| Author |
Bhan, Atul Ehrlich, Hartmut Terhorst, Cox Tam, Frederick W. K. Mudde, Geert C. Scheiflinger, Friedrich Jilma, Bernd Bhangal, Gurjeet Douillard, Patrice Tilg, Herbert Rieger, Manfred Völkel, Dirk Thiele, Michael Yu, Mei-Ching Kerschbaumer, Randolf J. Schinagl, Alexander Kühnel, Harald Pusey, Charles D. Smith, Jennifer Moschen, Alexander McDaid, John P. Magelky, Erica Kovarik, Josef Cook, H. Terence |
| Description |
Author Affiliation: Thiele M ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Kerschbaumer RJ ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Tam FW ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); Völkel D ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Douillard P ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Schinagl A ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Kühnel H ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Smith J ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); McDaid JP ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); Bhangal G ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); Yu MC ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); Pusey CD ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); Cook HT ( Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W12 0NN, United Kingdom); Kovarik J ( Department of Nephrology, Wilhelminenspital, 1160 Vienna, Austria); Magelky E ( Department of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215); Bhan A ( Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02214); Rieger M ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Mudde GC ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Ehrlich H ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria); Jilma B ( Department of Clinical Pharmacology, Medical University Vienna, 1090 Vienna, Austria); Tilg H ( Department of Internal Medicine I, Endocrinology, Gastroenterology & Metabolism, Medical University Innsbruck, 6020 Innsbruck, Austria.); Moschen A ( Department of Internal Medicine I, Endocrinology, Gastroenterology & Metabolism, Medical University Innsbruck, 6020 Innsbruck, Austria.); Terhorst C ( Department of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215); Scheiflinger F ( Baxter Biomedical Research Center, Baxter Innovations GmbH, 2304 Orth/Donau, Austria) |
| Abstract |
Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, is a potential therapeutic target. MIF is markedly different from other cytokines because it is constitutively expressed, stored in the cytoplasm, and present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention is challenging because of the need to neutralize a ubiquitous protein. In this article, we report that MIF occurs in two redox-dependent conformational isoforms. We show that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF is selectively expressed in the plasma and on the cell surface of immune cells of patients with different inflammatory diseases. In patients with acute infections or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups. In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute and chronic enterocolitis and improved, in synergy with glucocorticoids, renal function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF represents the disease-related isoform of MIF; oxMIF is therefore a new diagnostic marker for inflammation and a relevant target for anti-inflammatory therapy. |
