As results of these experiments demonstrated, mice receiving serum or PBMCs from patients with axial disease demonstrated evidence of cervical and thoracic kyphosis, bone erosion and osteoproliferation in the tail; micro-CT scans showed bone resorption and bone fusion of the sacroiliac joints and lumbar spine. Further, histopathological studies showed inflammatory infiltrates with CD3 and CD8 T cells expressing both TNF and IL-17. These findings did not occur in mice receiving sera or PBMCs from patients with PsA but without axial involvement.
Although the number of mice in this study was small, the results are striking and suggest a new way to explore the mechanisms of axial disease in patients with PsA. One wonders whether similar changes would occur in patients with axial spondylitis without psoriasis or PsA and whether the active component in sera is IgG. Whatever the outcome of future studies, the results will be very interesting.
6. From Skin-Limited Disease to Joint Involvement
Raimondo et al., Abstract 17576
PsA occurs in approximately 30% of patients with PsO. While this finding suggests a strong mechanistic link between events in the skin and those in the joint, the basis for the transition of disease to skin is unknown. In this clever study, Raimondo et al. tracked skin-derived cells in a model of psoriasis based on overexpression of the cytokine IL-23 (IL23OE) in KAEDE transgenic mice. The KAEDE mice express a photoconvertible protein that undergoes a green to red color change when exposed to ultraviolet (UV) radiation. Thus, by exposing skin of the mice with psoriasis to UV light, a population of red cells is created to allow their detection in the joints of the mice by fluorescence microscopy and flow cytometry.
The results of this study show that immune cells can migrate from the skin to the joint, although their presence in the synovium did not directly correlate with the presence of arthritis. Rather, in mice with arthritis, the myeloid cells differentiated into pro-inflammatory macrophages; in the resistant mice, these cells showed an M2-like anti-inflammatory phenotype. In these differentiation pathways, CD200+ synovial fibroblasts appeared to be important in determining macrophage fate and, therefore, the onset of arthritis.
These studies have two important messages: 1) Immune cells can migrate from the skin to the joint in a skin-joint axis, and 2) synovial fibroblasts have a key role in influencing macrophage differentiation.
Because skin disease precedes joint disease in most patients, it will be interesting to determine whether the type of therapy for skin disease (i.e., topical therapy vs. DMARDs) affects the development of arthritis.
