Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes
Microparticles (MPs) are small extracellular vesicles released from apoptotic or activated cells through a blebbing process. MPs express surface molecules from their parental cells and they bind IgG to form circulating immune complexes (MP-ICs) in patients with systemic lupus erythematosus (SLE). Th...
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Veröffentlicht in: | Journal of autoimmunity 2019-08, Vol.102, p.142-149 |
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creator | Mobarrez, Fariborz Fuzzi, Enrico Gunnarsson, Iva Larsson, Anders Eketjäll, Susanna Pisetsky, David S. Svenungsson, Elisabet |
description | Microparticles (MPs) are small extracellular vesicles released from apoptotic or activated cells through a blebbing process. MPs express surface molecules from their parental cells and they bind IgG to form circulating immune complexes (MP-ICs) in patients with systemic lupus erythematosus (SLE). Through investigation of MP size, IgG expression, content of nucleic acids and mitochondrial molecules, we hypothesized that unrecognized particle populations can be identified in SLE.
We investigated 327 well-characterized SLE patients and 304 controls divided into two sets (280/280 and 47/24). We measured MPs by flow cytometry using a gating strategy to encompass small (0.2–0.7 μm) and large (0.7–3.0 μm) MPs. Nucleic acids were labeled with SYTO 13 and mitochondria with MitoTracker. Expression of mitochondria markers TOM-20 and Hexokinase 1 and the presence of IgG was investigated.
MPs staining with SYTO 13 were more frequent in 280 SLE patients compared to 280 controls. In 47 SLE patients, levels of large MPs were elevated compared to 24 controls. The majority of large MPs contained mitochondria (mitoMPs). The number of mitoMPs associated positively with high disease activity, anti-dsDNA antibodies and pro-inflammatory cytokines. Patients with active lupus nephritis had higher levels of mitoMPs and IgG-positive mitoMPs.
Blood of patients with SLE contain a previously unrecognized population of circulating large MPs with bound IgG and mitochondrial proteins. Levels of these particles are related to several measures of active SLE, suggesting that these structures may have a role in disease pathogenesis.
•Blood in SLE shows increased levels of microparticles containing nucleic acids.•Microparticles in SLE display IgG as well as nucleic acids.•A sub-population of microparticles in SLE is larger in size than 0.7 μm.•The majority of the large microparticles contain mitochondrial molecules.•The level of microparticles with mitochondria is associated with features of SLE. |
doi_str_mv | 10.1016/j.jaut.2019.05.003 |
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We investigated 327 well-characterized SLE patients and 304 controls divided into two sets (280/280 and 47/24). We measured MPs by flow cytometry using a gating strategy to encompass small (0.2–0.7 μm) and large (0.7–3.0 μm) MPs. Nucleic acids were labeled with SYTO 13 and mitochondria with MitoTracker. Expression of mitochondria markers TOM-20 and Hexokinase 1 and the presence of IgG was investigated.
MPs staining with SYTO 13 were more frequent in 280 SLE patients compared to 280 controls. In 47 SLE patients, levels of large MPs were elevated compared to 24 controls. The majority of large MPs contained mitochondria (mitoMPs). The number of mitoMPs associated positively with high disease activity, anti-dsDNA antibodies and pro-inflammatory cytokines. Patients with active lupus nephritis had higher levels of mitoMPs and IgG-positive mitoMPs.
Blood of patients with SLE contain a previously unrecognized population of circulating large MPs with bound IgG and mitochondrial proteins. Levels of these particles are related to several measures of active SLE, suggesting that these structures may have a role in disease pathogenesis.
•Blood in SLE shows increased levels of microparticles containing nucleic acids.•Microparticles in SLE display IgG as well as nucleic acids.•A sub-population of microparticles in SLE is larger in size than 0.7 μm.•The majority of the large microparticles contain mitochondrial molecules.•The level of microparticles with mitochondria is associated with features of SLE.</description><identifier>ISSN: 0896-8411</identifier><identifier>ISSN: 1095-9157</identifier><identifier>EISSN: 1095-9157</identifier><identifier>DOI: 10.1016/j.jaut.2019.05.003</identifier><identifier>PMID: 31103269</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Microparticles ; Microvesicles ; Mitochondria ; Systemic lupus erythematosus</subject><ispartof>Journal of autoimmunity, 2019-08, Vol.102, p.142-149</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-9cb3b95aa3bdc5be3a7c1809efe3ec51ec8d10c1a7ebcabce0d0259dfe5e79453</citedby><cites>FETCH-LOGICAL-c431t-9cb3b95aa3bdc5be3a7c1809efe3ec51ec8d10c1a7ebcabce0d0259dfe5e79453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S089684111930099X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31103269$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-385064$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:141596521$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Mobarrez, Fariborz</creatorcontrib><creatorcontrib>Fuzzi, Enrico</creatorcontrib><creatorcontrib>Gunnarsson, Iva</creatorcontrib><creatorcontrib>Larsson, Anders</creatorcontrib><creatorcontrib>Eketjäll, Susanna</creatorcontrib><creatorcontrib>Pisetsky, David S.</creatorcontrib><creatorcontrib>Svenungsson, Elisabet</creatorcontrib><title>Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes</title><title>Journal of autoimmunity</title><addtitle>J Autoimmun</addtitle><description>Microparticles (MPs) are small extracellular vesicles released from apoptotic or activated cells through a blebbing process. MPs express surface molecules from their parental cells and they bind IgG to form circulating immune complexes (MP-ICs) in patients with systemic lupus erythematosus (SLE). Through investigation of MP size, IgG expression, content of nucleic acids and mitochondrial molecules, we hypothesized that unrecognized particle populations can be identified in SLE.
We investigated 327 well-characterized SLE patients and 304 controls divided into two sets (280/280 and 47/24). We measured MPs by flow cytometry using a gating strategy to encompass small (0.2–0.7 μm) and large (0.7–3.0 μm) MPs. Nucleic acids were labeled with SYTO 13 and mitochondria with MitoTracker. Expression of mitochondria markers TOM-20 and Hexokinase 1 and the presence of IgG was investigated.
MPs staining with SYTO 13 were more frequent in 280 SLE patients compared to 280 controls. In 47 SLE patients, levels of large MPs were elevated compared to 24 controls. The majority of large MPs contained mitochondria (mitoMPs). The number of mitoMPs associated positively with high disease activity, anti-dsDNA antibodies and pro-inflammatory cytokines. Patients with active lupus nephritis had higher levels of mitoMPs and IgG-positive mitoMPs.
Blood of patients with SLE contain a previously unrecognized population of circulating large MPs with bound IgG and mitochondrial proteins. Levels of these particles are related to several measures of active SLE, suggesting that these structures may have a role in disease pathogenesis.
•Blood in SLE shows increased levels of microparticles containing nucleic acids.•Microparticles in SLE display IgG as well as nucleic acids.•A sub-population of microparticles in SLE is larger in size than 0.7 μm.•The majority of the large microparticles contain mitochondrial molecules.•The level of microparticles with mitochondria is associated with features of SLE.</description><subject>Microparticles</subject><subject>Microvesicles</subject><subject>Mitochondria</subject><subject>Systemic lupus erythematosus</subject><issn>0896-8411</issn><issn>1095-9157</issn><issn>1095-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kctu1DAUQC0EokPhB1ggL1k0wY7jJEZsqtIC0iAWBbaWHzcdD0kcbIcWvr6OZugOVrbsc8_iHoReUlJSQps3-3KvllRWhIqS8JIQ9ghtKBG8EJS3j9GGdKIpuprSE_Qsxj0hlHLOn6ITRilhVSM26O6zM8HPKiRnBojYTTjtAOvBe4t9j2eVHEwp4luXdvh6e_kWX7s_cIaNn1L-WJnRJW92frLBKawmi4MfYDUZF8wyZMN0g904LhPksXEe4A7ic_SkV0OEF8fzFH27uvx68bHYfvnw6eJ8W5ia0VQIo5kWXCmmreEamGoN7YiAHhgYTsF0lhJDVQvaKG2AWFJxYXvg0Iqas1NUHLzxFuZFyzm4UYXf0isnj08_8g1k3Yq2Wvmzf_Lv3fdz6cONXBbJOk6aOuOvD_gc_M8FYpKjiwaGQU3glyirilWkqWjbZbQ6oHnhMQboH9yUyDWo3Ms1qFyDSsJlDpqHXh39ix7BPoz8LZiBdwcA8hJ_OQgymlzMgHUBTJLWu__57wFZgrVt</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Mobarrez, Fariborz</creator><creator>Fuzzi, Enrico</creator><creator>Gunnarsson, Iva</creator><creator>Larsson, Anders</creator><creator>Eketjäll, Susanna</creator><creator>Pisetsky, David S.</creator><creator>Svenungsson, Elisabet</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF2</scope></search><sort><creationdate>20190801</creationdate><title>Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes</title><author>Mobarrez, Fariborz ; Fuzzi, Enrico ; Gunnarsson, Iva ; Larsson, Anders ; Eketjäll, Susanna ; Pisetsky, David S. ; Svenungsson, Elisabet</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-9cb3b95aa3bdc5be3a7c1809efe3ec51ec8d10c1a7ebcabce0d0259dfe5e79453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Microparticles</topic><topic>Microvesicles</topic><topic>Mitochondria</topic><topic>Systemic lupus erythematosus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mobarrez, Fariborz</creatorcontrib><creatorcontrib>Fuzzi, Enrico</creatorcontrib><creatorcontrib>Gunnarsson, Iva</creatorcontrib><creatorcontrib>Larsson, Anders</creatorcontrib><creatorcontrib>Eketjäll, Susanna</creatorcontrib><creatorcontrib>Pisetsky, David S.</creatorcontrib><creatorcontrib>Svenungsson, Elisabet</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Uppsala universitet</collection><jtitle>Journal of autoimmunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mobarrez, Fariborz</au><au>Fuzzi, Enrico</au><au>Gunnarsson, Iva</au><au>Larsson, Anders</au><au>Eketjäll, Susanna</au><au>Pisetsky, David S.</au><au>Svenungsson, Elisabet</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes</atitle><jtitle>Journal of autoimmunity</jtitle><addtitle>J Autoimmun</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>102</volume><spage>142</spage><epage>149</epage><pages>142-149</pages><issn>0896-8411</issn><issn>1095-9157</issn><eissn>1095-9157</eissn><abstract>Microparticles (MPs) are small extracellular vesicles released from apoptotic or activated cells through a blebbing process. MPs express surface molecules from their parental cells and they bind IgG to form circulating immune complexes (MP-ICs) in patients with systemic lupus erythematosus (SLE). Through investigation of MP size, IgG expression, content of nucleic acids and mitochondrial molecules, we hypothesized that unrecognized particle populations can be identified in SLE.
We investigated 327 well-characterized SLE patients and 304 controls divided into two sets (280/280 and 47/24). We measured MPs by flow cytometry using a gating strategy to encompass small (0.2–0.7 μm) and large (0.7–3.0 μm) MPs. Nucleic acids were labeled with SYTO 13 and mitochondria with MitoTracker. Expression of mitochondria markers TOM-20 and Hexokinase 1 and the presence of IgG was investigated.
MPs staining with SYTO 13 were more frequent in 280 SLE patients compared to 280 controls. In 47 SLE patients, levels of large MPs were elevated compared to 24 controls. The majority of large MPs contained mitochondria (mitoMPs). The number of mitoMPs associated positively with high disease activity, anti-dsDNA antibodies and pro-inflammatory cytokines. Patients with active lupus nephritis had higher levels of mitoMPs and IgG-positive mitoMPs.
Blood of patients with SLE contain a previously unrecognized population of circulating large MPs with bound IgG and mitochondrial proteins. Levels of these particles are related to several measures of active SLE, suggesting that these structures may have a role in disease pathogenesis.
•Blood in SLE shows increased levels of microparticles containing nucleic acids.•Microparticles in SLE display IgG as well as nucleic acids.•A sub-population of microparticles in SLE is larger in size than 0.7 μm.•The majority of the large microparticles contain mitochondrial molecules.•The level of microparticles with mitochondria is associated with features of SLE.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31103269</pmid><doi>10.1016/j.jaut.2019.05.003</doi><tpages>8</tpages></addata></record> |
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subjects | Microparticles Microvesicles Mitochondria Systemic lupus erythematosus |
title | Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes |
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