Detection of Cross-Reactive Idiotypes in the Serum of Patients with Bullous Pemphigoid

Abstract

To further characterize the circulating antibasement membrane zone (antiBMZ) antibodies present in the sera of patients with bullous pemphigoid (BP), we have generated a mouse monoclonal anti-idiotypic antibody (antiId 3-17) specific for an IgG antiBMZ antibody. AntiId 3-17 is specific for an idiotype expressed on antiBMZ IgG in the serum of a patient with BP, and not expressed on pooled normal human IgG or IgG from patients with other autoimmune skin diseases. AntiId 3-17 binds to non-reduced, but not reduced, antiBMZ IgG on immunoblot, suggesting that the idiotype is composed of a conformational epitope expressed on native antibody. By a competitive inhibition ELISA, antiId 3-17 detects a cross-reactive idiotype (CRI) expressed in 18 of 50 (36%) of the sera of patients with BP, but in the sera of only 1 of 50 (2%) normal blood bank controls (p less than 0.001, Fisher's exact test) and 1 of 12 (8%) patients with pemphigus (p = 0.005). Thus, antiId 3-17 recognizes a public idiotype on a native antiBMZ antibody from a patient with BP, which is expressed in the sera of 36% of the unrelated patients with BP studied.