RESUMO
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Assuntos
Humanos , Fibromialgia/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Estimulantes do Sistema Nervoso Central/antagonistas & inibidoresRESUMO
In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hpalpha polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2-2, or Hp 2-1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0 625 (Hp(2)), 0.281 (Hp(1S)), and 0.093 (Hp(1F)) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp(2)), 0.233 (Hp(1S)), and 0.033 (Hp1(1F)), which clearly indicated an increased frequency of Hp(2), a similar proportion of Hp(1S) and a diminished proportion of Hp(1F) in SLE patients compared with that in healthy controls. Preferential Hpalpha2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders.
Assuntos
Haptoglobinas/genética , Lúpus Eritematoso Sistêmico/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Eletroforese em Gel Bidimensional , Frequência do Gene , Haptoglobinas/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genéticaRESUMO
In this study we have determined whether there is a relationship between CD38 expression on T cells, its distribution in different membrane microdomains, and T cell activation in SLE patients. The data show that CD38 expression is augmented in ex vivo CD3+, CD4+, CD8+, and CD25+ SLE T cells, which correlates with its increased insolubility in Brij 98 detergent, and its translocation into lipid rafts. Moreover, SLE T cells show an altered CD4:CD8 ratio, which is due to a decreased proportion of CD4+ T cells and a concomitant increase in the proportion of CD8+ T cells. These data are consistent with the increased CD38 expression and lipid raft formation, and the significant reduction in the CD4:CD8 ratio observed in mitogen-stimulated normal T cells as compared with that in ex vivo untouched normal T cells. Increased expression of CD38 in floating rafts from SLE T cells, or from activated normal T cells may modulate TCR signaling by providing or sequestering signaling molecules to the engaged TCR.