Basic synovial biology and immunopathology in psoriatic arthritis.
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy with a well recognized propensity for aggressive bone erosions. In some individuals, however, periarticular bone mineralization is maintained, and there is often associated new bone formation with periostitis and frank ankylosis; thus PsA manifests, in different individuals, reciprocal patterns of joint pathology suggesting a disorder of bone remodeling. Recent key scientific advances will be briefly reviewed including T cell, B cell, human leukocyte antigen associations; and the importance of neoangiogenesis, vascularity, and adhesion molecules in conjunction with inflammatory infiltrates and cytokine expression. Finally, the mechanisms of abnormal bone remodeling are discussed, including mediators of osteoclastogenesis such as RANK ligand and molecular signaling pathways including Dickkop-1 and bone morphogenetic proteins. Although much has been learned about the pathogenesis of PsA, much remains to be defined regarding the mechanisms linking synovial biology and immunopathology to different disease outcomes. Identifying key differentiating factors between the diverse PsA phenotypes, correlating findings with the rapidly advancing field of ultrasound image acquisition, and delineating the cellular and molecular mechanisms of abnormal bone remodeling in combination should enable the development of improved prognostic algorithms. This in turn should facilitate the targeting of expensive (about pound10k/patient/year) and potentially toxic yet effective biologics to patients most in need.
Robinson
Helena
H
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Kelly
Stephen
S
Pitzalis
Costantino
C
D015535:Arthritis, Psoriatic / Q000276:immunology* / Q000503:physiopathology; D016723:Bone Remodeling / Q000276:immunology* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009389:Neovascularization, Pathologic / Q000276:immunology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D013583:Synovial Membrane / Q000098:blood supply / Q000276:immunology* / Q000503:physiopathology
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human