Editors' ChoiceOrgan Transplantation

Imaging the Host Immune Response

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Science Translational Medicine  14 Jul 2010:
Vol. 2, Issue 40, pp. 40ec113
DOI: 10.1126/scitranslmed.3001469

In organ transplantation, the ability to monitor the host’s immune response to a graft is essential for the clinician to tailor immunosuppressive therapy. Currently, heart transplant recipients routinely undergo serial invasive biopsies, which increase the risk of complications such as bleeding, infection, arrhythmias, and puncture of the heart, lung, or major blood vessels. Now, Swirski et al. introduce a noninvasive technique of monitoring organ rejection by imaging a specific subset of tissue-infiltrating leukocytes.

The researchers first studied the leukocyte populations migrating to the graft after heart transplantation in a mouse model. They found that a subset of monocytes, which express high levels of Ly-6C (Ly-6Chi) on their cell surfaces, promote inflammation and accumulate in rejected allografts—the hearts from immunologically mismatched donors. On the basis of their previous work, during which they profiled genes expressed by leukocytes, the researchers identified myeloperoxidase (MPO) as an enzyme uniquely expressed by the Ly-6Chi monocyte subset. Magnetic resonance imaging of MPO activity with an MPO-activated contrast dye in mouse heart transplant recipients specifically generated a signal in rejected allografts, but not in immunosuppressed or MPO-deficient allograft recipients. To assess the translational potential of this approach, Swirski et al. further analyzed biopsy samples from human heart transplant recipients. Clinical samples with severe rejection showed increased numbers of MPO-expressing cells, suggesting that the detection of MPO can be used as a noninvasive means of monitoring heart allograft rejection.

MPO imaging has the potential to allow for frequent monitoring of heart allograft status, without generating the risks and anxiety associated with an invasive needle biopsy. However, MPO-expressing cells also play a role in diseases such as ischemia (a restriction in blood supply); thus, signal enhancement may be seen in patients with progressive coronary artery disease. Although the accuracy of this new approach has yet to be demonstrated in the clinical setting, MPO detection holds promise as an alternative tool to monitor the status of transplanted organs.

F. K. Swirski et al., Myeloperoxidase-rich Ly-6C+ myeloid cells infiltrate allografts and contribute to an imaging signature of organ rejection in mice. J. Clin. Invest. 120, 2627–2634 (2010). [Full Text]

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