One of the most satisfying aspects of the genome-wide association studies conducted in patients withankylosing spondylitis (AS) has been the large numberof genes that have been shown to affect susceptibility todisease (1). The first gene of this kind to be identifiedwas the interleukin-23 receptor (IL-23R). A potentialrole of IL-23 signaling in the pathogenesis of AS wasfurther supported by additional genes associated withAS, including the following: 1) IL-12B, which encodesthe 40-kd (p40) chain, a component of both IL-12 andIL-23; in the latter, it is paired with a 19-kd protein(p19); 2) caspase recruitment domain 9 (CARD-9),which encodes a major signaling intermediate in thepathway whereby fungal products induce IL-23 produc-tion from dendritic cells (DCs); and 3) STAT-3, whichencodes the major signaling molecule activated by theIL-23R. Additionally, there are suggested associations(which need further confirmation) with JAK-2, whichencodes another important signaling molecule down-stream of IL-23R, and prostaglandin E receptor 2 sub-type EP