Checkpoints for Autoreactive B Cells in the Peripheral Blood of Lupus Patients Assessed by Flow Cytometry

Objective Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there ha...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Arthritis & rheumatology (Hoboken, N.J.) Jg. 68; H. 9; S. 2210 - 2220
Hauptverfasser:	Malkiel, Susan, Jeganathan, Venkatesh, Wolfson, Stacey, Manjarrez Orduño, Nataly, Marasco, Emiliano, Aranow, Cynthia, Mackay, Meggan, Gregersen, Peter K., Diamond, Betty
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Wiley Subscription Services, Inc 01.09.2016
Schlagworte:	Adult B-Lymphocytes - immunology Female Flow Cytometry Humans Immune Tolerance Lupus Lupus Erythematosus, Systemic - blood Lymphocyte receptors Male Middle Aged T cell receptors
ISSN:	2326-5191, 2326-5205
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Abstract	Objective Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there has been no convenient assay with which to measure the frequency of circulating B cells that recognize nuclear antigens (ANA+ B cells) in patients. The aim of this study was to generate an assay to easily identify these B cells and to examine its utility in a study of autoreactive B cells in systemic lupus erythematosus (SLE). Methods We developed and validated a novel flow cytometry–based assay that identifies ANA+ B cells using biotinylated nuclear extracts, and utilized it to examine B cell tolerance checkpoints in peripheral blood mononuclear cells obtained from SLE patients and healthy controls. Results We observed progressive selection against ANA+ B cells as they matured from transitional to naive to CD27+IgD− and CD27+IgD+ memory cells in both healthy subjects and SLE patients; however, ANA+ naive B cells in SLE patients were not anergized to the same extent as in healthy individuals. We also showed that anergy induction is restored in SLE patients treated with belimumab, an inhibitor of BAFF. Conclusion This assay will enable studies of large populations to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in healthy subjects and patients with autoimmune disease and permit monitoring of the B cell response to therapeutic interventions.
AbstractList	Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there has been no convenient assay with which to measure the frequency of circulating B cells that recognize nuclear antigens (ANA+ B cells) in patients. The aim of this study was to generate an assay to easily identify these B cells and to examine its utility in a study of autoreactive B cells in systemic lupus erythematosus (SLE). We developed and validated a novel flow cytometry-based assay that identifies ANA+ B cells using biotinylated nuclear extracts, and utilized it to examine B cell tolerance checkpoints in peripheral blood mononuclear cells obtained from SLE patients and healthy controls. We observed progressive selection against ANA+ B cells as they matured from transitional to naive to CD27+IgD- and CD27+IgD+ memory cells in both healthy subjects and SLE patients; however, ANA+ naive B cells in SLE patients were not anergized to the same extent as in healthy individuals. We also showed that anergy induction is restored in SLE patients treated with belimumab, an inhibitor of BAFF. This assay will enable studies of large populations to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in healthy subjects and patients with autoimmune disease and permit monitoring of the B cell response to therapeutic interventions. Objective Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there has been no convenient assay with which to measure the frequency of circulating B cells that recognize nuclear antigens (ANA+ B cells) in patients. The aim of this study was to generate an assay to easily identify these B cells and to examine its utility in a study of autoreactive B cells in systemic lupus erythematosus (SLE). Methods We developed and validated a novel flow cytometry-based assay that identifies ANA+ B cells using biotinylated nuclear extracts, and utilized it to examine B cell tolerance checkpoints in peripheral blood mononuclear cells obtained from SLE patients and healthy controls. Results We observed progressive selection against ANA+ B cells as they matured from transitional to naive to CD27+IgD- and CD27+IgD+ memory cells in both healthy subjects and SLE patients; however, ANA+ naive B cells in SLE patients were not anergized to the same extent as in healthy individuals. We also showed that anergy induction is restored in SLE patients treated with belimumab, an inhibitor of BAFF. Conclusion This assay will enable studies of large populations to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in healthy subjects and patients with autoimmune disease and permit monitoring of the B cell response to therapeutic interventions. OBJECTIVEAntinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there has been no convenient assay with which to measure the frequency of circulating B cells that recognize nuclear antigens (ANA+ B cells) in patients. The aim of this study was to generate an assay to easily identify these B cells and to examine its utility in a study of autoreactive B cells in systemic lupus erythematosus (SLE).METHODSWe developed and validated a novel flow cytometry-based assay that identifies ANA+ B cells using biotinylated nuclear extracts, and utilized it to examine B cell tolerance checkpoints in peripheral blood mononuclear cells obtained from SLE patients and healthy controls.RESULTSWe observed progressive selection against ANA+ B cells as they matured from transitional to naive to CD27+IgD- and CD27+IgD+ memory cells in both healthy subjects and SLE patients; however, ANA+ naive B cells in SLE patients were not anergized to the same extent as in healthy individuals. We also showed that anergy induction is restored in SLE patients treated with belimumab, an inhibitor of BAFF.CONCLUSIONThis assay will enable studies of large populations to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in healthy subjects and patients with autoimmune disease and permit monitoring of the B cell response to therapeutic interventions. Objective Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there has been no convenient assay with which to measure the frequency of circulating B cells that recognize nuclear antigens (ANA+ B cells) in patients. The aim of this study was to generate an assay to easily identify these B cells and to examine its utility in a study of autoreactive B cells in systemic lupus erythematosus (SLE). Methods We developed and validated a novel flow cytometry–based assay that identifies ANA+ B cells using biotinylated nuclear extracts, and utilized it to examine B cell tolerance checkpoints in peripheral blood mononuclear cells obtained from SLE patients and healthy controls. Results We observed progressive selection against ANA+ B cells as they matured from transitional to naive to CD27+IgD− and CD27+IgD+ memory cells in both healthy subjects and SLE patients; however, ANA+ naive B cells in SLE patients were not anergized to the same extent as in healthy individuals. We also showed that anergy induction is restored in SLE patients treated with belimumab, an inhibitor of BAFF. Conclusion This assay will enable studies of large populations to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in healthy subjects and patients with autoimmune disease and permit monitoring of the B cell response to therapeutic interventions.
Author	Aranow, Cynthia Gregersen, Peter K. Diamond, Betty Jeganathan, Venkatesh Wolfson, Stacey Malkiel, Susan Mackay, Meggan Marasco, Emiliano Manjarrez Orduño, Nataly
Author_xml	– sequence: 1 givenname: Susan surname: Malkiel fullname: Malkiel, Susan – sequence: 2 givenname: Venkatesh surname: Jeganathan fullname: Jeganathan, Venkatesh – sequence: 3 givenname: Stacey surname: Wolfson fullname: Wolfson, Stacey – sequence: 4 givenname: Nataly surname: Manjarrez Orduño fullname: Manjarrez Orduño, Nataly – sequence: 5 givenname: Emiliano surname: Marasco fullname: Marasco, Emiliano – sequence: 6 givenname: Cynthia surname: Aranow fullname: Aranow, Cynthia organization: Feinstein Institute for Medical Research, Northwell Health – sequence: 7 givenname: Meggan surname: Mackay fullname: Mackay, Meggan organization: Feinstein Institute for Medical Research, Northwell Health – sequence: 8 givenname: Peter K. surname: Gregersen fullname: Gregersen, Peter K. organization: Feinstein Institute for Medical Research, Northwell Health – sequence: 9 givenname: Betty surname: Diamond fullname: Diamond, Betty organization: Feinstein Institute for Medical Research, Northwell Health
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/27059652$$D View this record in MEDLINE/PubMed
BookMark	eNqNklFrHCEUhaUkNGmSh_6BIvQlfdhEx1HHl8JmaNrCQkNJnkUdp2s6O07VSZh_X6e7W5rQQkVQ8LuHc4_3FTjofW8BeI3RBUaouFQhXRDBMXoBjgtSsAUtED3Y37HAR-AsxnuUl-CIIfoSHBUcUcFocQxcvbbm--BdnyJsfYDLMflglUnuwcIrWNuui9D1MK0tvLHBDWsbVAevOu8b6Fu4GocxwhuVnJ0lljHavBuoJ3jd-UdYT8lvbArTKThsVRft2e48AXfXH27rT4vVl4-f6-VqYWhZoEVuBWnGDdaCNKXglBpRshZzgbSqFNaGCY2EwJjppqKkMrY1hLD8lDskmpyA91vdYdQb25hsKxuWQ3AbFSbplZNPX3q3lt_8g6S0IBXDWeB8JxD8j9HGJDcumpyD6q0fo8RVDrUkDFX_g5aMMUJ4Rt8-Q-_9GPqcxEyRijNOZ-rNn-Z_u95_WAYut4AJPsZgW2lcyuH7uRfXSYzkPBUyT4X8NRW54t2zir3o39id-qPr7PRvUC6_3m4rfgKw6sUy
CitedBy_id	crossref_primary_10_1002_art_41466 crossref_primary_10_1111_imr_13070 crossref_primary_10_3390_cells10051190 crossref_primary_10_1016_j_coi_2017_06_004 crossref_primary_10_1111_imr_12820 crossref_primary_10_1177_0961203319860191 crossref_primary_10_1016_j_jaut_2017_12_001 crossref_primary_10_3390_pathogens13020136 crossref_primary_10_1111_imr_12660 crossref_primary_10_1093_rheumatology_kew427 crossref_primary_10_1016_j_clim_2016_10_018 crossref_primary_10_1002_art_41675 crossref_primary_10_4049_jimmunol_2300108 crossref_primary_10_1016_j_jaci_2018_10_041 crossref_primary_10_1515_hsz_2020_0377 crossref_primary_10_1016_j_jaut_2017_08_006 crossref_primary_10_1093_ejendo_lvad107 crossref_primary_10_1177_09612033241298729 crossref_primary_10_3389_fimmu_2023_1259827 crossref_primary_10_1136_rmdopen_2023_003800 crossref_primary_10_1016_j_isci_2021_103626 crossref_primary_10_1111_imr_12810 crossref_primary_10_1016_j_jaut_2024_103330 crossref_primary_10_1172_JCI149095 crossref_primary_10_4162_nrp_2017_11_1_57 crossref_primary_10_1016_j_kint_2022_02_041 crossref_primary_10_3389_fimmu_2022_919854 crossref_primary_10_1016_j_autrev_2025_103837 crossref_primary_10_3390_cells8020140 crossref_primary_10_1136_ard_2023_224453 crossref_primary_10_1007_s00125_018_4730_z crossref_primary_10_1002_eji_201848065 crossref_primary_10_1038_nri_2017_19 crossref_primary_10_1007_s12016_017_8608_5 crossref_primary_10_1016_j_imlet_2023_06_005 crossref_primary_10_3389_fphar_2023_1080730 crossref_primary_10_1136_ard_2023_224779 crossref_primary_10_1155_2020_9518137 crossref_primary_10_3390_cells11213391 crossref_primary_10_1016_j_coi_2016_09_003 crossref_primary_10_3389_fimmu_2022_953439 crossref_primary_10_1002_art_42388 crossref_primary_10_3389_fimmu_2021_681105 crossref_primary_10_3389_fimmu_2022_849050 crossref_primary_10_3389_fimmu_2018_00427 crossref_primary_10_3389_fimmu_2019_01694 crossref_primary_10_1080_03009742_2016_1264628 crossref_primary_10_1016_j_autrev_2025_103851 crossref_primary_10_1016_j_coi_2016_07_002 crossref_primary_10_1111_cei_13041 crossref_primary_10_1002_eji_202250319 crossref_primary_10_3390_microorganisms12010230
Cites_doi	10.4049/jimmunol.175.7.4309 10.2337/db13-1798 10.1002/art.27189 10.1073/pnas.1511270112 10.1073/pnas.0803644105 10.1182/blood-2009-09-243071 10.1172/JCI26385 10.1016/S1074-7613(04)00079-2 10.1021/bp060092h 10.4049/jimmunol.173.5.3524 10.1016/j.it.2011.06.004 10.1182/blood-2011-04-345579 10.1155/2014/315179 10.1073/pnas.94.5.1955 10.4049/jimmunol.1001946 10.1002/art.23498 10.1016/j.ajhg.2011.09.002 10.1038/ni.3175 10.1371/journal.pone.0005776 10.4049/jimmunol.167.4.1886 10.1084/jem.20080611 10.4049/jimmunol.1500753 10.1084/jem.20042251 10.4049/jimmunol.1002176 10.1182/blood-2004-01-0346 10.1084/jem.20052033 10.1084/jem.20132203 10.1126/science.1086907 10.1016/j.jim.2007.09.017 10.1182/blood-2010-03-275859 10.1016/j.immuni.2007.01.009 10.1196/annals.1358.019 10.1084/jem.190.11.1697 10.1056/NEJMoa021933 10.1084/jem.20091087 10.1016/j.immuni.2006.10.017 10.4049/jimmunol.180.2.1276 10.1002/art.1780350606 10.1186/ar3042
ContentType	Journal Article
Copyright	2016, American College of Rheumatology 2016, American College of Rheumatology.
Copyright_xml	– notice: 2016, American College of Rheumatology – notice: 2016, American College of Rheumatology.
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QL 7QP 7T5 7TM 7U7 C1K H94 K9. 7U8 7X8 JXQ 5PM
DOI	10.1002/art.39710
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Immunology Abstracts Nucleic Acids Abstracts Toxicology Abstracts Environmental Sciences and Pollution Management AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) TOXLINE MEDLINE - Academic Toxline PubMed Central (Full Participant titles)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Toxicology Abstracts Bacteriology Abstracts (Microbiology B) Nucleic Acids Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Immunology Abstracts Calcium & Calcified Tissue Abstracts Environmental Sciences and Pollution Management TOXLINE MEDLINE - Academic
DatabaseTitleList	MEDLINE Toxicology Abstracts TOXLINE AIDS and Cancer Research Abstracts
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Medicine
EISSN	2326-5205
EndPage	2220
ExternalDocumentID	PMC5523861 4158049501 27059652 10_1002_art_39710 ART39710
Genre	article Journal Article Research Support, N.I.H., Extramural
GrantInformation_xml	– fundername: NIH funderid: R01‐AR‐057084 – fundername: NIAMS NIH HHS grantid: R01 AR057084 – fundername: NIAID NIH HHS grantid: P01 AI073693
GroupedDBID	0R~ 1OC 33P 3SF 4.4 52O 52U 52V 53G 5VS AAESR AAEVG AAFWJ AAHQN AAIPD AAMMB AAMNL AANHP AANLZ AAQQT AASGY AAWTL AAXRX AAYCA AAZKR ABCUV ABJNI ABLJU ABPVW ABQWH ABXGK ACAHQ ACBWZ ACCZN ACFBH ACGFS ACGOF ACIWK ACMXC ACPOU ACPRK ACRPL ACXBN ACXQS ACYXJ ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADNMO ADOZA ADXAS ADZMN AEFGJ AEIGN AEIMD AENEX AEUYR AEYWJ AFBPY AFFPM AFGKR AFRAH AFWVQ AFZJQ AGHNM AGQPQ AGXDD AGYGG AHBTC AHMBA AIACR AIDQK AIDYY AITYG AIURR ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN ALVPJ AMBMR AMYDB ATUGU AZFZN AZVAB BDRZF BFHJK BHBCM BMXJE BROTX BRXPI BY8 C45 DCZOG DIK DRFUL DRMAN DRSTM EBS EJD EMOBN EX3 F00 FUBAC G-S G.N GODZA HGLYW KBYEO LATKE LEEKS LH4 LITHE LOXES LUTES LW6 LYRES MEWTI MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM NF~ O66 O9- OVD P2W PQQKQ QB0 ROL SUPJJ TEORI V9Y WBKPD WHWMO WIH WIJ WIK WOHZO WVDHM WXSBR AAYXX CITATION AAHHS ACCFJ ADZOD AEEZP AEQDE AIWBW AJBDE CGR CUY CVF ECM EIF NPM YCJ 7QL 7QP 7T5 7TM 7U7 C1K H94 K9. 7U8 7X8 JXQ 5PM
ID	FETCH-LOGICAL-c5420-3970b67c1b93d49755c946f1790ba8a1bc69b099116bd8538cefc3368a10003b3
IEDL.DBID	DRFUL
ISICitedReferencesCount	56
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000383498800020&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	2326-5191
IngestDate	Tue Nov 04 01:54:40 EST 2025 Thu Jul 10 19:07:40 EDT 2025 Wed Oct 01 13:01:43 EDT 2025 Sat Nov 29 14:34:22 EST 2025 Thu Apr 03 07:02:56 EDT 2025 Thu Oct 16 04:34:40 EDT 2025 Tue Nov 18 20:59:27 EST 2025 Sun Sep 21 06:17:31 EDT 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	9
Language	English
License	http://onlinelibrary.wiley.com/termsAndConditions#vor 2016, American College of Rheumatology.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c5420-3970b67c1b93d49755c946f1790ba8a1bc69b099116bd8538cefc3368a10003b3
Notes	Drs. Malkiel and Jeganathan, Ms Wolfson, and Drs. Manjarrez Orduño and Marasco contributed equally to this work. Supported by NIH grant R01‐AR‐057084. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Drs. Malkiel and Jeganathan, Ms Wolfson, and Drs. Manjarrez Orduno and Marasco contributed equally to this work.
OpenAccessLink	https://www.ncbi.nlm.nih.gov/pmc/articles/5523861
PMID	27059652
PQID	1813876757
PQPubID	946334
PageCount	11
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_5523861 proquest_miscellaneous_1819143608 proquest_miscellaneous_1814666337 proquest_journals_1813876757 pubmed_primary_27059652 crossref_citationtrail_10_1002_art_39710 crossref_primary_10_1002_art_39710 wiley_primary_10_1002_art_39710_ART39710
PublicationCentury	2000
PublicationDate	September 2016
PublicationDateYYYYMMDD	2016-09-01
PublicationDate_xml	– month: 09 year: 2016 text: September 2016
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States – name: Atlanta
PublicationTitle	Arthritis & rheumatology (Hoboken, N.J.)
PublicationTitleAlternate	Arthritis Rheumatol
PublicationYear	2016
Publisher	Wiley Subscription Services, Inc
Publisher_xml	– name: Wiley Subscription Services, Inc
References	2010; 12 2004; 20 2001; 167 2004; 104 2015; 16 2011; 118 2005; 175 1999; 190 2008; 329 2008; 58 2010; 185 2011; 32 1992; 35 2008; 105 2014; 2014 2006; 116 2010; 62 2014; 211 2015; 195 2008; 180 2003; 349 1997; 94 2010; 116 2005; 201 2006; 22 2015; 64 2010; 115 2004; 173 2015; 112 2006; 25 2005; 1062 2011; 89 2009; 4 2009; 206 2003; 301 2006; 203 2007; 26 2011; 186 e_1_2_7_6_1 e_1_2_7_5_1 e_1_2_7_4_1 e_1_2_7_3_1 e_1_2_7_9_1 e_1_2_7_8_1 e_1_2_7_7_1 e_1_2_7_19_1 e_1_2_7_18_1 e_1_2_7_17_1 e_1_2_7_16_1 e_1_2_7_40_1 e_1_2_7_2_1 e_1_2_7_15_1 e_1_2_7_14_1 e_1_2_7_13_1 e_1_2_7_12_1 e_1_2_7_11_1 e_1_2_7_10_1 e_1_2_7_26_1 e_1_2_7_27_1 e_1_2_7_28_1 e_1_2_7_29_1 e_1_2_7_30_1 e_1_2_7_25_1 e_1_2_7_31_1 e_1_2_7_24_1 e_1_2_7_32_1 e_1_2_7_23_1 e_1_2_7_33_1 e_1_2_7_22_1 e_1_2_7_34_1 e_1_2_7_21_1 e_1_2_7_35_1 e_1_2_7_20_1 e_1_2_7_36_1 e_1_2_7_37_1 e_1_2_7_38_1 e_1_2_7_39_1 20231422 - Blood. 2010 Jun 17;115(24):5026-36 21963258 - Am J Hum Genet. 2011 Oct 7;89(4):496-506 24733829 - J Exp Med. 2014 May 5;211(5):987-1000 18621685 - Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9727-32 20457872 - Blood. 2010 Aug 19;116(7):1070-8 17996249 - J Immunol Methods. 2008 Jan 1;329(1-2):112-24 16461799 - Ann N Y Acad Sci. 2005 Dec;1062:165-74 12920303 - Science. 2003 Sep 5;301(5638):1374-7 26324941 - Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):E5281-9 16485042 - J Clin Invest. 2006 Mar;116(3):724-34 24868563 - J Immunol Res. 2014;2014:315179 20039404 - Arthritis Rheum. 2010 Jan;62(1):201-10 26006014 - Nat Immunol. 2015 Jul;16(7):755-65 15322217 - J Immunol. 2004 Sep 1;173(5):3524-34 11489967 - J Immunol. 2001 Aug 15;167(4):1886-90 21690558 - Blood. 2011 Aug 25;118(8):2150-8 17306569 - Immunity. 2007 Feb;26(2):205-13 9050886 - Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1955-60 10587360 - J Exp Med. 1999 Dec 6;190(11):1697-710 26355154 - J Immunol. 2015 Oct 15;195(8):3716-24 15084273 - Immunity. 2004 Apr;20(4):441-53 20817867 - J Immunol. 2010 Oct 1;185(7):4128-36 16889373 - Biotechnol Prog. 2006 Jul-Aug;22(4):979-88 1599520 - Arthritis Rheum. 1992 Jun;35(6):630-40 16177071 - J Immunol. 2005 Oct 1;175(7):4309-19 14561795 - N Engl J Med. 2003 Oct 16;349(16):1526-33 19917772 - J Exp Med. 2009 Nov 23;206(12 ):2659-69 19488401 - PLoS One. 2009 Jun 02;4(6):e5776 20525218 - Arthritis Res Ther. 2010;12(3):R108 18178868 - J Immunol. 2008 Jan 15;180(2):1276-84 15738055 - J Exp Med. 2005 Mar 7;201(5):703-11 25524915 - Diabetes. 2015 May;64(5):1703-12 17174121 - Immunity. 2006 Dec;25(6):953-62 21752714 - Trends Immunol. 2011 Aug;32(8):388-94 21398610 - J Immunol. 2011 Apr 15;186(8):4640-8 19103878 - J Exp Med. 2009 Jan 16;206(1):139-51 15191950 - Blood. 2004 Dec 1;104(12):3647-54 18512812 - Arthritis Rheum. 2008 Jun;58(6):1762-73 16446381 - J Exp Med. 2006 Feb 20;203(2):393-400
References_xml	– volume: 2014 start-page: 315179 year: 2014 article-title: Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti‐nuclear antibodies publication-title: J Immunol Res – volume: 105 start-page: 9727 year: 2008 end-page: 32 article-title: Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors publication-title: Proc Natl Acad Sci U S A – volume: 20 start-page: 441 year: 2004 end-page: 53 article-title: Reduced competitiveness of autoantigen‐engaged B cells due to increased dependence on BAFF publication-title: Immunity – volume: 167 start-page: 1886 year: 2001 end-page: 90 article-title: Expansion and activation of a population of autoreactive marginal zone B cells in a model of estrogen‐induced lupus publication-title: J Immunol – volume: 116 start-page: 1070 year: 2010 end-page: 8 article-title: High‐throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B‐cell populations publication-title: Blood – volume: 4 start-page: e5776 year: 2009 article-title: Phenotypic characterization of autoreactive B cells: checkpoints of B cell tolerance in patients with systemic lupus erythematosus publication-title: PLoS One – volume: 173 start-page: 3524 year: 2004 end-page: 34 article-title: Mechanism of action of transmembrane activator and calcium modulator ligand interactor‐Ig in murine systemic lupus erythematosus publication-title: J Immunol – volume: 190 start-page: 1697 year: 1999 end-page: 710 article-title: Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations publication-title: J Exp Med – volume: 116 start-page: 724 year: 2006 end-page: 34 article-title: Similarities and differences between selective and nonselective BAFF blockade in murine SLE publication-title: J Clin Invest – volume: 201 start-page: 703 year: 2005 end-page: 11 article-title: Defective B cell tolerance checkpoints in systemic lupus erythematosus publication-title: J Exp Med – volume: 329 start-page: 112 year: 2008 end-page: 24 article-title: Efficient generation of monoclonal antibodies from single human B cells by single cell RT‐PCR and expression vector cloning [published erratum appears in J Immunol Methods 2008;334:142] publication-title: J Immunol Methods – volume: 26 start-page: 205 year: 2007 end-page: 13 article-title: Autoreactivity in human IgG+ memory B cells publication-title: Immunity – volume: 185 start-page: 4128 year: 2010 end-page: 36 article-title: Regulation of the B cell receptor repertoire and self‐reactivity by BAFF publication-title: J Immunol – volume: 32 start-page: 388 year: 2011 end-page: 94 article-title: BAFF and selection of autoreactive B cells publication-title: Trends Immunol – volume: 301 start-page: 1374 year: 2003 end-page: 7 article-title: Predominant autoantibody production by early human B cell precursors publication-title: Science – volume: 1062 start-page: 165 year: 2005 end-page: 74 article-title: B‐cell tolerance checkpoints in healthy humans and patients with systemic lupus erythematosus publication-title: Ann N Y Acad Sci – volume: 118 start-page: 2150 year: 2011 end-page: 8 article-title: Human memory B cells originate from three distinct germinal center‐dependent and independent maturation pathways publication-title: Blood – volume: 206 start-page: 139 year: 2009 end-page: 51 article-title: Functional anergy in a subpopulation of naive B cells from healthy humans that express autoreactive immunoglobulin receptors publication-title: J Exp Med – volume: 115 start-page: 5026 year: 2010 end-page: 36 article-title: Complement receptor 2/CD21 human naive B cells contain mostly autoreactive unresponsive clones publication-title: Blood – volume: 89 start-page: 496 year: 2011 end-page: 506 article-title: Integrating autoimmune risk loci with gene‐expression data identifies specific pathogenic immune cell subsets publication-title: Am J Hum Genet – volume: 104 start-page: 3647 year: 2004 end-page: 54 article-title: Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire publication-title: Blood – volume: 175 start-page: 4309 year: 2005 end-page: 19 article-title: Colocalization of expansion of the splenic marginal zone population with abnormal B cell activation and autoantibody production in B6 mice with an introgressed New Zealand Black chromosome 13 interval publication-title: J Immunol – volume: 64 start-page: 1703 year: 2015 end-page: 12 article-title: Loss of anergic B cells in prediabetic and new‐onset type 1 diabetic patients publication-title: Diabetes – volume: 211 start-page: 987 year: 2014 end-page: 1000 article-title: Identification of a human splenic marginal zone B cell precursor with NOTCH2‐dependent differentiation properties publication-title: J Exp Med – volume: 35 start-page: 630 year: 1992 end-page: 40 article-title: Derivation of the SLEDAI: a disease activity index for lupus patients publication-title: Arthritis Rheum – volume: 62 start-page: 201 year: 2010 end-page: 10 article-title: Effect of long‐term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double‐blind, placebo‐controlled, dose‐ranging study publication-title: Arthritis Rheum – volume: 94 start-page: 1955 year: 1997 end-page: 60 article-title: Peptide inhibition of glomerular deposition of an anti‐DNA antibody publication-title: Proc Natl Acad Sci U S A – volume: 16 start-page: 755 year: 2015 end-page: 65 article-title: Diversity, cellular origin and autoreactivity of antibody‐secreting cell population expansions in acute systemic lupus erythematosus publication-title: Nat Immunol – volume: 180 start-page: 1276 year: 2008 end-page: 84 article-title: Expanded population of activated antigen‐engaged cells within the naive B cell compartment of patients with systemic lupus erythematosus publication-title: J Immunol – volume: 203 start-page: 393 year: 2006 end-page: 400 article-title: A checkpoint for autoreactivity in human IgM memory B cell development publication-title: J Exp Med – volume: 206 start-page: 2659 year: 2009 end-page: 69 article-title: Molecular footprints of a germinal center derivation of human IgM (IgD )CD27 B cells and the dynamics of memory B cell generation publication-title: J Exp Med – volume: 186 start-page: 4640 year: 2011 end-page: 8 article-title: Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM publication-title: J Immunol – volume: 349 start-page: 1526 year: 2003 end-page: 33 article-title: Development of autoantibodies before the clinical onset of systemic lupus erythematosus publication-title: N Engl J Med – volume: 12 start-page: R108 year: 2010 article-title: Decreased frequency and activated phenotype of blood CD27 IgD IgM B lymphocytes is a permanent abnormality in systemic lupus erythematosus patients publication-title: Arthritis Res Ther – volume: 22 start-page: 979 year: 2006 end-page: 88 article-title: A novel strategy for generation of monoclonal antibodies from single B cells using RT‐PCR technique and in vitro expression publication-title: Biotechnol Prog – volume: 58 start-page: 1762 year: 2008 end-page: 73 article-title: Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95 publication-title: Arthritis Rheum – volume: 112 start-page: E5281 year: 2015 end-page: 9 article-title: Complexity of the human memory B‐cell compartment is determined by the versatility of clonal diversification in germinal centers publication-title: Proc Natl Acad Sci U S A – volume: 25 start-page: 953 year: 2006 end-page: 62 article-title: Identification of anergic B cells within a wild‐type repertoire publication-title: Immunity – volume: 195 start-page: 3716 year: 2015 end-page: 24 article-title: A reassessment of IgM memory subsets in humans publication-title: J Immunol – ident: e_1_2_7_31_1 doi: 10.4049/jimmunol.175.7.4309 – ident: e_1_2_7_17_1 doi: 10.2337/db13-1798 – ident: e_1_2_7_18_1 doi: 10.1002/art.27189 – ident: e_1_2_7_23_1 doi: 10.1073/pnas.1511270112 – ident: e_1_2_7_35_1 doi: 10.1073/pnas.0803644105 – ident: e_1_2_7_12_1 doi: 10.1182/blood-2009-09-243071 – ident: e_1_2_7_19_1 doi: 10.1172/JCI26385 – ident: e_1_2_7_21_1 doi: 10.1016/S1074-7613(04)00079-2 – ident: e_1_2_7_7_1 doi: 10.1021/bp060092h – ident: e_1_2_7_20_1 doi: 10.4049/jimmunol.173.5.3524 – ident: e_1_2_7_13_1 doi: 10.1016/j.it.2011.06.004 – ident: e_1_2_7_26_1 doi: 10.1182/blood-2011-04-345579 – ident: e_1_2_7_3_1 doi: 10.1155/2014/315179 – ident: e_1_2_7_39_1 doi: 10.1073/pnas.94.5.1955 – ident: e_1_2_7_11_1 doi: 10.4049/jimmunol.1001946 – ident: e_1_2_7_37_1 doi: 10.1002/art.23498 – ident: e_1_2_7_14_1 doi: 10.1016/j.ajhg.2011.09.002 – ident: e_1_2_7_38_1 doi: 10.1038/ni.3175 – ident: e_1_2_7_36_1 doi: 10.1371/journal.pone.0005776 – ident: e_1_2_7_30_1 doi: 10.4049/jimmunol.167.4.1886 – ident: e_1_2_7_10_1 doi: 10.1084/jem.20080611 – ident: e_1_2_7_25_1 doi: 10.4049/jimmunol.1500753 – ident: e_1_2_7_5_1 doi: 10.1084/jem.20042251 – ident: e_1_2_7_22_1 doi: 10.4049/jimmunol.1002176 – ident: e_1_2_7_28_1 doi: 10.1182/blood-2004-01-0346 – ident: e_1_2_7_33_1 doi: 10.1084/jem.20052033 – ident: e_1_2_7_40_1 doi: 10.1084/jem.20132203 – ident: e_1_2_7_2_1 doi: 10.1126/science.1086907 – ident: e_1_2_7_6_1 doi: 10.1016/j.jim.2007.09.017 – ident: e_1_2_7_27_1 doi: 10.1182/blood-2010-03-275859 – ident: e_1_2_7_34_1 doi: 10.1016/j.immuni.2007.01.009 – ident: e_1_2_7_4_1 doi: 10.1196/annals.1358.019 – ident: e_1_2_7_32_1 doi: 10.1084/jem.190.11.1697 – ident: e_1_2_7_9_1 doi: 10.1056/NEJMoa021933 – ident: e_1_2_7_24_1 doi: 10.1084/jem.20091087 – ident: e_1_2_7_15_1 doi: 10.1016/j.immuni.2006.10.017 – ident: e_1_2_7_16_1 doi: 10.4049/jimmunol.180.2.1276 – ident: e_1_2_7_8_1 doi: 10.1002/art.1780350606 – ident: e_1_2_7_29_1 doi: 10.1186/ar3042 – reference: 25524915 - Diabetes. 2015 May;64(5):1703-12 – reference: 18512812 - Arthritis Rheum. 2008 Jun;58(6):1762-73 – reference: 16461799 - Ann N Y Acad Sci. 2005 Dec;1062:165-74 – reference: 12920303 - Science. 2003 Sep 5;301(5638):1374-7 – reference: 26006014 - Nat Immunol. 2015 Jul;16(7):755-65 – reference: 20457872 - Blood. 2010 Aug 19;116(7):1070-8 – reference: 26324941 - Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):E5281-9 – reference: 20231422 - Blood. 2010 Jun 17;115(24):5026-36 – reference: 26355154 - J Immunol. 2015 Oct 15;195(8):3716-24 – reference: 10587360 - J Exp Med. 1999 Dec 6;190(11):1697-710 – reference: 19488401 - PLoS One. 2009 Jun 02;4(6):e5776 – reference: 19103878 - J Exp Med. 2009 Jan 16;206(1):139-51 – reference: 15738055 - J Exp Med. 2005 Mar 7;201(5):703-11 – reference: 14561795 - N Engl J Med. 2003 Oct 16;349(16):1526-33 – reference: 21963258 - Am J Hum Genet. 2011 Oct 7;89(4):496-506 – reference: 20039404 - Arthritis Rheum. 2010 Jan;62(1):201-10 – reference: 1599520 - Arthritis Rheum. 1992 Jun;35(6):630-40 – reference: 20817867 - J Immunol. 2010 Oct 1;185(7):4128-36 – reference: 18178868 - J Immunol. 2008 Jan 15;180(2):1276-84 – reference: 20525218 - Arthritis Res Ther. 2010;12(3):R108 – reference: 15322217 - J Immunol. 2004 Sep 1;173(5):3524-34 – reference: 15191950 - Blood. 2004 Dec 1;104(12):3647-54 – reference: 24733829 - J Exp Med. 2014 May 5;211(5):987-1000 – reference: 16889373 - Biotechnol Prog. 2006 Jul-Aug;22(4):979-88 – reference: 21398610 - J Immunol. 2011 Apr 15;186(8):4640-8 – reference: 19917772 - J Exp Med. 2009 Nov 23;206(12 ):2659-69 – reference: 17996249 - J Immunol Methods. 2008 Jan 1;329(1-2):112-24 – reference: 15084273 - Immunity. 2004 Apr;20(4):441-53 – reference: 18621685 - Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9727-32 – reference: 21690558 - Blood. 2011 Aug 25;118(8):2150-8 – reference: 21752714 - Trends Immunol. 2011 Aug;32(8):388-94 – reference: 24868563 - J Immunol Res. 2014;2014:315179 – reference: 11489967 - J Immunol. 2001 Aug 15;167(4):1886-90 – reference: 16446381 - J Exp Med. 2006 Feb 20;203(2):393-400 – reference: 9050886 - Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1955-60 – reference: 16177071 - J Immunol. 2005 Oct 1;175(7):4309-19 – reference: 17306569 - Immunity. 2007 Feb;26(2):205-13 – reference: 17174121 - Immunity. 2006 Dec;25(6):953-62 – reference: 16485042 - J Clin Invest. 2006 Mar;116(3):724-34
SSID	ssj0000970605
Score	2.4398232
Snippet	Objective Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still... Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly... Objective Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still... OBJECTIVEAntinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still...
SourceID	pubmedcentral proquest pubmed crossref wiley
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	2210
SubjectTerms	Adult B-Lymphocytes - immunology Female Flow Cytometry Humans Immune Tolerance Lupus Lupus Erythematosus, Systemic - blood Lymphocyte receptors Male Middle Aged T cell receptors
Title	Checkpoints for Autoreactive B Cells in the Peripheral Blood of Lupus Patients Assessed by Flow Cytometry
URI	https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fart.39710 https://www.ncbi.nlm.nih.gov/pubmed/27059652 https://www.proquest.com/docview/1813876757 https://www.proquest.com/docview/1814666337 https://www.proquest.com/docview/1819143608 https://pubmed.ncbi.nlm.nih.gov/PMC5523861
Volume	68
WOSCitedRecordID	wos000383498800020&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVWIB databaseName: Wiley Online Library Full Collection 2020 customDbUrl: eissn: 2326-5205 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000970605 issn: 2326-5191 databaseCode: DRFUL dateStart: 20140101 isFulltext: true titleUrlDefault: https://onlinelibrary.wiley.com providerName: Wiley-Blackwell
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1La9wwEB6STQi99JG-3KZBDT30YmLZlmzRU7Lt0kMalpLA3oyklYmpay9rb8v--45kr9slSSn0ZtAIrNE30jd6fAJ4xwxNBQsCnyGZxQRFUAwpSX1l6FxzyfPYSPfYRHJ5mc5mYroDHzZ3YTp9iGHBzUaGG69tgEvVnP4WDUXPYsKe2OtVeyHilo1g7-PXyfXFsMQSCCsNw9zzciH3kavQjbZQEJ4O9bdnpFs08_ZpyT9ZrJuGJo_-qwGP4WHPPslZB5cnsGOqQzj40u-vP4VifGP0t0VdVG1DkM6SMytxYKQbFMk5GZuybEhREaSNZIrgdaIEJTm3x99JnZOL1WLVkGkn1tqQbkvZzIlak0lZ_yTjdVt_N-1y_QyuJ5-uxp_9_jEGX7PY3rJGZyqeaKpENI9FwpgWMc-twJeSqaRKc6GQblLK1Rw5QKpNrqOIY5HNu1T0HEZVXZmXQFjKjUbqYCSmQwyrRgbxwQKDuVsulPLg_aZDMt0rldsHM8qs01gOM3Rd5lznwclguujkOe4yOtr0atZHaJMhs4lSq2STePB2KMbYshsmsjL1ytnEmN5F0d9tBHJOHqQevOiAMvwJwpIJzkIPki0IDQZW23u7pCpunMY3Y8ilOEVXOAjd37gM8x738erfTV_DA-R9vDsqdwSjdrkyb2Bf_2iLZnkMu8ksPe6D6ReVzSEM
linkProvider	Wiley-Blackwell
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3fb9MwED5NGwJexo8xFhhg0B72EjVOYieWeNkK1RBdVaFN2lsUu44WEZKqSUH97zk7aaAamybxFslnKTl_53znH98BHDFNY8E8z2VIZjFBERRDKqWu1HSmeMqzUKe22EQ0mcRXV2K6BR_Xd2FafYh-wc1Ehp2vTYCbBenBH9VQdC1m7JG5X7UTIowQ3zufvo0ux_0aiyeMNgyz9eV87iJZoWtxIc8f9P03f0k3eObN45J_01j7Hxo9-b8veAq7Hf8kJy1gnsGWLp_Dw_Nuh30P8uG1Vt_nVV42NUFCS06MyIFO7bRITslQF0VN8pIgcSRThK-VJSjIqTkAT6qMjJfzZU2mrVxrTdpNZT0jckVGRfWLDFdN9UM3i9ULuBx9vhieuV05Blex0NyzRm9KHikqRTALRcSYEiHPjMSXTOOUSsWFRMJJKZczZAGx0pkKAo5NJvOSwT5sl1WpD4CwmGuF5EGnmBAx7BpoRAjzNGZvmZDSgeP1iCSq0yo3JTOKpFVZ9hN0XWJd58CH3nTeCnT8y-hwPaxJF6N1gtwmiI2WTeTA-74Zo8tsmaSlrpbWJsQELwjuthHIOrkXO_CyRUr_Jn5kyhsx34FoA0O9gVH33mwp82ur8s0YsilO0RUWQ7d_XIKZj314dX_Td_Do7OJ8nIy_TL6-hsfIAnl7cO4QtpvFUr-BB-pnk9eLt11M_QYFFCQU
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3fi9QwEB6OPTl8OX_fVU-N4oMv5Zq2SRvw5W7Porgui3hwb6VJU65Y22XbVfa_d5J2q8upCL4VMoFmMpN8k0y-AXjFNI0F8zyXIZjFAEVQdKmMulLTXPGMF6HObLGJaD6Pr67EYg_ebN_C9PwQ44Gb8Qy7XhsH18u8OP3JGoqqxYg9Mu-r9kNTRGYC-xefksvZeMbiCcMNw2x9OZ-7CFbollzI80_H_rtb0g2ceTNd8lcYa_eh5M7_jeAuHA74k5z1BnMP9nR9Hw4-DjfsD6CcXmv1ZdmUddcSBLTkzJAc6Mwui-ScTHVVtaSsCQJHskDztbQEFTk3CfCkKchsvVy3ZNHTtbakv1TWOZEbklTNdzLddM1X3a02D-Eyeft5-s4dyjG4ioXmnTVqU_JIUSmCPBQRY0qEvDAUXzKLMyoVFxIBJ6Vc5ogCYqULFQQcm0zkJYNHMKmbWh8DYTHXCsGDzjAgYtg10GghzNMYvRVCSgdeb2ckVQNXuSmZUaU9y7KfoupSqzoHXo6iy56g43dCJ9tpTQcfbVPENkFsuGwiB16Mzehd5sokq3WztjIhBnhB8HcZgaiTe7EDR72ljH_iR6a8EfMdiHZsaBQw7N67LXV5bVm-GUM0xSmqwtrQnweXYuRjPx7_u-hzOFhcJOns_fzDE7iNIJD3eXMnMOlWa_0UbqlvXdmung0u9QNcjCOP
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Checkpoints+for+Autoreactive+B+Cells+in+the+Peripheral+Blood+of+Lupus+Patients+Assessed+by+Flow+Cytometry&rft.jtitle=Arthritis+%26+rheumatology+%28Hoboken%2C+N.J.%29&rft.au=Malkiel%2C+Susan&rft.au=Jeganathan%2C+Venkatesh&rft.au=Wolfson%2C+Stacey&rft.au=Ordu%C3%B1o%2C+Nataly+Manjarrez&rft.date=2016-09-01&rft.issn=2326-5191&rft.eissn=2326-5205&rft.volume=68&rft.issue=9&rft.spage=2210&rft.epage=2220&rft_id=info:doi/10.1002%2Fart.39710&rft_id=info%3Apmid%2F27059652&rft.externalDocID=PMC5523861
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2326-5191&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2326-5191&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2326-5191&client=summon