Figure 3.

Comparison of the principle phenotypic features of rat and human spondyloarthritis. Rats with 20–40 or more copies of the HLA-B27 transgene in the presence of 15–30 copies of hβ₂m develop spondyloarthritis-like inflammatory disease spontaneously, beginning shortly after weaning. IBD develops in virtually 100% of HLA-B27 transgenic rats, while peripheral and axial arthritis occur with significantly reduced frequency, and generally after several months of age (Rat SpA-1). Human spondyloarthritis (undifferentiated spondyloarthritis classified various ways) exhibits a more equal mix of IBD (Crohn’s disease and ulcerative colitis), and peripheral and axial arthritis. Psoriatic arthritis and psoriatic spondylitis are not represented here. Nevertheless, development of skin and nail changes have been reported in HLA-B27 transgenic rats and psoriatic skin lesions occur in IL-23 overexpressing mice. Human AS represents the other end of the spectrum where axial arthritis in the form of radiographic sacroiliitis occurs in 100% of affected individuals (by definition), and peripheral arthritis and overt IBD are significantly less frequent. However, sub-clinical IBD occurs in close to 70% of individuals with AS, with overt IBD in ~6%. A second rat spondyloarthritis model (SpA-2; not shown) occurs with forced overexpression of additional hβ₂m (35 transgene copies) in rats with 20 or more copies of HLA-B27 and at least 50 copies of hβ₂m. Rat SpA-2 does not require IBD, although this phenotypic feature still occurs in high copy HLA-B27 transgenic rats with additional hβ₂m. Both peripheral and axial arthritis occur at much higher frequency and severity with additional hβ₂m, but arthritis is primarily restricted to male rats and requires epididymoorchitis.