HLA-B27- and ERAP1-negative disease is unlikely to be caused by a similar mechanism, and the fact that the overexpression of TNF alone is sufficient to cause spondyloarthritis in mice suggests that overexpression or signaling by proinflammatory cytokines alone may be sufficient to cause ankylosing spondylitis [42]. This evidence concerns the gene ERAP1 and spondyloarthropathy.