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

Brian T. Wipke; Zheng Wang; Joonyoung Kim; Timothy J. McCarthy; Paul M. Allen

doi:10.1038/ni775

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

Brian T. Wipke, Zheng Wang, Joonyoung Kim, Timothy J. McCarthy, Paul M. Allen

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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.

Original language	English
Pages (from-to)	366-372
Number of pages	7
Journal	Nature immunology
Volume	3
Issue number	4
DOIs	https://doi.org/10.1038/ni775
State	Published - 2002

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@article{b53fa24a36164735ae3627992506d50f,

title = "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 na{\"i}ve 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.",

author = "Wipke, {Brian T.} and Zheng Wang and Joonyoung Kim and McCarthy, {Timothy J.} and Allen, {Paul M.}",

note = "Funding Information: We thank T. Sharp, J. Engelbach, L. Jones and N. Mercer for assistance with animal handling in microPET and biodistribution studies; M.Welch and D. Reichert for support; R. Laforest for help in data analysis and software engineering; D. Kreamalmeyer for serum banking and managing the mouse colony; E. Unanue and H.W.Virgin IV for reading the manuscript; L. Mandik-Nayak, E. Hailman, L. Norian and F. Shih for comments and discussion; and J. Smith for administrative assistance.This work was supported by the NIH (WU Small Animal Imaging Resource R24CA083060,WU Research Resource In Radionuclide Research R24CA086307 and P01AI31238).",

year = "2002",

doi = "10.1038/ni775",

language = "English",

volume = "3",

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AU - Wipke, Brian T.

AU - Wang, Zheng

AU - Kim, Joonyoung

AU - McCarthy, Timothy J.

AU - Allen, Paul M.

N1 - Funding Information: We thank T. Sharp, J. Engelbach, L. Jones and N. Mercer for assistance with animal handling in microPET and biodistribution studies; M.Welch and D. Reichert for support; R. Laforest for help in data analysis and software engineering; D. Kreamalmeyer for serum banking and managing the mouse colony; E. Unanue and H.W.Virgin IV for reading the manuscript; L. Mandik-Nayak, E. Hailman, L. Norian and F. Shih for comments and discussion; and J. Smith for administrative assistance.This work was supported by the NIH (WU Small Animal Imaging Resource R24CA083060,WU Research Resource In Radionuclide Research R24CA086307 and P01AI31238).

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

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JO - Nature immunology

JF - Nature immunology

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

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