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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

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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 1

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Changes in surface antigen phenotype of Ramos B cells after culture in h...
Changes in surface antigen phenotype of Ramos B cells after culture in human plasma depleted of fibrinogen. Ramos B cells were cultured in media supplemented with 50% human plasma either without (a and b) or with (c and d) a neutralizing mAb specific for CD154. The cells were examined for expression of CD54 (a and c) or CD95 (b and d) using flow cytometry. The histograms depict the relative cell number and the logarithmic fluorescence intensity. Open histograms represent staining of Ramos cells with an isotype control mAb. Hatched and filled histograms depict the staining of Ramos cells with antigen-specific mAb after culture in plasma from a control donor (NOR-plasma) or patient with SLE (SLE-plasma), respectively.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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