CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients
Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping...
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creator | Marques, Claudia Diniz Lopes Duarte, Angela Luzia Branco Pinto de Melo Rego, Moacyr Jesus Barreto Pitta, Maira Galdino da Rocha Romano, Audrey Pereira, Michelly Cristiny Vasconcelos, Viviane F. de Arruda, Rodrigo Gomes de Mariz, Henrique de Ataide Chagas, Mardonny B. O. Brelaz, Maria Carolina Accioly Silva-Neta, Helena L. Pitta, Ivan da Rocha |
description | Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+ F O X P 3 h i g h CD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+ F O X P 3 l o w CD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE. |
doi_str_mv | 10.1155/2018/3419565 |
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O. ; Brelaz, Maria Carolina Accioly ; Silva-Neta, Helena L. ; Pitta, Ivan da Rocha</creator><contributor>Mahler, Michael ; Michael Mahler</contributor><creatorcontrib>Marques, Claudia Diniz Lopes ; Duarte, Angela Luzia Branco Pinto ; de Melo Rego, Moacyr Jesus Barreto ; Pitta, Maira Galdino da Rocha ; Romano, Audrey ; Pereira, Michelly Cristiny ; Vasconcelos, Viviane F. de ; Arruda, Rodrigo Gomes de ; Mariz, Henrique de Ataide ; Chagas, Mardonny B. O. ; Brelaz, Maria Carolina Accioly ; Silva-Neta, Helena L. ; Pitta, Ivan da Rocha ; Mahler, Michael ; Michael Mahler</creatorcontrib><description>Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+ F O X P 3 h i g h CD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+ F O X P 3 l o w CD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2018/3419565</identifier><identifier>PMID: 30009168</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Autoimmune diseases ; Bioindicators ; Biomarkers ; Biomedical research ; CD25 antigen ; CD4 antigen ; CD45 antigen ; CD45RA antigen ; Chronic conditions ; Diabetes ; Disease ; Foxp3 protein ; Genotype & phenotype ; Immunoregulation ; Investigations ; Laboratories ; Leukocytes (mononuclear) ; Lupus ; Lymphocytes ; Lymphocytes T ; Patients ; Peripheral blood mononuclear cells ; Phenotypes ; Regression analysis ; Remission ; Rheumatology ; Systemic lupus erythematosus</subject><ispartof>BioMed research international, 2018-01, Vol.2018 (2018), p.1-8</ispartof><rights>Copyright © 2018 Helena L. Silva-Neta et al.</rights><rights>Copyright © 2018 Helena L. Silva-Neta et al.; This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2018 Helena L. Silva-Neta et al. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-5881-0338 ; 0000-0002-1672-8202 ; 0000-0003-2205-0618 ; 0000-0002-1883-6012</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020667/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020667/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids></links><search><contributor>Mahler, Michael</contributor><contributor>Michael Mahler</contributor><creatorcontrib>Marques, Claudia Diniz Lopes</creatorcontrib><creatorcontrib>Duarte, Angela Luzia Branco Pinto</creatorcontrib><creatorcontrib>de Melo Rego, Moacyr Jesus Barreto</creatorcontrib><creatorcontrib>Pitta, Maira Galdino da Rocha</creatorcontrib><creatorcontrib>Romano, Audrey</creatorcontrib><creatorcontrib>Pereira, Michelly Cristiny</creatorcontrib><creatorcontrib>Vasconcelos, Viviane F. de</creatorcontrib><creatorcontrib>Arruda, Rodrigo Gomes de</creatorcontrib><creatorcontrib>Mariz, Henrique de Ataide</creatorcontrib><creatorcontrib>Chagas, Mardonny B. O.</creatorcontrib><creatorcontrib>Brelaz, Maria Carolina Accioly</creatorcontrib><creatorcontrib>Silva-Neta, Helena L.</creatorcontrib><creatorcontrib>Pitta, Ivan da Rocha</creatorcontrib><title>CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients</title><title>BioMed research international</title><description>Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+ F O X P 3 h i g h CD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+ F O X P 3 l o w CD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.</description><subject>Autoimmune diseases</subject><subject>Bioindicators</subject><subject>Biomarkers</subject><subject>Biomedical research</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>CD45 antigen</subject><subject>CD45RA antigen</subject><subject>Chronic conditions</subject><subject>Diabetes</subject><subject>Disease</subject><subject>Foxp3 protein</subject><subject>Genotype & phenotype</subject><subject>Immunoregulation</subject><subject>Investigations</subject><subject>Laboratories</subject><subject>Leukocytes (mononuclear)</subject><subject>Lupus</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phenotypes</subject><subject>Regression analysis</subject><subject>Remission</subject><subject>Rheumatology</subject><subject>Systemic lupus erythematosus</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkd9qFDEUxoMottTeeS0Bb4SyNn8mmcyNsN22Kix0qRW8C5mZk27qzGRNMi3jC-i1j-iTmGWXigbCySE_vuR8H0IvKXlLqRCnjFB1ygtaCSmeoEPGaTGTtKBPH8-cH6DjGO9IXopKUsnn6IDnpqJSHaIfi_PiJG9xPf_989fl1ZcV7_wDvobbsTPJhwnf4AV0XcQm4pVPMCRnOnzmfG_CVwgRe4vPXQQTAc-b5O5dmrAb8KcpJuhdg5fjZoz4IkxpDX2WjLk7C-a765wZ8MoklzXjC_TMmi7C8b4eoc-XFzeLD7Pl1fuPi_lyBrQU5czWjRACyrasKk5b2UBtKsUqbgmYWgrFDWvqsmaWglW2bBnhStRK1lbkyvkRerfT3Yx1D22T3w6m05vg8jyT9sbpf28Gt9a3_l5LwoiUZRZ4sxcI_tsIMenexSY7ZAbwY9SMlEQRKajM6Ov_0Ds_hiGPlymhKsIKvhU82VFrN7TmwT3-hRK9zVhvM9b7jDP9akdnLwNY85emTGxN-QMBCaLK</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Marques, Claudia Diniz Lopes</creator><creator>Duarte, Angela Luzia Branco Pinto</creator><creator>de Melo Rego, Moacyr Jesus Barreto</creator><creator>Pitta, Maira Galdino da Rocha</creator><creator>Romano, Audrey</creator><creator>Pereira, Michelly Cristiny</creator><creator>Vasconcelos, Viviane F. de</creator><creator>Arruda, Rodrigo Gomes de</creator><creator>Mariz, Henrique de Ataide</creator><creator>Chagas, Mardonny B. 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O.</au><au>Brelaz, Maria Carolina Accioly</au><au>Silva-Neta, Helena L.</au><au>Pitta, Ivan da Rocha</au><au>Mahler, Michael</au><au>Michael Mahler</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients</atitle><jtitle>BioMed research international</jtitle><date>2018-01-01</date><risdate>2018</risdate><volume>2018</volume><issue>2018</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+ F O X P 3 h i g h CD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+ F O X P 3 l o w CD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>30009168</pmid><doi>10.1155/2018/3419565</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5881-0338</orcidid><orcidid>https://orcid.org/0000-0002-1672-8202</orcidid><orcidid>https://orcid.org/0000-0003-2205-0618</orcidid><orcidid>https://orcid.org/0000-0002-1883-6012</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Autoimmune diseases Bioindicators Biomarkers Biomedical research CD25 antigen CD4 antigen CD45 antigen CD45RA antigen Chronic conditions Diabetes Disease Foxp3 protein Genotype & phenotype Immunoregulation Investigations Laboratories Leukocytes (mononuclear) Lupus Lymphocytes Lymphocytes T Patients Peripheral blood mononuclear cells Phenotypes Regression analysis Remission Rheumatology Systemic lupus erythematosus |
title | CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients |
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