title: Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis.
abstract: BACKGROUND
  Psoriatic arthritis (PsA) is a distinctive inflammatory arthritis which may typically develop in a subgroup of individuals suffering from psoriasis. We recently described progranulin autoantibodies (PGRN-Abs) in the sera of patients with different autoimmune diseases including seronegative polyarthritis. In the present study we investigated the occurrence of PGRN-Abs in PsA.
  
  
  METHODS
  PGRN-Abs were determined in 260 patients with PsA, 100 patients with psoriasis without arthritic manifestations (PsC) and 97 healthy controls using a recently described ELISA. PGRN plasma levels were determined from subgroups by a commercially available ELISA-kit. Possible functional effects of PGRN-antibodies were analysed in vitro by tumour necrosis factor (TNF)-α mediated cytotoxicity assays using WEHI-S and HT1080 cells.
  
  
  RESULTS
  PGRN-Abs were detected with relevant titres in 50/260 (19.23%) patients with PsA, but in 0/100 patients with psoriasis without arthritic manifestations (P = 0.0001). All PGRN-Abs belonged to immunoglobulin G (IgG). PGRN-Abs were significantly more frequent in PsA patients with enthesitis or dactylitis. PGRN-Abs were also more frequent in PsA patients receiving treatment with TNF-α-blockers than in patients treated without TNF-α-blockers (20.8% versus 17.4%; P = 0.016). PGRN plasma levels were significantly lower in PGRN-Ab-positive patients with PsA than in healthy controls and patients with psoriasis without arthritic manifestations (P < 0.001), indicating a neutralizing effect of PGRN-Abs. Moreover cytotoxicity assays comparing PGRN-antibody positive with negative sera from matched patients with PsA, clearly showed a proinflammatory effect of PGRN antibodies.
  
  
  CONCLUSIONS
  Neutralizing PGRN-Abs occur with relevant titres in a subgroup of patients with PsA, but not in patients without arthritic manifestations (PsC). PGRN-Ab-positive patients had more frequent enthesitis or dactylitis. TNF-α-induced cytotoxicity assays demonstrated that the protective effects of progranulin were inhibited by serum containing PGRN-Abs. This suggests that PGRN-Ab might not only be useful as a diagnostic and prognostic marker, but may provide a proinflammatory environment in a subgroup of patients with PsA.
authors: Lorenz
authors: L
authors: Thurner
authors: Marina
authors: M
authors: Zaks
authors: Klaus-Dieter
authors: KD
authors: Preuss
authors: Natalie
authors: N
authors: Fadle
authors: Evi
authors: E
authors: Regitz
authors: Mei Fang
authors: MF
authors: Ong
authors: Michael
authors: M
authors: Pfreundschuh
authors: Gunter
authors: G
authors: Assmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015535:Arthritis, Psoriatic / Q000097:blood* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins