A soluble form of CD5 comprises the three ectodomains and is generated after T-cell receptor activation by proteolytic excision of membrane-bound CD5.23 Overexpression of soluble CD5 leads to more severe forms of disease in animal models of arthritis and neuroinflammation, suggesting a role in autoimmune disease.24 TNFRSF9 (also known as CD137) is a potent costimulatory receptor and several agonistic anti-TNFRSF9 antibodies are currently in clinical trials for tumour immunotherapy. This evidence concerns the gene TNFRSF9 and arthritic joint disease.