OBJECTIVES: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti-platelet antibodies induce platelet destruction owing to an imbalanced immune response. Several studies have established that B cells play an important role in the production of anti-platelet antibodies and that dendritic cells (DC) are professional antigen-presenting cells of the immune system that may lead to the development of autoantibody through B cells. We aimed at investigating the role of B cells and DC in the pathogenesis of ITP through B-lymphocyte stimulator (BlyS) and toll-like receptor 7 (TLR7) signals. METHODS: Twenty-two patients with ITP and 20 healthy controls were enrolled in this study. Serum BlyS, its mRNA and TLR7 mRNA were measured using ELISA kits or RT-PCR, and CD14(+) or CD19(+) monocytes were investigated for the pathogenesis of ITP with in vitro culture systems. RESULTS: We demonstrated that serum BlyS levels in patients with ITP were significantly higher than those in healthy controls and that there was a positive correlation between serum BlyS levels and glycoprotein-specific antibody levels in patients with ITP. We found that TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in patients with ITP. Dendritic cells stimulated with R848 (TLR7 ligand) are able to produce vast amounts of BlyS, which is crucial for B-cell survival, proliferation and differentiation, and increase anti-platelet antibodies production in in vitro coculture systems. CONCLUSIONS: These findings provide new insights into the pathogenesis of ITP by which TLR7 regulates DC-dependent B-cell responses through BlyS.
OBJECTIVES: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti-platelet antibodies induce platelet destruction owing to an imbalanced immune response. Several studies have established that B cells play an important role in the production of anti-platelet antibodies and that dendritic cells (DC) are professional antigen-presenting cells of the immune system that may lead to the development of autoantibody through B cells. We aimed at investigating the role of B cells and DC in the pathogenesis of ITP through B-lymphocyte stimulator (BlyS) and toll-like receptor 7 (TLR7) signals. METHODS: Twenty-two patients with ITP and 20 healthy controls were enrolled in this study. Serum BlyS, its mRNA and TLR7 mRNA were measured using ELISA kits or RT-PCR, and CD14(+) or CD19(+) monocytes were investigated for the pathogenesis of ITP with in vitro culture systems. RESULTS: We demonstrated that serum BlyS levels in patients with ITP were significantly higher than those in healthy controls and that there was a positive correlation between serum BlyS levels and glycoprotein-specific antibody levels in patients with ITP. We found that TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in patients with ITP. Dendritic cells stimulated with R848 (TLR7 ligand) are able to produce vast amounts of BlyS, which is crucial for B-cell survival, proliferation and differentiation, and increase anti-platelet antibodies production in in vitro coculture systems. CONCLUSIONS: These findings provide new insights into the pathogenesis of ITP by which TLR7 regulates DC-dependent B-cell responses through BlyS.
Authors: Milka Koupenova; Olga Vitseva; Christopher R MacKay; Lea M Beaulieu; Emelia J Benjamin; Eric Mick; Evelyn A Kurt-Jones; Katya Ravid; Jane E Freedman Journal: Blood Date: 2014-04-22 Impact factor: 22.113