Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis

Abstract

At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/axial forms belonging to SpA and polyarticular forms resembling rheumatoid arthritis (RA). To address this issue with regard to peripheral synovitis, we compared the synovial characteristics of PsA with those of ankylosing spondylitis (AS)/undifferentiated SpA (USpA) and RA, and compared the synovium of oligoarticular versus polyarticular PsA. Synovial biopsies were obtained from patients with RA, nonpsoriatic SpA (AS + USpA), and oligoarticular and polyarticular PsA. The histological analysis included examination(s) of the lining layer thickness, vascularity, cellular infiltration, lymphoid aggregates, plasma cells and neutrophils. Also, we performed immunohistochemical assessments of CD3, CD4, CD8, CD20, CD38, CD138, CD68, CD163, CD83, CD1a, CD146, alphaVbeta3, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, S100A12, intracellular citrullinated proteins and major histocompatibility complex (MHC)-human cartilage (HC) gp39 peptide complexes. Comparing SpA (PsA + AS + USpA) with RA, vascularity, and neutrophil and CD163+ macrophage counts were greater in SpA (P < 0.05), whereas lining layer thickness and the number of CD83+ dendritic cells were greater in RA (P < 0.05). In RA, 44% of samples exhibited positive staining for intracellular citrullinated proteins and 46% for MHC-HC gp39 peptide complexes, whereas no staining for these markers was observed in SpA samples. We excluded influences of disease-modifying antirheumatic drug and/or corticosteroid treatment by conducting systematic analyses of treated and untreated subgroups. Focusing on PsA, no significant differences were observed between PsA and nonpsoriatic SpA. In contrast, vascularity (P < 0.001) and neutrophils were increased in PsA as compared with RA (P = 0.010), whereas staining for intracellular citrullinated proteins and MHC-HC gp39 peptide complexes was exclusively observed in RA (both P = 0.001), indicating that the same discriminating features are found in PsA and other SpA subtypes compared with RA. Exploring synovial histopathology between oligoarticular and polyarticular PsA, no significant differences were noted. Moreover, intracellular citrullinated proteins and MHC-HC gp39 peptide complexes, which are specific markers for RA, were observed in neither oligoarticular nor polyarticular PsA. Taken together, these data indicate that the synovial histopathology of PsA, either oligoarticular or polyarticular, resembles that of other SpA subtypes, whereas both groups can be differentiated from RA on the basis of these same synovial features, suggesting that peripheral synovitis in PsA belongs to the SpA concept.

Figure 1

Synovial histology in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and nonpsoriatic spondyloarthropathy (ankylosing spondylitis [AS] + undifferentiated spondyloarthropathy [USpA]). Synovial biopsies from RA, PsA and spondyloarthropathy (SpA; AS/USpA) patients were scored on a semiquantitative scale (0–3) by two independent observers. Representative sections of RA and PsA and nonpsoriatic SpA synovium are shown, and the corresponding semiquantitative score for each picture is indicated. The evaluated parameters included synovial lining layer thickness, CD83⁺ dendritic cells, CD38⁺ plasma cells, degree of vascularity, number of neutrophils (polymorphnuclear neutrophils [pmn]) and CD163⁺ macrophages.

Figure 2

Synovial expression of S100A12 in psoriatic arthritis (PsA), nonpsoriatic spondyloarthropathy (SpA; ankylosing spondylitis [AS] + undifferentiated spondyloarthropathy [USpA]) and rheumatoid arthritis (RA). (a) PsA: lining = 0, sublining = 1 (original magnification 640×); (b) nonpsoriatic SpA: lining = 0, sublining = 2 (original magnification 640×); and (c) RA: lining = 0, sublining = 2 (original magnification 640×).