Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis

Abstract

Anti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21 sera from patients with acute systemic vasculitis following incubation with normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive binding assays using F(ab')2 fragments from IVIg and affinity chromatography of ANCA IgG on Sepharose-bound F(ab')2 fragments from IVIg. Co-incubation of sera from patients with acute systemic vasculitis with paired autologous remission stage sera also resulted in inhibition of ANCA activity in acute sera. Remission sera contain IgM and IgG capable of interacting with beta and or alpha idiotypes of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of expression of ANCA activity in whole serum from patients in remission from systemic vasculitis, which were found to contain high titres of ANCA IgG. These observations suggest that remission of systemic vasculitis is associated with the generation of anti-idiotypes against autoantibodies rather than the suppression of production of ANCA autoantibodies. IVIg may modulate the activity of systemic vasculitis in vivo.