Key Cell Type to Prevent Marrow Transplant Complication

A research team from the University of Wisconsin–Madison recently identified a key cell population that causes graft-versus-host disease (GVHD), a life-threatening complication after receiving a bone marrow transplant. 

This group of cells was revealed in the journal Science Advances on March 24, as a potential target to make bone marrow transplants safer and more effective.  

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The Mechanism of Action of GVHD

An allogeneic bone marrow transplant, which means receiving a foreign organ or tissue from a donor, is a common therapy for blood cancers and other immune system diseases. The patient’s defective immune cells would be replaced with the donor’s healthy cells. Despite its therapeutic effect, they can also cause GVHD, a detrimental side effect in which donor T cells could attack the patient’s healthy cells and cause symptoms similar to autoimmune disease.

This situation could happen due to the antigen-specific responses of immune cells, which can differentiate between “self” or “non-self” cells to protect our body from infections. The recognizing ability depends on histocompatibility genes that provide instructions for making a group of related proteins known as major histocompatibility complex (MHC proteins) or human leukocyte antigens (HLA). 

Donors’ immune cells will recognize the MHC proteins of the recipient tissue as foreign cells thus activating an immune response to kill the intruders. The proliferation of donors’ cytotoxic CD8+ T cells will subsequently cause severe organ damage. 

A Potential Biomarker to Predict GVHD Development

From an observational clinical study that includes 400 clinical samples from 35 adult allogeneic hematopoietic cell transplantation recipients, the scientists identified a CD4+/CD8+ double-positive T cell (DPT) population, not present in starting grafts, whose presence was predictive of grade 2 GVHD or in more severe cases.

Based on the discovery, the team is optimistic to merge the biomarkers into a machine-learning algorithm that can output a risk prediction model. Thus, the clinicians could then use this model to understand a patient’s risk of relapse and developing more lethal GVHD.

Moreover, a targeted depletion strategy will be the final goal to act as a prophylaxis to treat the patients before they have all the detrimental effects of this disease.

What’s more, several studies uncovering the association of DPTs with other human chronic inflammatory disorders, including rheumatoid arthritis, hepatitis B and C, β-thalassemia, and even cancers, making DPT a more valuable biomarker to be used in the clinical stage.

Author

Nai Ye Yeat