Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCHOI, Jin-Young
dc.contributor.authorHO, John Hsi-en
dc.contributor.authorPASOTO, Sandra G.
dc.contributor.authorBUNIN, Viviane
dc.contributor.authorKIM, Sang Taek
dc.contributor.authorCARRASCO, Solange
dc.contributor.authorBORBA, Eduardo F.
dc.contributor.authorGONCALVES, Celio R.
dc.contributor.authorCOSTA, Priscila R.
dc.contributor.authorKALLAS, Esper G.
dc.contributor.authorBONFA, Eloisa
dc.contributor.authorCRAFT, Joseph
dc.date.accessioned2015-08-14T15:34:37Z
dc.date.available2015-08-14T15:34:37Z
dc.date.issued2015
dc.description.abstractObjective. To assess circulating follicular helper T (Tfh)-like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods. Blood samples from patients with SLE, as well as blood samples from patients with Behcet's disease (BD) and healthy individuals as controls, were analyzed. In all samples, circulating Tfh-like cells were enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T cell costimulator (ICOS), and programmed death 1 (PD-1) protein, as well as secretion of interleukin-21 (IL-21). The frequency of circulating Tfh-like cells was compared to that of circulating plasmablasts (CD19+IgD-CD38+). In addition, the possible association of circulating Tfh-like cells with the SLE Disease Activity Index (SLEDAI) was evaluated. Results. The subset of circulating Tfh-like T cells, identified as CXCR5(high)ICOS(high)PD-1(high), was expanded in the blood of SLE patients compared to controls. Circulating Tfh-like cells were found to produce IL-21 and had lower expression of CCR7 as compared to that in circulating CXCR5(high) central memory T cells, thereby enabling their distinction. Expression of PD-1, but not ICOS or CXCR5, was significantly elevated in circulating Tfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5(high) circulating Tfh-like cells correlated with the SLEDAI, frequency of circulating plasmablasts, and anti-double-stranded DNA antibody positivity, but not with disease duration or past organ injury; rather, this cell profile appeared to be a reflection of current active disease. Conclusion. Circulating Tfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T cell-B cell collaboration, with a causal relationship that is central to disease pathogenesis. These findings also suggest that circulating Tfh-like cells provide a surrogate for aberrant germinal center activity in SLE, and that their PD-1 expression offers a tool for measuring disease activity and monitoring the response to therapies.
dc.description.indexMEDLINE
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP) [2011/02119-0]
dc.description.sponsorshipAbbVie
dc.description.sponsorshipAlliance for Lupus Research
dc.description.sponsorshipNIH [AR-040072, AR-053495, T32-AR-07107]
dc.description.sponsorshipRheumatology Research Foundation (Scientist Development Award)
dc.description.sponsorshipBiogen Idec
dc.description.sponsorshipSanofi
dc.description.sponsorshipNovo Nordisk
dc.description.sponsorshipPfizer
dc.description.sponsorshipModerna
dc.identifier.citationARTHRITIS & RHEUMATOLOGY, v.67, n.4, p.988-999, 2015
dc.identifier.doi10.1002/art.39020
dc.identifier.eissn2326-5205
dc.identifier.issn2326-5191
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/9674
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.relation.ispartofArthritis & Rheumatology
dc.rightsrestrictedAccess
dc.rights.holderCopyright WILEY-BLACKWELL
dc.subject.othercxc chemokine receptor-5
dc.subject.otherb-cells
dc.subject.othergerminal-centers
dc.subject.otherdisease-activity
dc.subject.otherplasma-cells
dc.subject.othertranscription factor
dc.subject.otherantibody-responses
dc.subject.othereffector-memory
dc.subject.otheri interferons
dc.subject.otherautoimmunity
dc.subject.wosRheumatology
dc.titleCirculating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalCHOI, Jin-Young:Yale Univ, Sch Med, New Haven, CT USA
hcfmusp.author.externalHO, John Hsi-en:Yale Univ, Sch Med, New Haven, CT USA
hcfmusp.author.externalBUNIN, Viviane:Yale Univ, Sch Med, New Haven, CT USA
hcfmusp.author.externalKIM, Sang Taek:Yale Univ, Sch Med, New Haven, CT USA
hcfmusp.author.externalCRAFT, Joseph:Yale Univ, Sch Med, New Haven, CT USA
hcfmusp.citation.scopus240
hcfmusp.contributor.author-fmusphcSANDRA GOFINET PASOTO
hcfmusp.contributor.author-fmusphcSOLANGE CARRASCO
hcfmusp.contributor.author-fmusphcEDUARDO FERREIRA BORBA NETO
hcfmusp.contributor.author-fmusphcCELIO ROBERTO GONCALVES
hcfmusp.contributor.author-fmusphcPRISCILA BERENICE DA COSTA
hcfmusp.contributor.author-fmusphcESPER GEORGES KALLAS
hcfmusp.contributor.author-fmusphcELOISA SILVA DUTRA DE OLIVEIRA BONFA
hcfmusp.description.beginpage988
hcfmusp.description.endpage999
hcfmusp.description.issue4
hcfmusp.description.volume67
hcfmusp.origemWOS
hcfmusp.origem.pubmed25581113
hcfmusp.origem.scopus2-s2.0-84925762443
hcfmusp.origem.wosWOS:000351841800018
hcfmusp.publisher.cityHOBOKEN
hcfmusp.publisher.countryUSA
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