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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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 5

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Relationship between sCD154 plasma concentration and SLE disease activit...
Relationship between sCD154 plasma concentration and SLE disease activity. (a) Described are the measured sCD154 plasma concentrations of control donors (open circles in column 0), SLE patients with low disease activity (SLEDAI between 2 and 9; shaded circles in column labeled 2–9), and patients with active SLE (SLEDAI ≥10; filled circles in the right column labeled ≥10), as indicated on the abscissa (nanogram per milliliter). Each dot represents the measured plasma concentration for an individual subject. The P values, indicating the differences between the mean values for each group, are indicated at the top of the figure. The difference between the inactive and active SLE groups is statistically significant (P < 0.0001). (b) Described are the relationships between measured plasma concentrations of sCD154 (as indicated on the ordinate in nanogram per milliliter) and the anti-dsDNA Ab levels in each of 23 SLE patient samples, as indicated on the abscissa (IU/mL). The line represents the best-fit correlation between the plasma concentrations of sCD154 and the anti-dsDNA Ab levels (Spearman r = 0.758, P < 0.001). Four of the values represent measurements made of serial samples obtained from the same patient (filled squares labeled 1, 2, 3, and 4). Square 1 is the initial sample taken before immune suppressive therapy. Samples for squares 2, 3, and 4 were obtained from the same patient 4, 8, and 17 weeks later, respectively.