Abstract
IntroductionPsoriatic 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.MethodsEleven 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.ResultsIL-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.ConclusionsConceivably, 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.
Highlights
Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis
Double staining of inflamed PsA synovium showed that CD68+ macrophages and CD55+ fibroblast-like synoviocyte (FLS) coexpress IL-20 (Figure 1C)
Alefacept treatment does not affect IL-20 expression in PsA synovium As previously described, alefacept treatment resulted in clinical improvement and in a reduction of CD4+ T cells and CD68+ macrophages in the synovial infiltrate [4]
Summary
Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept was the first of the biologic agents to be approved in the United States for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy This fully human fusion protein inhibits activation of memory T cells (CD45RO+), a subpopulation of lymphocytes that plays a critical role in the pathogenesis of psoriasis [2]. This therapy has been shown to be effective in patients with psoriasis [3], and it has some efficacy in PsA [4,5] compared with anti-TNF therapy. As determined by the American College of Rheumatology 20 (ACR20) response at week 24, was achieved by a significantly greater proportion of patients receiving alefacept plus methotrexate (54%) compared with those receiving placebo plus methotrexate (23%), but proportions of patients achieving ACR50 and ACR70 responses at week 24 were not significantly different in a randomized, double-blind, placebo-controlled study in 185 PsA patients [5]
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