Protein related to graft-versus-host disease identified

A protein present in immune cells may enable early diagnosis and treatment of complications in blood stem cell transplant recipients, according to research from the University of Birmingham.

After receiving a blood stem cell transplant, almost one in two transplant recipients experience either mild or severe 'graft-versus-host disease' (GVHD), a condition in which the donor's T-cells (a type of immune cell) react against the patient's organs. In the new study, researchers have identified that a protein called CD70 is highly present in the surface of T-cells extracted from the blood of patients experiencing GVHD.

Dr Kriti Verma, first author of the study and postdoctoral researcher at the University of Birmingham, said: 'T-cells are key players in the body's immune response, and CD70 shows up on them when they're highly active – especially when they're responding aggressively to what they see as foreign, such as the patient's own cells in GVHD'.

Around 1000 people a year receive an allogeneic hematopoietic stem cell transplant. This treatment uses healthy cells from a donor to replace the damaged blood and immune cells of patients with blood cancers or other bone marrow failure diseases. In acute cases of GVHD, patients receiving stem cell transplants usually develop symptoms, such as skin rashes or nausea, within the first 100 days. These symptoms are consequences of T-cells, which develop from the donor's stem cells, not recognising the recipient's body – thereby becoming 'activated' and mounting an immune response.

The authors of this study published in Blood Advances focused on the T-cell surface protein CD70 to see if this marker could help identifying people who would develop GVHD. The team found that levels of CD70 were 30 to 50 times higher on T-cells within the first two weeks after transplant.

The CD70-expressing T-cells were present in biopsies from patients with GVHD. These T-cells expressed genes linked with the use of energy and quick proliferation, two factors associated with the inflammatory responses that drive GVHD. The authors also found that these T-cells produced higher levels of inflammatory molecules called cytokines.

When CD70 is expressed, it interacts with its receptor CD27, driving T-cell activation. When the researchers blocked this interaction using antibodies against CD27, markers of T-cell activation decreased. CD27 shreds a fragment when interacts with CD70. The researchers found this fragment, sCD27, was elevated in the blood of people that developed graft disease compared to those who did not.

'This suggests that interrupting this CD70-CD27 signal could be a new way to treat or even prevent GVHD by calming down the overactive immune response,' Dr Verma said. 'Because CD27 is cleaved and found in the blood we think we could measure it and use it as early diagnostic marker for GVHD in a blood test.'