TY - JOUR T1 - 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 JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.100454 SP - jrheum.100454 AU - Marek Bielecki AU - Krzysztof Kowal AU - Anna Lapinska AU - Pawel Bernatowicz AU - Lech Chyczewski AU - Otylia Kowal-Bielecka Y1 - 2010/09/01 UR - http://www.jrheum.org/content/early/2010/08/29/jrheum.100454.abstract N2 - 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 antitopoisomerase 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. Conclusion 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. ER -