Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus

Objective To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. Methods We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) an...

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Veröffentlicht in:Clinical rheumatology 2024, Vol.43 (1), p.501-509
Hauptverfasser: Torres-Ruiz, Jiram, Rull-Gabayet, Marina, Mejía-Domínguez, Nancy R., Carrillo-Vázquez, Daniel Alberto, Reyes-Islas, Juan Alberto, Cassiano-Quezada, Fabiola, Cuellar-Rodríguez, Jennifer, Sierra-Madero, Juan, Sánchez, Jessica Márquez, Serrano-García, Jesús Salvador, González, Alexia Esquinca, Juárez-Vega, Guillermo, Tapia-Rodríguez, Miguel, Gómez-Martín, Diana
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container_end_page 509
container_issue 1
container_start_page 501
container_title Clinical rheumatology
container_volume 43
creator Torres-Ruiz, Jiram
Rull-Gabayet, Marina
Mejía-Domínguez, Nancy R.
Carrillo-Vázquez, Daniel Alberto
Reyes-Islas, Juan Alberto
Cassiano-Quezada, Fabiola
Cuellar-Rodríguez, Jennifer
Sierra-Madero, Juan
Sánchez, Jessica Márquez
Serrano-García, Jesús Salvador
González, Alexia Esquinca
Juárez-Vega, Guillermo
Tapia-Rodríguez, Miguel
Gómez-Martín, Diana
description Objective To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. Methods We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann–Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. Results Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6–14) in comparison to that at follow-up (6 (4–8), P  = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. Conclusion Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, wh
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Methods We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann–Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. Results Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6–14) in comparison to that at follow-up (6 (4–8), P  = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. Conclusion Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.</description><identifier>ISSN: 0770-3198</identifier><identifier>EISSN: 1434-9949</identifier><identifier>DOI: 10.1007/s10067-023-06810-6</identifier><identifier>PMID: 37964076</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Confocal microscopy ; Flow cytometry ; Immune response ; Immunosuppressive agents ; Innate immunity ; Leukocytes (neutrophilic) ; Lipopolysaccharides ; Lupus ; Medicine ; Medicine &amp; Public Health ; Monocytes ; Neutrophils ; Original Article ; Phagocytes ; Phagocytosis ; Prednisone ; Prophylaxis ; Respiratory burst ; Rheumatology ; Systemic lupus erythematosus ; TLR2 protein ; Toll-like receptors</subject><ispartof>Clinical rheumatology, 2024, Vol.43 (1), p.501-509</ispartof><rights>The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-251b987d7ac387b1eaff7fd1513bee4a1a83c8dcaabf88f271432cad8aa0b9f43</citedby><cites>FETCH-LOGICAL-c375t-251b987d7ac387b1eaff7fd1513bee4a1a83c8dcaabf88f271432cad8aa0b9f43</cites><orcidid>0000-0002-1807-0045</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10067-023-06810-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10067-023-06810-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37964076$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torres-Ruiz, Jiram</creatorcontrib><creatorcontrib>Rull-Gabayet, Marina</creatorcontrib><creatorcontrib>Mejía-Domínguez, Nancy R.</creatorcontrib><creatorcontrib>Carrillo-Vázquez, Daniel Alberto</creatorcontrib><creatorcontrib>Reyes-Islas, Juan Alberto</creatorcontrib><creatorcontrib>Cassiano-Quezada, Fabiola</creatorcontrib><creatorcontrib>Cuellar-Rodríguez, Jennifer</creatorcontrib><creatorcontrib>Sierra-Madero, Juan</creatorcontrib><creatorcontrib>Sánchez, Jessica Márquez</creatorcontrib><creatorcontrib>Serrano-García, Jesús Salvador</creatorcontrib><creatorcontrib>González, Alexia Esquinca</creatorcontrib><creatorcontrib>Juárez-Vega, Guillermo</creatorcontrib><creatorcontrib>Tapia-Rodríguez, Miguel</creatorcontrib><creatorcontrib>Gómez-Martín, Diana</creatorcontrib><title>Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus</title><title>Clinical rheumatology</title><addtitle>Clin Rheumatol</addtitle><addtitle>Clin Rheumatol</addtitle><description>Objective To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. Methods We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann–Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. Results Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6–14) in comparison to that at follow-up (6 (4–8), P  = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. Conclusion Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.</description><subject>Confocal microscopy</subject><subject>Flow cytometry</subject><subject>Immune response</subject><subject>Immunosuppressive agents</subject><subject>Innate immunity</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipopolysaccharides</subject><subject>Lupus</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Monocytes</subject><subject>Neutrophils</subject><subject>Original Article</subject><subject>Phagocytes</subject><subject>Phagocytosis</subject><subject>Prednisone</subject><subject>Prophylaxis</subject><subject>Respiratory burst</subject><subject>Rheumatology</subject><subject>Systemic lupus erythematosus</subject><subject>TLR2 protein</subject><subject>Toll-like receptors</subject><issn>0770-3198</issn><issn>1434-9949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kTtvFDEUhS1ERJbAH6BAlmhohvgx60eJEl5SJJpQW3c8Nutox7PMtYn238fLBJAoaHyL851j-x5CXnH2jjOmL7GdSndMyI4pw1mnnpAN72XfWdvbp2TDtGad5Nack-eId4wxYSx_Rs6ltqpnWm3I_XXCABgo-JJ-pnKkCSkgzj5BCSO9T2VH_Q7y94A0ZVp2oY3cNJqmqeZAY83NOueTeoCSQi642vCIJUzJ0309VKRhOTb3BGXGii_IWYQ9hpeP84J8-_jh9upzd_P105er9zedl3pbOrHlgzV61OCl0QMPEKOOI99yOYTQAwcjvRk9wBCNiUK37wsPowFgg429vCBv19zDMv-oAYubEvqw30MOc0XXFsKk4lvFGvrmH_Rurktur3PCcq56IcwpUKyUX2bEJUR3WNIEy9Fx5k61uLUW12pxv2pxqpleP0bXYQrjH8vvHhogVwCb1Ha9_L37P7EPQgibMw</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Torres-Ruiz, Jiram</creator><creator>Rull-Gabayet, Marina</creator><creator>Mejía-Domínguez, Nancy R.</creator><creator>Carrillo-Vázquez, Daniel Alberto</creator><creator>Reyes-Islas, Juan Alberto</creator><creator>Cassiano-Quezada, Fabiola</creator><creator>Cuellar-Rodríguez, Jennifer</creator><creator>Sierra-Madero, Juan</creator><creator>Sánchez, Jessica Márquez</creator><creator>Serrano-García, Jesús Salvador</creator><creator>González, Alexia Esquinca</creator><creator>Juárez-Vega, Guillermo</creator><creator>Tapia-Rodríguez, Miguel</creator><creator>Gómez-Martín, Diana</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1807-0045</orcidid></search><sort><creationdate>2024</creationdate><title>Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus</title><author>Torres-Ruiz, Jiram ; Rull-Gabayet, Marina ; Mejía-Domínguez, Nancy R. ; Carrillo-Vázquez, Daniel Alberto ; Reyes-Islas, Juan Alberto ; Cassiano-Quezada, Fabiola ; Cuellar-Rodríguez, Jennifer ; Sierra-Madero, Juan ; Sánchez, Jessica Márquez ; Serrano-García, Jesús Salvador ; González, Alexia Esquinca ; Juárez-Vega, Guillermo ; Tapia-Rodríguez, Miguel ; Gómez-Martín, Diana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-251b987d7ac387b1eaff7fd1513bee4a1a83c8dcaabf88f271432cad8aa0b9f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Confocal microscopy</topic><topic>Flow cytometry</topic><topic>Immune response</topic><topic>Immunosuppressive agents</topic><topic>Innate immunity</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lipopolysaccharides</topic><topic>Lupus</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Monocytes</topic><topic>Neutrophils</topic><topic>Original Article</topic><topic>Phagocytes</topic><topic>Phagocytosis</topic><topic>Prednisone</topic><topic>Prophylaxis</topic><topic>Respiratory burst</topic><topic>Rheumatology</topic><topic>Systemic lupus erythematosus</topic><topic>TLR2 protein</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torres-Ruiz, Jiram</creatorcontrib><creatorcontrib>Rull-Gabayet, Marina</creatorcontrib><creatorcontrib>Mejía-Domínguez, Nancy R.</creatorcontrib><creatorcontrib>Carrillo-Vázquez, Daniel Alberto</creatorcontrib><creatorcontrib>Reyes-Islas, Juan Alberto</creatorcontrib><creatorcontrib>Cassiano-Quezada, Fabiola</creatorcontrib><creatorcontrib>Cuellar-Rodríguez, Jennifer</creatorcontrib><creatorcontrib>Sierra-Madero, Juan</creatorcontrib><creatorcontrib>Sánchez, Jessica Márquez</creatorcontrib><creatorcontrib>Serrano-García, Jesús Salvador</creatorcontrib><creatorcontrib>González, Alexia Esquinca</creatorcontrib><creatorcontrib>Juárez-Vega, Guillermo</creatorcontrib><creatorcontrib>Tapia-Rodríguez, Miguel</creatorcontrib><creatorcontrib>Gómez-Martín, Diana</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health &amp; 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Methods We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann–Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. Results Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6–14) in comparison to that at follow-up (6 (4–8), P  = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. Conclusion Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>37964076</pmid><doi>10.1007/s10067-023-06810-6</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1807-0045</orcidid></addata></record>
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subjects Confocal microscopy
Flow cytometry
Immune response
Immunosuppressive agents
Innate immunity
Leukocytes (neutrophilic)
Lipopolysaccharides
Lupus
Medicine
Medicine & Public Health
Monocytes
Neutrophils
Original Article
Phagocytes
Phagocytosis
Prednisone
Prophylaxis
Respiratory burst
Rheumatology
Systemic lupus erythematosus
TLR2 protein
Toll-like receptors
title Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus
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