Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment

Abstract

Introduction: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown.

Methods: Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively.

Results: IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept.

Conclusions: Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.

Figure 1

IL-20 is expressed in PsA and RA synovial tissues. (A) Representative immunohistochemical staining of baseline IL-20 expression in synovial tissue from PsA and RA patients. Arrows indicate expression of IL-20 in both lining and sublining. (B) Quantification of IL-20 expression in RA and PsA synovial tissues. Results are shown as median IOD (integrated optical density)/mm² × 10⁵ of 10 patients with RA and 11 patients with PsA. (C) Double-immunohistochemistry stainings of IL-20 (red) and CD68⁺ macrophages (blue) and CD55⁺ FLS (blue) in PsA synovium. A representative double immunostaining of PsA synovium from one patient is shown. Arrows indicate double-positive cells. Original magnification, ×200. CRP, C-reactive protein; DAS28, disease activity score; ESR, erythrocyte sedimentation rate; SJC, swollen-joint count; TJC, tender-joint count; VAS, visual analogue scale (100 mm).

Figure 2

Alefacept treatment does not affect IL-20 expression in PsA synovium. (A) Representative immunohistochemical staining of IL-20 in the synovium of a PsA patient. (B) Quantification of IL-20 expression in PsA synovium. Results are shown as median IOD (integrated optical density)/mm² × 10⁵ of 11 patients with PsA. (C) Correlation between the expression of IL-20 and the number of CD55⁺ FLSs in PsA synovium. Original magnification, ×200. Each dot represents the mean of the 18 high-power fields per patient per time point. CRP, C-reactive protein; DAS28, disease activity score; ESR, erythrocyte sedimentation rate; SJC, swollen-joint count; TJC, tender-joint count; VAS, visual analogue scale (100 mm).

Figure 3

Decreased IL-20 expression in PsA skin lesions after alefacept treatment. (A) Representative immunohistochemical staining of IL-20 expression in the lesional skin of a PsA patient. (B) Quantification of IL-20 expression in PsA lesional skin. Results are shown as median of semiquantitative score (SQ) of six patients with PsA. (C) IL-20 expression in PsA lesional skin is correlated with disease activity (PASI). All time points are depicted (each dot represents one patient per time point). *Statistical significance, P = 0.04. Original magnification, ×200. CRP, C-reactive protein; DAS28, disease activity score; ESR, erythrocyte sedimentation rate; SJC, swollen-joint count; TJC, tender-joint count; VAS, visual analogue scale (100 mm).