Repository logo
 
Publication

Low frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated with CTLA4 and TGFbeta gene variants.

2009-01-27Journal article Open access
Simple item page
dc.contributor.authorBarreto, M.
dc.contributor.authorFerreira, R.
dc.contributor.authorLourenço, L.
dc.contributor.authorMoraes-Fontes, M.
dc.contributor.authorSantos, E.
dc.contributor.authorAlves, M.
dc.contributor.authorCarvalho, C.
dc.contributor.authorMartins, B.
dc.contributor.authorAndreia, R.
dc.contributor.authorViana, J.
dc.contributor.authorVasconcelos, C.
dc.contributor.authorMota-Vieira, L.
dc.contributor.authorFerreira, C.
dc.contributor.authorDemengeot, J.
dc.contributor.authorVicente, A.
dc.date.accessioned2012-02-28T13:32:51Z
dc.date.available2012-02-28T13:32:51Z
dc.date.issued2009-01-27
dc.description.abstractAbstract BACKGROUND: CD4+CD25+ regulatory T cells play an essential role in maintaining immune homeostasis and preventing autoimmunity. Therefore, defects in Treg development, maintenance or function have been associated with several human autoimmune diseases including Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease characterized by loss of tolerance to nuclear components and significantly more frequent in females. RESULTS: To investigate the involvement of Treg in SLE pathogenesis, we determined the frequency of CD4+CD25+CD45RO+ T cells, which encompass the majority of Treg activity, in the PBMC of 148 SLE patients (76 patients were part of 54 families), 166 relatives and 117 controls. SLE patients and their relatives were recruited in several Portuguese hospitals and through the Portuguese Lupus Association. Control individuals were blood donors recruited from several regional blood donor centers. Treg frequency was significantly lower in SLE patients than healthy controls (z = -6.161, P < 0.00001) and intermediate in the relatives' group. Remarkably, this T cell subset was also lower in females, most strikingly in the control population (z = 4.121, P < 0.001). We further ascertained that the decreased frequency of Treg in SLE patients resulted from the specific reduction of bona fide FOXP3+CD4+CD25+ Treg. Treg frequency was negatively correlated with SLE activity index (SLEDAI) and titers of serum anti-dsDNA antibodies. Both Treg frequency and disease activity were modulated by IVIg treatment in a documented SLE case. The segregation of Treg frequency within the SLE families was indicative of a genetic trait. Candidate gene analysis revealed that specific variants of CTLA4 and TGFbeta were associated with the decreased frequency of Treg in PBMC, while FOXP3 gene variants were associated with affection status, but not with Treg frequency. CONCLUSION: SLE patients have impaired Treg production or maintenance, a trait strongly associated with SLE disease activity and autoantibody titers, and possibly resulting from the inability to convert FOXP3+CD25- into FOXP3+CD25+ T cells. Treg frequency is highly heritable within SLE families, with specific variants of the CTLA4 and TGFbeta genes contributing to this trait, while FOXP3 contributes to SLE through mechanisms not involving a modulation of Treg frequency. These findings establish that the genetic components in SLE pathogenesis include genes related to Treg generation or maintenance.por
dc.identifier.citationBMC Immunol. 2009 Jan 27;10:5.por
dc.identifier.issn1471-2172
dc.identifier.urihttp://hdl.handle.net/10400.16/897
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherBioMed Centralpor
dc.relation.publisherversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656467/pdf/1471-2172-10-5.pdfpor
dc.titleLow frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated with CTLA4 and TGFbeta gene variants.por
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceLondonpor
oaire.citation.titleBMC immunologypor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Low frequency of CD4+CD25+ Treg in SLE patients.pdf
Size:
502.43 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

UIC - Artigos publicados em revistas indexadas na Medline
SIM - Artigos publicados em revistas indexadas na Medline