An international team of researchers at the University of California, San Francisco (UCSF), in the United States and Saint-Louis Hospital in Paris, France have found that a virus hiding in the gut may trigger the onset of a severe complication known as graft-versus-host disease (GvHD) in patients who receive bone marrow transplants. The new study published online in Nature Medicine, unveils a viral biomarker that could allow clinicians to assess patients’ risk of an acute form of the disease known as enteric GvHD, which affects the gastrointestinal system.
The team used a technique known as metagenomic next-generation sequencing (mNGS) to catalog microbes in patients’ digestive tracts by rapidly and concurrently sequencing genetic material of all organisms, thus monitoring the evolving bacterial population, known as microbiome, and viral population, known as virome, throughout the transplantation process.
The researchers scanned stool samples taken from 44 patients before they received a transplant and up to six weeks after, and sequenced all the deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in the samples. They identified a number of viruses that flared up in the guts of patients who developed the deadly condition. Of particular note were members of the picobirnavirus (PBV) family.
PBVs are a family of viruses more diverse than the human immunodeficiency virus (HIV). In fact, each of the 18 patients who tested positive for PBV was carrying a different strain, a diversity that makes it challenging to detect PBVs using a simple lab test. And the presence of these viruses before transplantation, even in very small populations, was a reliable sign that a patient would likely develop the disease after a transplant.
In addition, the team observed a previously unreported “bloom” of other resident viruses that occurred three to five weeks after patients had received transplants. The onset of GvHD appeared to trigger the late awakening of these covert viruses, laying to rest a longstanding chicken-and-egg debate: which comes first, viral infection or GvHD? The researchers concluded that much of the viral flare is due to reactivation of latent gut infections following transplantation.
Charles Chiu, an associate professor of laboratory medicine at UCSF and principal investigator of the study, and his colleagues now hope to develop a metagenomics-based test to screen patients before transplantation, so as to explore the potential utility of PBV as a predictive biomarker.
GvHD affects up to 60 percent of patients who undergo bone marrow stem-cell transplants, and kills about half of those affected. GvHD is a mirror image of organ rejection, in which immune cells in the transplant attack its new host, the patient.
Bone Marrow Transplant
A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside your bones. The bone marrow produces blood cells. Stem cells are immature cells in the bone marrow that give rise to all of your different blood cells. This procedure is effective for treatment of aplastic anemia, leukemia and other blood related diseases.