Researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU ) have developed a promising approach for the treatment of graft-versus-host disease (GvHD), a dangerous complication following bone marrow transplants. This transplant is the only chance of a cure for many leukemia patients, but the disease can trigger life-threatening inflammation, particularly in the intestines. The new findings could provide the basis for a targeted therapy.

GvHD occurs when donated immune cells attack the recipient’s body. Macrophages in particular, so-called phagocytes, play a central role as they remove dead or inflammation-promoting cells. If these are not sufficiently broken down, excessive immune reactions occur. A research team led by Dr. Heiko Bruns at the Chair of Haematology and Internal Oncology at FAU, in collaboration with the Universities of Regensburg and Würzburg, has deciphered the mechanism behind this complication as part of the Collaborative Research Centre/Transregio 221.

The scientists discovered that the protein CD47 plays a key role. T cells that carry high levels of this protein on their surface send a signal to the macrophages that prevents them from eliminating the cells. T cells are essential for immune defense, but in GvHD they can trigger inflammation that damages the body. The researchers discovered that an antibody against CD47, which is already used therapeutically, removes this inhibition. This enabled the macrophages to eliminate the disease-causing T cells more effectively, which significantly alleviated the symptoms of GvHD.

The results provide a basis for new therapies that could improve the treatment of complications following bone marrow transplants. In the future, they could help to increase the safety and effectiveness of this life-saving measure for leukemia patients.

Original Paper:

Augmented CD47 expression impairs alloreactive T-cell clearance after allo-HCT | Blood | American Society of Hematology

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