Solving the puzzle of the immunopathogenesis of spondyloarthritis

Dr. Christopher Ritchlin presented an elegant summary of how our evolving knowledge of cytokines’ actions in the immune system are helping to unravel the puzzleof spondyloarthritis (SpA). The implicated “master cytokines” include IL-17, IL-22 and TNF.

There is mounting evidence that these cytokines act in concert to up-regulate inflammation and bone resorption. New transgenic mouse models suggest that transmembrane vs.soluble TNF may drive inflammatory arthritis from to a SpA rather than an RA phenotype.

Also important is the mechanobiology of SpA, with data suggesting that enthesitis and new bone formation are driven by mechanical strain.

The microbiome continues to be an area of exciting research in SpA immunopathogenesis. Microbiome disruptions are commonly seen in SpA. Supporting evidence for microbiomal disruptions includes the links between SpA and inflammatory bowel disease, reactive arthritis, flares of psoriasis with Streptococcal infections, and absence of arthritis in mouse models in germ-free environments.

Finally, there is a suggestion that in PsA, cutaneous nociceptors may promote IL-23 release. This may suggest that development of psoriasis through activation of nociceptors then drives a localized IL-23 response. This may potentially explain why PsA patients may present with such striking ray diversity.

Additional work is continuing to bring these findings from the bench to the bedside.

More reports from ACR 2014