title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Pavón
authors.forename: Esther
authors.initials: E
authors.lastname: Zumaquero
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosal-Vela
authors.forename: Keng-Meng
authors.initials: KM
authors.lastname: Khoo
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerezo-Wallis
authors.forename: Sonia
authors.initials: S
authors.lastname: García-Rodríguez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Carrascal
authors.forename: Joaquin
authors.initials: J
authors.lastname: Abian
authors.forename: Richard
authors.initials: R
authors.lastname: Graeff
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Callejas-Rubio
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Mercedes
authors.initials: M
authors.lastname: Zubiaur
authors.forename: Jaime
authors.initials: J
authors.lastname: Sancho
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis / Q000276:immunology*; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D051997:ADP-ribosyl Cyclase 1