Fig. 2.

Mechanisms involved in early phases of SpA

Injured tissue may activate innate immune responses in many ways. These include fragments of extracellular matrix proteins that collectively activate TLRs, among others. Injured or stressed cells secrete or release proteins that once outside the nucleus can also prime innate immunity. Necrotic cell death also releases nuclear contents that once in the extracellular environment may serve as strong activators of innate immunity and includes RNA and DNA, proteins including HMGB1, and uric acid and HSP, among others. Collectively these likely activate enthesis and bone resident immune cell populations. It is considered that the dysregulated innate immunity in the gut and the spine increase the chances of innate immune dysfunction and clinical development of AS. DAMPs: danger associated molecular patterns; PRR: pattern recognition receptors; HMGB-1: high mobility group protein B1; ILC: Innate lymphoid cells; MAIT: mucosal associated invariant T cell.