Dynamic visualization of a joint-specific autoimmune response through positron emission tomography.
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.
Wipke
Brian T
BT
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wang
Zheng
Z
Kim
Joonyoung
J
McCarthy
Timothy J
TJ
Allen
Paul M
PM
D000818:Animals; D000843:Ankle Joint / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011859:Radiography; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods
D001324:Autoantigens; D003301:Copper Radioisotopes; D007074:Immunoglobulin G; D005956:Glucose-6-Phosphate Isomerase