Psoriatic arthritis: from pathogenesis to therapy

Abstract

Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.

Figure 1

Inheritance of psoriatic arthritis. Two families are shown in which psoriatic arthritis (half-filled shapes) appears to exhibit a different pattern of inheritance. In the first it appears that the disease is inherited as a simple dominant, although the absence of disease in the parents is not consistent with this. In the second, there is an interplay between the psoriasis phenotype (quarter-filled shapes) in the parent and child in the third generation, and the instances of psoriatic arthritis in the second.

Figure 2

Representation of the complex relationship between HLA susceptibility and psoriatic arthritis. The areas on the diagram are not exactly drawn to scale. The right side of the diagram depicts the presence of the Cw*0602 allele in healthy people, its strong association with cutaneous psoriasis susceptibility, and the fact that approximately 40% of those with psoriasis lack Cw*0602. The left side depicts the almost complete association of B*27 with ankylosing spondylitis. Psoriatic arthritis, which includes psoriasis plus the musculoskeletal phenotype, is shown as the thick rimmed circle. Both Cw*0602 and B*27 alleles contribute independently to psoriatic arthritis susceptibility. HLA, human leukocyte antigen.

Figure 3

Immunopathogenesis of psoriatic arthritis. A proposed model for psoriatic arthritis immunopathogenesis is illustrated in which a genetically primed individual is exposed to a bacterial, stress, or entheseal-related peptide. This in turn activates the innate immune response, resulting in CD8 infiltration and chemokine/cytokine release. The process is amplified with angiogenesis and cellular infiltration of involved tissues. HLA and other genes expressed may determine the exact pattern of tissue involvement. HLA, human leukocyte antigen; MHC, major histocompatibility complex; NKR, natural killer cell receptor; TCR, T-cell receptor; TLR, Toll-like receptor.