Elevated levels and functional capacity of soluble CD40 ligand in systemic lupus erythematosus sera.
OBJECTIVE
To measure soluble CD40 ligand (sCD40L) in sera from patients with systemic lupus erythematosus (SLE) and to study the functional capacity of sCD40L in mediating B cell activation.


METHODS
A 2-site enzyme-linked immunosorbent assay (ELISA) was used to measure sCD40L in the sera of 66 SLE patients, 30 disease control patients, and 23 healthy subjects. Induction of B cell activation antigen expression was used to assess the functional capacity of sCD40L in SLE sera.


RESULTS
The mean concentration of sCD40L was statistically significantly higher (P < 0.0001) in SLE patients than in disease controls or healthy subjects, and segregation of SLE patients by severe, moderate, or mild extent of disease showed a relationship between disease severity and sCD40L concentration. Western blot analysis demonstrated the presence of the 18-kd band of sCD40L in SLE sera, and the results of a 1-site ELISA protocol suggested that some of the product in SLE sera was present in dimer or trimer form. Functional studies showed that 10 ng/ml of recombinant CD40L, a level present in some SLE sera, induced increased expression of CD95 on B cells. Several SLE sera also induced CD95 or CD86 on Ramos B cells, a result that was inhibited by anti-CD40L monoclonal antibodies.


CONCLUSIONS
The soluble form of CD40L is present in the sera of most patients with SLE and may have the capacity to mediate B cell activation. Aberrant expression of CD40L might be predicted to result in activation of bystander B cells, including those that have encountered self antigens, and to contribute to autoantibody secretion.
D000954:Antigens, Surface / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000097:blood / Q000737:chemistry; D023201:CD40 Ligand; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008562:Membrane Glycoproteins / Q000097:blood* / Q000494:pharmacology; D008970:Molecular Weight; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility