Dynamic visualization of a joint-specific autoimmune response through positron emission tomography

Abstract

In the K/BxN mouse model of rheumatoid arthritis, the transfer of autoantibodies specific for glucose-6-phosphate isomerase (GPI) into naïve mice rapidly induces joint-specific inflammation similar to that seen in human rheumatoid arthritis. The ubiquitous expression of GPI and the systemic circulation of anti-GPI immunoglobulin G (IgG) seem incongruous with the tissue specificity of this disease. By using PET (positron emission tomography), we show here that purified anti-GPI IgG localizes specifically to distal joints in the front and rear limbs within minutes of intravenous injection, reaches saturation by 20 min and remains localized for at least 24 h. In contrast, control IgG does not localize to joints or cause inflammation. The rapid kinetics of anti-GPI IgG joint localization supports a model in which autoantibodies bind directly to pre-existing extracellular GPI in normal healthy mouse joints.