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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, Constantin
dc.contributor.authorBarreto, Marta
dc.contributor.authorFerreira, Ricardo C.
dc.contributor.authorCosta, Nuno
dc.contributor.authorVenda, Lara L.
dc.contributor.authorPereira, Clara
dc.contributor.authorCarvalho, Claudia
dc.contributor.authorMorães-Fontes, Maria Francisca
dc.contributor.authorFerreira, Carlos M.
dc.contributor.authorVasconcelos, Carlos
dc.contributor.authorViana, João F.
dc.contributor.authorSantos, Eugenia
dc.contributor.authorMartins, Berta
dc.contributor.authorDemengeot, Jocelyne
dc.contributor.authorVicente, Astrid M.
dc.date.accessioned2016-06-09T16:14:16Z
dc.date.available2016-06-09T16:14:16Z
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.pt_PT
dc.description.sponsorshipFundação para a Ciência e a Tecnologia grant: (POCTI/SAU-MMO/59913/2004), and FCT postdoctoral fellowships.pt_PT
dc.identifier.citationFesel C, Barreto M, Ferreira RC, Costa N, Venda LL, et al. (2012) Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL- 2/CD25-Mediated Effects Suggested by Coreferentiality Modeling. PLoS ONE 7(3): e33992. doi:10.1371/journal.pone.0033992pt_PT
dc.identifier.doi10.1371/journal.pone.0033992pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/638
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033992pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAdolescentpt_PT
dc.subjectAdultpt_PT
dc.subjectAgedpt_PT
dc.subjectAutoantibodiespt_PT
dc.subjectCD4 Lymphocyte Countpt_PT
dc.subjectFamilypt_PT
dc.subjectFemalept_PT
dc.subjectGenotypept_PT
dc.subjectHumanspt_PT
dc.subjectImmunoglobulin Gpt_PT
dc.subjectInterleukin-2pt_PT
dc.subjectInterleukin-2 Receptor alpha Subunitpt_PT
dc.subjectLupus Erythematosus, Systemicpt_PT
dc.subjectMalept_PT
dc.subjectMiddle Agedpt_PT
dc.subjectPhenotypept_PT
dc.subjectProtein Bindingpt_PT
dc.subjectT-Lymphocytespt_PT
dc.subjectT-Lymphocytes, Regulatorypt_PT
dc.subjectYoung Adultpt_PT
dc.subjectModels, Immunologicalpt_PT
dc.titleCompensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modelingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage17pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLoS ONEpt_PT
oaire.citation.volume7pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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