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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Figure 3

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ELISA to detect sCD154 concentrations in human plasma. (a) A standard cu...
ELISA to detect sCD154 concentrations in human plasma. (a) A standard curve for serial dilutions of a recombinant sCD154 placed into separate wells of a microtiter plate precoated with anti-CD154 mAb (TRAP1). Bound recombinant sCD154 was detected using a non–cross-reacting, biotinylated anti-CD154 mAb (M90). The mean absorbance of triplicate wells is indicated on the ordinate, and the logarithmic concentration (picograms per milliliter) of the recombinant sCD154 is provided on the abscissa. (b) Indicated are the measured concentrations of sCD154 in plasma isolated at various times after phlebotomy from whole blood kept at room temperature (filled circles) or at 4°C (open circles). The calculated concentration of sCD154 is listed on the ordinate (picograms per milliliter), and the time after phlebotomy prior to plasma separation is listed in hours on the abscissa. Each point represents the mean value of triplicate wells, and the error bars indicate the SE. (c) The concentrations of sCD154 (picograms per milliliter) that were detected in the plasma of each of 21 control donors (open circles) or 26 patients with SLE (filled circles) are indicated. Each point represents the concentration found in a single donor. The bar indicates the mean concentration for the healthy and SLE groups. The numbers indicate the mean concentration for each group ± SD about the mean. A dotted line represents the mean + 3 SD of sCD154 in control donors. The P value is calculated for the difference between the means of the 2 groups (P < 0.0001).