The soluble CD40 ligand sCD154 in systemic lupus erythematosus
Kazunori Kato, … , Hiroshi Hashimoto, Thomas J. Kipps
Kazunori Kato, … , Hiroshi Hashimoto, Thomas J. Kipps
Published October 1, 1999
Citation Information: J Clin Invest. 1999;104(7):947-955. https://doi.org/10.1172/JCI7014.
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Article

The soluble CD40 ligand sCD154 in systemic lupus erythematosus

Abstract

We found that the plasma of patients with active systemic lupus erythematosus (SLE) could induce a human B-cell line (Ramos) to express high levels of immune accessory molecules that are commonly found on blood B cells of patients with active SLE. The ability of SLE plasma to induce such phenotypic changes could be abrogated by neutralizing antibodies specific for the CD40 ligand (CD154) but not by antibodies to TNF-α. Immunoprecipitation studies with anti-CD154 identified a 20-kDa protein in the plasma of SLE patients with active disease, but not in plasma of normal donors, indicating that such plasma contained soluble CD154 (sCD154). Using a quantitative ELISA method, we found that the plasma of patients with active disease had levels of sCD154 that were significantly higher than those found in plasma of normal donors. Levels of CD154 transcripts in SLE blood lymphocytes correlated with the relative concentrations of sCD154 found in SLE plasma. Furthermore, plasma levels of sCD154 correlated with the titers of anti–double-stranded DNA autoantibody and with clinical disease activity. These studies indicate that sCD154 of patients with SLE may act as a functional ligand for CD40 that is associated with SLE disease activity.

Authors

Kazunori Kato, Ernesto Santana-Sahagún, Laura Z. Rassenti, Michael H. Weisman, Naoto Tamura, Shigeto Kobayashi, Hiroshi Hashimoto, Thomas J. Kipps

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Comparison of the numbers of CD154 transcripts per cell with the measure...
Comparison of the numbers of CD154 transcripts per cell with the measured sCD154 plasma concentration or the intensity of CD154 surface membrane expression on blood mononuclear cells of patients with SLE. The numbers of CD154 transcripts per freshly isolated mononuclear cells of 10 patients with SLE are indicated on the abscissa. (a) Each dot represents the mean plasma concentration of sCD154 detected for each patient, as indicated on the ordinate (picogram per milliliter). These points are plotted against the numbers of CD154 transcripts per cell detected in the mononuclear cells isolated from the whole-blood sample from which each plasma sample was derived. The line depicts the best-fit correlation between the levels of CD154 transcripts per cell and the plasma concentration of sCD154 (Pearson r = 0.779, P = 0.01). (b) Each dot represents the intensity of CD154 membrane expression on the blood mononuclear cells of each patient, indicated on the ordinate as the MFIR of cells stained with anti-CD154 mAb and a control mAb of the same isotype. The line depicts the best-fit correlation between the levels of CD154 transcripts per cell and the intensity of CD154 surface membrane expression (Spearman r = 0.194, P = 0.584).