Alain</au><au>van den Hoogen, Lucas L</au><au>Tekstra, Janneke</au><au>Hoogendijk, Jessica E</au><au>Otten, Henny G</au><au>Fritsch-Stork, Ruth D E</au><au>de Jager, Wilco</au><au>Seyger, Marieke M B</au><au>Thurlings, Rogier M</au><au>de Jong, Elke M G J</au><au>van der Kooi, Anneke J</au><au>van der Pol, W Ludo</au><au>Arkachaisri, Thaschawee</au><au>Radstake, Timothy R D J</au><au>van Royen-Kerkhof, Annet</au><au>van Wijk, Femke</au><aucorp>Dutch Juvenile Myositis Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>60</volume><issue>2</issue><spage>785</spage><epage>801</epage><pages>785-801</pages><issn>1462-0324</issn><eissn>1462-0332</eissn><abstract>Abstract
Objectives
Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD.
Methods
A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA.
Results
The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with ‘signature’ markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction.
Conclusion
CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32810267</pmid><doi>10.1093/rheumatology/keaa270</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-3835-6374</orcidid><orcidid>https://orcid.org/0000-0002-7565-1954</orcidid><orcidid>https://orcid.org/0000-0002-1387-1169</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Autoimmunity Biomarkers - blood Chemokine CXCL10 - blood Chemokine CXCL13 - blood Dermatomyositis - blood Dermatomyositis - diagnosis Endothelium, Vascular - immunology Eosinophilia - blood Eosinophilia - diagnosis Fasciitis - blood Fasciitis - diagnosis Female Galectins - blood Heart Disease Risk Factors Humans Male Middle Aged Monitoring, Immunologic - methods Netherlands Patient Acuity Receptors, Tumor Necrosis Factor, Type II - blood Scleroderma, Localized - blood Scleroderma, Localized - diagnosis Vascular Cell Adhesion Molecule-1 - blood |
| title | Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk |
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