Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus
Background Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was t...
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| Veröffentlicht in: | International journal of rheumatic diseases 2014-09, Vol.17 (7), p.790-795 |
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| creator | Tselios, Konstantinos Sarantopoulos, Alexandros Gkougkourelas, Ioannis Papagianni, Aikaterini Boura, Panagiota |
| description | Background
Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.
Patients and Methods
Ten Caucasian lupus patients were included, six with LN classes IV–V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m2/month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4+CD25highFOXP3+ Tregs were assessed by flow‐cytometry at baseline and before every subsequent pulse and 3–6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).
Results
In LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P |
| doi_str_mv | 10.1111/1756-185X.12500 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1628882635</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1628882635</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4790-21686784590062d0123202aa822531b09dbea2b94df6079aec383bb913d2e94b3</originalsourceid><addsrcrecordid>eNqFkc1v1DAQxS0EomXhzA1Z4sIlrT_iODlWq35JK-ihCNSL5TizjUsSBzum5Nj_vE633QMXfLE183tPnnkIfaTkiKZzTKUoMlqKn0eUCUJeocN95fX-ndMD9C6EO0IKygv5Fh0wkXMiKn6IHi4H40EHwG6LR_B2bMHrDl9jD7ex05PzMzbQdQE30dvhNtV7G4J1A7ZDE820vO7t1GIzm86NrQtjq3vbQOpjnfp_AIc5TElmcBfHGDD4eWqhT-YhhvfozVZ3AT483yv0_ez0en2Rbb6dX65PNpnJZUUyRouykGUuqjQGawhlnBGmdcmY4LQmVVODZnWVN9uCyEqD4SWv64ryhkGV13yFvux8R-9-RwiTSnMsk-kBXAyKFqwsS1ZwkdDP_6B3Lvoh_e6J4jInyXyFjneU8S4ED1s1ettrPytK1JKOWvavlizUUzpJ8enZN9Y9NHv-JY4EiB1wbzuY_-enTq42L8bZTmfTnv_uddr_UoXkUqgfX8_VzZnckPXVhbrhj3PJqn0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1628374038</pqid></control><display><type>article</type><title>Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Tselios, Konstantinos ; Sarantopoulos, Alexandros ; Gkougkourelas, Ioannis ; Papagianni, Aikaterini ; Boura, Panagiota</creator><creatorcontrib>Tselios, Konstantinos ; Sarantopoulos, Alexandros ; Gkougkourelas, Ioannis ; Papagianni, Aikaterini ; Boura, Panagiota</creatorcontrib><description>Background
Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.
Patients and Methods
Ten Caucasian lupus patients were included, six with LN classes IV–V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m2/month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4+CD25highFOXP3+ Tregs were assessed by flow‐cytometry at baseline and before every subsequent pulse and 3–6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).
Results
In LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients.
Conclusions
Cyclophosphamide pulse therapy was associated with a significant increase of the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.</description><identifier>ISSN: 1756-1841</identifier><identifier>EISSN: 1756-185X</identifier><identifier>DOI: 10.1111/1756-185X.12500</identifier><identifier>PMID: 25430593</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Biomarkers - blood ; cyclophosphamide ; Cyclophosphamide - administration & dosage ; Female ; Forkhead Transcription Factors - blood ; Humans ; Immunologic Factors - administration & dosage ; Interleukin-2 Receptor alpha Subunit - blood ; Lupus Erythematosus, Systemic - blood ; Lupus Erythematosus, Systemic - diagnosis ; Lupus Erythematosus, Systemic - drug therapy ; Lupus Erythematosus, Systemic - immunology ; Lupus Nephritis - blood ; Lupus Nephritis - diagnosis ; Lupus Nephritis - drug therapy ; Lupus Nephritis - immunology ; Lupus Vasculitis, Central Nervous System - blood ; Lupus Vasculitis, Central Nervous System - diagnosis ; Lupus Vasculitis, Central Nervous System - drug therapy ; Lupus Vasculitis, Central Nervous System - immunology ; Male ; Pulse Therapy, Drug ; Remission Induction ; systemic lupus erythematosus ; T regulatory cells ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Time Factors ; Treatment Outcome ; Up-Regulation</subject><ispartof>International journal of rheumatic diseases, 2014-09, Vol.17 (7), p.790-795</ispartof><rights>2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd</rights><rights>2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.</rights><rights>International Journal of Rheumatic Diseases © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4790-21686784590062d0123202aa822531b09dbea2b94df6079aec383bb913d2e94b3</citedby><cites>FETCH-LOGICAL-c4790-21686784590062d0123202aa822531b09dbea2b94df6079aec383bb913d2e94b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1756-185X.12500$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1756-185X.12500$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25430593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tselios, Konstantinos</creatorcontrib><creatorcontrib>Sarantopoulos, Alexandros</creatorcontrib><creatorcontrib>Gkougkourelas, Ioannis</creatorcontrib><creatorcontrib>Papagianni, Aikaterini</creatorcontrib><creatorcontrib>Boura, Panagiota</creatorcontrib><title>Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus</title><title>International journal of rheumatic diseases</title><addtitle>Int J Rheum Dis</addtitle><description>Background
Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.
Patients and Methods
Ten Caucasian lupus patients were included, six with LN classes IV–V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m2/month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4+CD25highFOXP3+ Tregs were assessed by flow‐cytometry at baseline and before every subsequent pulse and 3–6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).
Results
In LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients.
Conclusions
Cyclophosphamide pulse therapy was associated with a significant increase of the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.</description><subject>Adult</subject><subject>Biomarkers - blood</subject><subject>cyclophosphamide</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Female</subject><subject>Forkhead Transcription Factors - blood</subject><subject>Humans</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Interleukin-2 Receptor alpha Subunit - blood</subject><subject>Lupus Erythematosus, Systemic - blood</subject><subject>Lupus Erythematosus, Systemic - diagnosis</subject><subject>Lupus Erythematosus, Systemic - drug therapy</subject><subject>Lupus Erythematosus, Systemic - immunology</subject><subject>Lupus Nephritis - blood</subject><subject>Lupus Nephritis - diagnosis</subject><subject>Lupus Nephritis - drug therapy</subject><subject>Lupus Nephritis - immunology</subject><subject>Lupus Vasculitis, Central Nervous System - blood</subject><subject>Lupus Vasculitis, Central Nervous System - diagnosis</subject><subject>Lupus Vasculitis, Central Nervous System - drug therapy</subject><subject>Lupus Vasculitis, Central Nervous System - immunology</subject><subject>Male</subject><subject>Pulse Therapy, Drug</subject><subject>Remission Induction</subject><subject>systemic lupus erythematosus</subject><subject>T regulatory cells</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Up-Regulation</subject><issn>1756-1841</issn><issn>1756-185X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EomXhzA1Z4sIlrT_iODlWq35JK-ihCNSL5TizjUsSBzum5Nj_vE633QMXfLE183tPnnkIfaTkiKZzTKUoMlqKn0eUCUJeocN95fX-ndMD9C6EO0IKygv5Fh0wkXMiKn6IHi4H40EHwG6LR_B2bMHrDl9jD7ex05PzMzbQdQE30dvhNtV7G4J1A7ZDE820vO7t1GIzm86NrQtjq3vbQOpjnfp_AIc5TElmcBfHGDD4eWqhT-YhhvfozVZ3AT483yv0_ez0en2Rbb6dX65PNpnJZUUyRouykGUuqjQGawhlnBGmdcmY4LQmVVODZnWVN9uCyEqD4SWv64ryhkGV13yFvux8R-9-RwiTSnMsk-kBXAyKFqwsS1ZwkdDP_6B3Lvoh_e6J4jInyXyFjneU8S4ED1s1ettrPytK1JKOWvavlizUUzpJ8enZN9Y9NHv-JY4EiB1wbzuY_-enTq42L8bZTmfTnv_uddr_UoXkUqgfX8_VzZnckPXVhbrhj3PJqn0</recordid><startdate>201409</startdate><enddate>201409</enddate><creator>Tselios, Konstantinos</creator><creator>Sarantopoulos, Alexandros</creator><creator>Gkougkourelas, Ioannis</creator><creator>Papagianni, Aikaterini</creator><creator>Boura, Panagiota</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201409</creationdate><title>Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus</title><author>Tselios, Konstantinos ; Sarantopoulos, Alexandros ; Gkougkourelas, Ioannis ; Papagianni, Aikaterini ; Boura, Panagiota</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4790-21686784590062d0123202aa822531b09dbea2b94df6079aec383bb913d2e94b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Biomarkers - blood</topic><topic>cyclophosphamide</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Female</topic><topic>Forkhead Transcription Factors - blood</topic><topic>Humans</topic><topic>Immunologic Factors - administration & dosage</topic><topic>Interleukin-2 Receptor alpha Subunit - blood</topic><topic>Lupus Erythematosus, Systemic - blood</topic><topic>Lupus Erythematosus, Systemic - diagnosis</topic><topic>Lupus Erythematosus, Systemic - drug therapy</topic><topic>Lupus Erythematosus, Systemic - immunology</topic><topic>Lupus Nephritis - blood</topic><topic>Lupus Nephritis - diagnosis</topic><topic>Lupus Nephritis - drug therapy</topic><topic>Lupus Nephritis - immunology</topic><topic>Lupus Vasculitis, Central Nervous System - blood</topic><topic>Lupus Vasculitis, Central Nervous System - diagnosis</topic><topic>Lupus Vasculitis, Central Nervous System - drug therapy</topic><topic>Lupus Vasculitis, Central Nervous System - immunology</topic><topic>Male</topic><topic>Pulse Therapy, Drug</topic><topic>Remission Induction</topic><topic>systemic lupus erythematosus</topic><topic>T regulatory cells</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tselios, Konstantinos</creatorcontrib><creatorcontrib>Sarantopoulos, Alexandros</creatorcontrib><creatorcontrib>Gkougkourelas, Ioannis</creatorcontrib><creatorcontrib>Papagianni, Aikaterini</creatorcontrib><creatorcontrib>Boura, Panagiota</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tselios, Konstantinos</au><au>Sarantopoulos, Alexandros</au><au>Gkougkourelas, Ioannis</au><au>Papagianni, Aikaterini</au><au>Boura, Panagiota</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus</atitle><jtitle>International journal of rheumatic diseases</jtitle><addtitle>Int J Rheum Dis</addtitle><date>2014-09</date><risdate>2014</risdate><volume>17</volume><issue>7</issue><spage>790</spage><epage>795</epage><pages>790-795</pages><issn>1756-1841</issn><eissn>1756-185X</eissn><abstract>Background
Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.
Patients and Methods
Ten Caucasian lupus patients were included, six with LN classes IV–V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m2/month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4+CD25highFOXP3+ Tregs were assessed by flow‐cytometry at baseline and before every subsequent pulse and 3–6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).
Results
In LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients.
Conclusions
Cyclophosphamide pulse therapy was associated with a significant increase of the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25430593</pmid><doi>10.1111/1756-185X.12500</doi><tpages>6</tpages></addata></record> |
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| ispartof | International journal of rheumatic diseases, 2014-09, Vol.17 (7), p.790-795 |
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| subjects | Adult Biomarkers - blood cyclophosphamide Cyclophosphamide - administration & dosage Female Forkhead Transcription Factors - blood Humans Immunologic Factors - administration & dosage Interleukin-2 Receptor alpha Subunit - blood Lupus Erythematosus, Systemic - blood Lupus Erythematosus, Systemic - diagnosis Lupus Erythematosus, Systemic - drug therapy Lupus Erythematosus, Systemic - immunology Lupus Nephritis - blood Lupus Nephritis - diagnosis Lupus Nephritis - drug therapy Lupus Nephritis - immunology Lupus Vasculitis, Central Nervous System - blood Lupus Vasculitis, Central Nervous System - diagnosis Lupus Vasculitis, Central Nervous System - drug therapy Lupus Vasculitis, Central Nervous System - immunology Male Pulse Therapy, Drug Remission Induction systemic lupus erythematosus T regulatory cells T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Time Factors Treatment Outcome Up-Regulation |
| title | Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus |
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