title: Increased production of a proliferation-inducing ligand (APRIL) by peripheral blood mononuclear cells is associated with antitopoisomerase I antibody and more severe disease in systemic sclerosis.
abstract: OBJECTIVE
  A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor (TNF) family, plays a crucial role in the survival of peripheral B cells, and may contribute to the pathogenesis of systemic sclerosis (SSc) through upregulation of autoantibody production and maintenance of autoimmune phenomena. We evaluated the capacity of peripheral blood mononuclear cells from patients with SSc (SSc-PBMC) to produce APRIL; and investigated correlations between production of APRIL by SSc-PBMC and clinical and laboratory features of the disease.
  
  
  METHODS
  PBMC from 20 patients with SSc and 14 healthy subjects were incubated in fetal calf serum-supplemented RPMI medium. APRIL levels were determined in cell culture supernatants by ELISA.
  
  
  RESULTS
  PBMC from patients with SSc produced significantly more APRIL (961 ± 151 pg/ml/10⁵ cells) than control PBMC (798 ± 219 pg/ml/10⁵ cells; p < 0.01). In patients with SSc, increased production of APRIL was associated with the presence of diffuse skin involvement, scleroderma lung disease, peripheral vasculopathy, greater capillary damage on capillaroscopy, and presence of anti-topoisomerase I (anti-topo I) antibodies. Multivariate regression analysis revealed anti-topo I antibodies as the only independent predictor of high production of APRIL by PBMC.
  
  
  CONCLUSIONS
  Production of APRIL is increased in SSc-PBMC and is associated with the presence of anti-topo I antibodies and more severe disease. Targeting the APRIL pathway might represent a therapeutic possibility for treatment of patients with SSc, in particular those with anti-topo I antibodies.
authors.affiliation: Department of Orthopedics and Traumatology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bielecki
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kowal
authors.forename: Anna
authors.initials: A
authors.lastname: Lapinska
authors.forename: Pawel
authors.initials: P
authors.lastname: Bernatowicz
authors.forename: Lech
authors.initials: L
authors.lastname: Chyczewski
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002478:Cells, Cultured; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology*; D012720:Severity of Illness Index; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D004264:DNA Topoisomerases, Type I