Repositório Científico do Instituto Nacional de Saúde >
Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis >
DPSPDNT - Artigos em revistas internacionais >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/265

Title: Low frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated with CTLA4 and TGFbeta gene variants
Authors: Barreto, M.
Ferreira, R.C.
Lourenço, L.
Moraes-Fontes, M.F.
Santos, E.
Alves, M.
Carvalho, C.
Martins, B.
Andreia, R.
Viana, J.F.
Vasconcelos, C.
Mota-Vieira, L.
Ferreira, C.
Demengeot, J.
Vicente, A.M.
Keywords: Determinantes Imunológicos em Doenças Crónicas
Issue Date: 27-Jan-2009
Publisher: BioMed Central
Citation: BMC Immunol. 2009 Jan 27;10:5
Abstract: 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.
Peer Reviewed: yes
URI: http://hdl.handle.net/10400.18/265
ISSN: 1471-2172
Publisher version: http://www.biomedcentral.com/1471-2172/10/5
Appears in Collections:DPSPDNT - Artigos em revistas internacionais

Files in This Item:

File Description SizeFormat
Low frequency of CD4+CD25+ Treg in SLE patients a heritable trait associated with CTLA4 and TGFbeta gene variants.pdf649.36 kBAdobe PDFView/Open
Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

  © 2010 www.insa.pt - Todos os direitos reservados | Feedback Ministério da Saúde

Estamos no RCAAP Governo Português separator Ministério da Educação e Ciência   Fundação para a Ciência e a Tecnologia

Financiado por:

POS_C UE