Although increased production of soluble isoforms could be expected to reduce signaling through reducing both cell surface expression and offering alternative ligand binding, soluble receptors have also been shown to potentially increase signaling through increasing the half-life of ligands (e.g. potentially for soluble CD40L) [43], and further work is required to ascertain if soluble CD40 levels are indeed relatively increased in MS patients, as these data suggest. Here, CD40 is linked to myeloid sarcoma.