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 CHOI, Jin-Young
HO, John Hsi-en
BUNIN, Viviane
KIM, Sang Taek
CRAFT, Joseph 2015
dc.identifier.citation ARTHRITIS & RHEUMATOLOGY, v.67, n.4, p.988-999, 2015
dc.identifier.issn 2326-5191
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 LIM/03 LIM/61 LIM/17 LIM/60
dc.identifier.doi 10.1002/art.39020
dc.identifier.pmid 25581113
dc.type.category original article
dc.type.version publishedVersion PASOTO, Sandra G.:HC:LIM/03 CARRASCO, Solange:FM:MCM BORBA, Eduardo F.:FM:MCM GONCALVES, Celio R.:HC:ICHC COSTA, Priscila R.:HC:LIM/61 KALLAS, Esper G.:FM:MCM BONFA, Eloisa:FM:MCM · 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 2-s2.0-84925762443 WOS:000351841800018 HOBOKEN USA
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dc.description.index MEDLINE
dc.identifier.eissn 2326-5205
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hcfmusp.citation.wos 97 Brasil Estados Unidos
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