Mostrando recursos 1 - 7 de 7

  1. Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

    Martins, M; Williams, A H; Comeau, M; Marion, M; Ziegler, J T; Freedman, B I; Merrill, J T; Glenn, S B; Kelly, J A; Sivils, K M; James, J A; Guthridge, J M; Alarcón-Riquelme, M E; Bae, S-C; Kim, J-H; Kim, D; Anaya, J-M; Boackle, S A; Criswell, L A; Kimberly, R P; Alarcón, G S; Brown, E E; Vilá, L M; Petri, M A; Ramsey-Goldman, R; Niewold, T B; Tsao, B P; Gilkeson, G S; Kamen, D L; Jacob, C O; Stevens, A M; Gaffney, P M; Harley, J B; Langefeld, C D; Fesel, C
    A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) <...

  2. A3.6 Two components contributing to reduced treg surface CD25 in sle patients and their unaffected relatives

    Costa, N; Marques, O; Godinho, S; Carvalho, C; Leal, B; Vasconcelos, C; Marinho, A; Moraes-Fontes, M F; Gomes da Costa, A; Ponte, C; Marques, R; Coias, T; Martins, A R; Viana, J F; Martins, B; Fesel, C
    Background FOXP3+ regulatory T-cells (Tregs) in Systemic Lupus Erythematosus (SLE) are in a functionally deficient state with a characteristic reduction or absence of surface CD25 (the IL-2 receptor alpha chain). Genetic variation in the CD25-encoding IL2RA locus is associated with other autoimmune disorders.

  3. Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

    Costa, Nuno; Pires, Ana E.; Gabriel, Ana M.; Goulart, Luiz F.; Pereira, Clara; Leal, Bárbara; Queiros, Ana C.; Chaara, Wahiba; Moraes-Fontes, Maria F.; Vasconcelos, Carlos; Ferreira, Carlos; Martins, Jorge; Bastos, Marina; Santos, Maria J.; Pereira, Maria A.; Martins, Berta; Lima, Margarida; João, Cristina; Six, Adrien; Demengeot, Jocelyne; Fesel, Constantin
    Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.

  4. Coreferentiality: A New Method for the Hypothesis-Based Analysis of Phenotypes Characterized by Multivariate Data

    Fesel, Constantin
    Many multifactorial biologic effects, particularly in the context of complex human diseases, are still poorly understood. At the same time, the systematic acquisition of multivariate data has become increasingly easy. The use of such data to analyze and model complex phenotypes, however, remains a challenge. Here, a new analytic approach is described, termed coreferentiality, together with an appropriate statistical test. Coreferentiality is the indirect relation of two variables of functional interest in respect to whether they parallel each other in their respective relatedness to multivariate reference data, which can be informative for a complex effect or phenotype. It is shown...

  5. Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

    Dalko, Esther; Das, Bidyut; Herbert, Fabien; Fesel, Constantin; Pathak, Sulabha; Tripathy, Rina; Cazenave, Pierre-André; Ravindran, Balachandran; Sharma, Shobhona; Pied, Sylviane
    Several immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria,...

  6. Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

    Costa, Nuno; Pires, Ana E; Gabriel, Ana M; Goulart, Luiz F; Pereira, Clara; Leal, Barbara; Queiros, Ana C; Chaara, Wahiba; Moraes-Fontes, Maria F; Vasconcelos, Carlos; Ferreira, Carlos; Martins, Jorge; Bastos, Marina; Santos, Maria J; Pereira, Maria A; Martins, Berta; Lima, Margarida; João, Cristina; Six, Adrien; Demengeot, Jocelyne; Fesel, Constantin

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

    Fesel, Constantin; Barreto, Marta; Ferreira, Ricardo C.; Costa, Nuno; Venda, Lara L.; Pereira, Clara; Carvalho, Claudia; Morães-Fontes, Maria Francisca; Ferreira, Carlos M.; Vasconcelos, Carlos; Viana, João F.; Santos, Eugenia; Martins, Berta; Demengeot, Jocelyne; Vicente, Astrid M.
    In 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...

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