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Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling

2012-03-29Journal article Open access
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dc.contributor.authorFesel, C.
dc.contributor.authorBarreto, M.
dc.contributor.authorFerreira, R.C.
dc.contributor.authorCosta, N.
dc.contributor.authorVenda, L.L.
dc.contributor.authorPereira, C.
dc.contributor.authorCarvalho, C.
dc.contributor.authorMorães-Fontes, M.F.
dc.contributor.authorFerreira, C.M.
dc.contributor.authorVasconcelos, C.
dc.contributor.authorViana, J.F.
dc.contributor.authorSantos, E.
dc.contributor.authorMartins, B.
dc.contributor.authorDemengeot, J.
dc.contributor.authorVicente, A.M.
dc.date.accessioned2012-05-31T14:45:42Z
dc.date.available2012-05-31T14:45:42Z
dc.date.issued2012-03-29
dc.description.abstractIn human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.por
dc.identifier.citationPLoS One. 2012;7(3):e33992. Epub 2012 Mar 29por
dc.identifier.issnESSN: 1932-6203
dc.identifier.otherdoi: 10.1371/journal.pone.0033992
dc.identifier.urihttp://hdl.handle.net/10400.18/871
dc.language.isoengpor
dc.publisherPublic Library of Sciencepor
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033992por
dc.subjectDeterminantes Imunológicos em Doenças Crónicaspor
dc.titleCompensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modelingpor
dc.typejournal article
dspace.entity.typePublication
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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