Therapeutic Effect of IVIG on Inflammatory Arthritis in Mice Is Dependent on the Fc Portion and Independent of Sialylation or Basophils

• DOI: 10.4049/jimmunol.1301611
• Publication Date: 2014-04-24T03:17:44Z
• Authors: Ian K Campbell; Sylvia Miescher; Donald R Branch; Patrick J Mott; Alan H Lazarus; Dongji Han; Eugene Maraskovsky; Adrian W Zuercher; Anton Neschadim; Danila Leontyev; Brent S McKenzie; Fabian Käsermann
• Keywords: Therapeutic effect; Inflammatory arthritis; Mechanism of Action

Abstract High-dose i.v. Ig (IVIG) is used to treat various autoimmune and inflammatory diseases; however, the mechanism of action remains unclear. Based on K/BxN serum transfer arthritis model in mice, IVIG suppression inflammation has been attributed a involving basophils binding highly sialylated IgG Fc DC-SIGN–expressing myeloid cells. The requirement for sialylation was examined collagen Ab-induced (CAbIA) models mice. (1–2 g/kg body weight) suppressed when given prophylactically. same doses were also effective CAbIA subsequent disease induction. In this therapeutic model, anti-inflammatory effect dependent but not F(ab′)2 fragments. Removal sialic acid residues by neuraminidase had no impact activity or Treatment mice with basophil-depleting mAbs did abrogate either IVIG. Our data confirm benefit fail support significance basophil involvement therapy.