Pathogenesis of psoriatic arthritis

Abstract

Purpose of review: Heterogeneity in clinical presentation and disease course has hindered understanding of disease mechanisms in psoriatic arthritis, but recent studies have provided insights into pathogenesis. This review examines relevant animal models and genetic factors implicated in disease susceptibility. Also, recent reports on mechanisms related to synovial and entheseal inflammation are discussed.

Recent findings: Two transgenic mouse models (amphiregulin, STAT-3) were reported that have features of psoriatic arthritis and psoriasis respectively. Genetic studies did not find associations between psoriatic arthritis and several class I major histocompatibility complex alleles, the caspase-activating recruitment domain 15 domain, or the major histocompatibility complex class I chain-related gene A9 allele, in sharp contrast to previous reports. The striking association of psoriatic arthritis with mutations in the killer immunoglobulin receptors on natural killer cells is particularly exciting but needs further study. Psoriatic arthritis has histopathologic features that are more characteristic of other forms of spondyloarthritis than rheumatoid arthritis. Moreover, several of these features correlate with clinical disease activity. Matrix metalloproteinases are strongly expressed in psoriatic arthritis synovium, and serum matrix metalloproteinases-3 may be a reliable biomarker for monitoring disease response. Finally, the concept of an 'enthesis organ' may explain the magnetic resonance imaging findings and clinical signs of psoriatic enthesitis and dactylitis.

Summary: Recent findings highlight the importance of innate immune mechanisms in disease pathogenesis. Moreover, psoriatic arthritis and rheumatoid arthritis synovium have divergent histopathologic features that indicate distinct disease mechanisms. The generation of appropriate animal models coupled with reliable biomarkers will result in a deeper understanding of disease pathogenesis and will facilitate the identification of new therapeutic targets.