Abstract

Psoriatic arthritis (PsA) is a heterogeneous disease that affects multiple organ systems including the peripheral and axial joints, entheses and nails. PsA is associated with significant comorbidities including cardiovascular, metabolic, and psychiatric diseases. The pathogenesis of PsA is complex and involves genetic, immunologic and environmental factors. Recent evidence suggests the heritability for PsA to be stronger and distinct from that of PsC. Prominent genes identified via GWAS for PsA include HLA-B/C, HLAB, IL12B, IL23R, TNP1, TRAF3IP3, and REL. We review the genetics of psoriatic arthritis and discuss the role of the innate immune system as important in the pathogenesis of PsA by focusing on key signaling pathways and cellular makeup. Understanding the candidate genes identified in PsA highlights pathways of critical importance to the pathogenesis of psoriatic disease including the key role of the innate immune response, mediated through IL-23/IL-17 axis, RANK and NFκB signaling pathways.

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