We studied whether soluble CD40 ligands (sCD40L) are removed by means of double filtration plasmapheresis (DFPP), and the removal may help decrease activity of systemic lupus erythematosus (SLE). We studied 10 female patients with active SLE. Double filtration plasmapheresis was conducted one or two times per week. Plasma sCD40L levels were measured before and after each round of DFPP and throughout the treatment course. The plasma sCD40L level of SLE patients was significantly higher (14.09 +/- 18.88 ng/mL) than that of healthy individuals (0.19 +/- 0.20 ng/mL; P < 0.0001). In the SLE patients, plasma sCD40L levels were significantly lower following DFPP (P = 0.0251). The plasma waste from DFPP of an SLE patient was subjected to gel filtration, and the sCD40L concentration in each fraction was measured. We observed a peak in the fraction corresponding to > or =60 kDa. These results indicate that trimers and higher order complexes of sCD40L are removed during DFPP. Plasma sCD40L level and SLE disease activity index (SLEDAI) were decreased following the treatment course (mean 9.3 months). sCD40L exists as both a monomer and trimer in the plasma of SLE patients. The trimer as well as higher-order compounds can be removed via DFPP. It was thought that removal of sCD40L via DFPP may be useful for improving the overall condition of SLE.