Heightened intrathecal release of soluble CD137 in patients with multiple sclerosis

Human CD137 (ILA/4-1BB), a member of the tumour necrosis factor (TNF) receptor family, regulates the activation and proliferation of immune cells, and may induce apoptosis (programmed cell death) of activated lymphocytes. A soluble form of CD137 (sCD137) released by activated lymphocytes may interfere with the activities of the membrane-bound CD137. This study reports the detection of significantly high intrathecal and systemic levels of sCD137 in patients with clinically active multiple sclerosis (MS) when compared with corresponding levels from patients with clinically stable MS or those with inflammatory and non-inflammatory neurological disorders, or from healthy individuals. Intrathecal concentrations of sCD137 in patients with active MS correlate with the intrathecal release of the soluble death receptor protein Fas, but not with the release of interleukin-2, TNF or the synthesis of immunoglobulins G and M. Results presented here suggest that heightened release of sCD137 is a feature of clinically active MS.