Elevated levels and functional capacity of soluble CD40 ligand in systemiclupus erythematosus sera

Objective. To measure soluble CD40 ligand (sCD40L) in sera from patients wi th 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 mea sure sCD40L in the sera of 66 SLE patients, 30 disease control patients, an d 23 healthy subjects. Induction of B cell activation antigen expression wa s used to assess the functional capacity of sCD40L in SLE sera. Results. The mean concentration of sCD40L was statistically significantly h igher (P < 0.0001) in SLE patients than in disease controls or healthy subj ects, and segregation of SLE patients by severe, moderate, or mild extent o f disease showed a relationship between disease severity and sCD40L concent ration, Western blot analysis demonstrated the presence of the 18-kd band o f 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. F unctional studies showed that 10 ng/ml of recombinant CD40L, a level presen t in some SLE sera, induced increased expression of CD95 on B cells, Severa l SLE sera also induced CD95 or CD86 on Ramos B cells, a result that was in hibited by anti-CD40L monoclonal antibodies. Conclusion. The soluble form of CD40L is present in the sera of most patien ts with SLE and may have the capacity to mediate B cell activation. Aberran t expression of CD40L might be predicted to result in activation of bystand er B cells, including those that have encountered self antigens, and to con tribute to autoantibody secretion.