title: Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment.
abstract: BACKGROUND
  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.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Lebre
authors.forename: Christina L
authors.initials: CL
authors.lastname: Jonckheere
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Kraan
authors.forename: Arno W R
authors.initials: AW
authors.lastname: van Kuijk
authors.forename: Jan D
authors.initials: JD
authors.lastname: Bos
authors.forename: Menno
authors.initials: M
authors.lastname: de Rie
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000328:Adult; D000077944:Alefacept; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D018958:CD55 Antigens / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D000097382:CD68 Molecule
chemical_list: D000077944:Alefacept; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018958:CD55 Antigens; D003879:Dermatologic Agents; D007378:Interleukins; D011993:Recombinant Fusion Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C422042:interleukin 20