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.

Autor: Pavón EJ; Instituto de Parasitología y Biomedicina López-Neyra (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Parque Tecnológico de Ciencias de la Salud (PTS), Avenida del Conocimiento s/n, 18016 Armilla, Spain., Zumaquero E, Rosal-Vela A, Khoo KM, Cerezo-Wallis D, García-Rodríguez S, Carrascal M, Abian J, Graeff R, Callejas-Rubio JL, Ortego-Centeno N, Malavasi F, Zubiaur M, Sancho J
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2013 May; Vol. 62 (2), pp. 232-43. Date of Electronic Publication: 2013 Mar 26.
DOI: 10.1016/j.cyto.2013.02.023
Abstrakt: CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca(2+)-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.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: