Método para el diagnóstico, pronóstico y/o tratamiento del lupus eritematoso sistémico

[EN] The present invention relates to the field of biomedicine. Specifically, the invention provides methods that allow the diagnosis, prognosis and/or treatment of systemic lupus erythematosus (SLE) disease..[ES] La presente invención se encuadra dentro del campo de la biomedicina. Especificamente, provee de métodos que permiten el diagnóstico, el pronóstico y/o el tratamiento de la enfermedad del Lupus Eritematoso Sistémico (LES).Peer reviewedConsejo Superior de Investigaciones Científicas (España), Tan Tock Seng HospitalA1 Solicitud de patente con informe sobre el estado de la técnic

THE CD38 PARADIGM : A STUDY OF ITS DISTRIBUTION AND ROLE IN THE NON-HEMATOPOIETIC SYSTEM

Ph.DDOCTOR OF PHILOSOPH

Increased CD38 expression in T cells and circulating anti-CD38 IgG autoantibodies differentially correlate with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients

CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca2+-mobilizing second messengers. In mammals, CD38 also functions as a receptor. In this study CD38 expression in CD4+, CD8+, or CD25+ T cells was significantly higher in systemic lupus erythematosus (SLE) patients than in Normal controls. Increased CD38 expression in SLE T cells correlated with plasma levels of Th2 (IL-4, IL-10, IL-13) and Th1 (IL-1β, IL-12, IFN-γ, TNF-α) cytokines, and was more prevalent in clinically active SLE patients than in Normal controls. In contrast, elevated anti-CD38 IgG autoantibodies were more frequent in clinically quiescent SLE patients (SLEDAI=0) than in Normal controls, and correlated with moderate increased plasma levels of IL-10 and IFN-γ. However, clinically active SLE patients were mainly discriminated from quiescent SLE patients by increased levels of IL-10 and anti-dsDNA antibodies, with odds ratios (ORs) of 3.7 and 4.8, respectively. Increased frequency of anti-CD38 autoantibodies showed an inverse relationship with clinical activity (OR=0.43), and in particular with the frequency of anti-dsDNA autoantibodies (OR=0.21). Increased cell death occurred in CD38+ Jurkat T cells treated with anti-CD38+ SLE plasmas, and not in these cells treated with anti-CD38- SLE plasmas, or Normal plasmas. This effect did not occur in CD38-negative Jurkat T cells, suggesting that it could be attributed to anti-CD38 autoantibodies. These results support the hypothesis that anti-CD38 IgG autoantibodies or their associated plasma factors may dampen immune activation by affecting the viability of CD38+ effector T cells and may provide protection from certain clinical SLE features. © 2013 Elsevier Ltd.Peer Reviewe

Localization of the cyclic ADP-ribose-dependent calcium signaling pathway in hepatocyte nucleus

10.1074/jbc.M908231199Journal of Biological Chemistry2753224807-24817JBCH