Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author CHOI, Jin-Young
HO, John Hsi-en
PASOTO, Sandra G. FMUSP-HC
BUNIN, Viviane
KIM, Sang Taek
CARRASCO, Solange FMUSP-HC
BORBA, Eduardo F. FMUSP-HC
GONCALVES, Celio R. FMUSP-HC
COSTA, Priscila R. FMUSP-HC
KALLAS, Esper G. FMUSP-HC
BONFA, Eloisa FMUSP-HC
CRAFT, Joseph
dc.date.issued 2015
dc.identifier.citation ARTHRITIS & RHEUMATOLOGY, v.67, n.4, p.988-999, 2015
dc.identifier.issn 2326-5191
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/9674
dc.description.abstract Objective. 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.sponsorship · Sao Paulo Research Foundation (FAPESP) [2011/02119-0]
· AbbVie
· Alliance for Lupus Research
· NIH [AR-040072, AR-053495, T32-AR-07107]
· Rheumatology Research Foundation (Scientist Development Award)
· Biogen Idec
· Sanofi
· Novo Nordisk
· Pfizer
· Moderna
dc.language.iso eng
dc.publisher WILEY-BLACKWELL
dc.relation.ispartof Arthritis & Rheumatology
dc.rights restrictedAccess
dc.subject.other cxc chemokine receptor-5; b-cells; germinal-centers; disease-activity; plasma-cells; transcription factor; antibody-responses; effector-memory; i interferons; autoimmunity
dc.title Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus
dc.type article
dc.rights.holder Copyright WILEY-BLACKWELL
dc.description.group LIM/03
dc.description.group LIM/61
dc.description.group LIM/17
dc.description.group LIM/60
dc.identifier.doi 10.1002/art.39020
dc.identifier.pmid 25581113
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author PASOTO, Sandra G.:HC:LIM/03
hcfmusp.author CARRASCO, Solange:FM:MCM
hcfmusp.author BORBA, Eduardo F.:FM:MCM
hcfmusp.author GONCALVES, Celio R.:HC:ICHC
hcfmusp.author COSTA, Priscila R.:HC:LIM/61
hcfmusp.author KALLAS, Esper G.:FM:MCM
hcfmusp.author BONFA, Eloisa:FM:MCM
hcfmusp.author.external · CHOI, Jin-Young:Yale Univ, Sch Med, New Haven, CT USA
· HO, John Hsi-en:Yale Univ, Sch Med, New Haven, CT USA
· BUNIN, Viviane:Yale Univ, Sch Med, New Haven, CT USA
· KIM, Sang Taek:Yale Univ, Sch Med, New Haven, CT USA
· CRAFT, Joseph:Yale Univ, Sch Med, New Haven, CT USA
hcfmusp.origem.id 2-s2.0-84925762443
hcfmusp.origem.id WOS:000351841800018
hcfmusp.publisher.city HOBOKEN
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
dc.identifier.eissn 2326-5205
hcfmusp.citation.scopus 98
hcfmusp.citation.wos 97
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Estados Unidos
hcfmusp.citation.toppaper Highly


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