Patients can be immune-compromised for as long as a year, making them vulnerable to pathogens that most people would fight off easily.
One such pathogen is cytomegalovirus (CMV), a member of the herpes virus family. People usually get CMV early in life (from childhood to early adulthood), experience mild symptoms and move on. However, for immune-compromised patients, CMV can be a serious and deadly complication.
While treating bone marrow transplant patients, Dr. Jaime Green, an Infectious Disease fellow at UC San Diego, became concerned that many were developing infections with CMV. She began researching this condition and realized she needed to learn more about specific immune system pathways to better understand what was happening to her patients. This led her to Sanford-Burnham’s Dr. Carl Ware.
“I started to get interested more in the immune system and what the T-cell responses were doing,” says Dr. Green. “I connected with Dr. Ware since he is an immunologist who specializes in herpes infections, and we came up with some interesting projects.”
Specifically, Dr. Green is interested in Dr. Ware’s research in type 1 interferons and how they link the innate and adaptive immune response—a link that is essential to control CMV.
“So we’re interested in identifying whether these type 1 interferon signatures are different in these patients,” says Dr. Green. “If the patient has an intact interferon signature pathway, are they less susceptible to getting the CMV infection, and would we treat these patients differently than the patients who do not have an interferon signature yet? So we’re looking for biomarkers in the short term and possible novel therapeutics in the long term.”
The quest for biomarkers is critical. The treatment for CMV is ganciclovir, which can be given preventively to all patients or only to those with active CMV. Unfortunately, ganciclovir increases the risk of bacterial infection and can endanger the bone marrow graft. Finding biomarkers could help physicians choose which patients should receive ganciclovir and when.
“We take weekly blood samples from these patients for the first three months after transplant, and then we draw a blood sample monthly up until the first year, and follow these patients clinically to determine who gets CMV infections and who has normal engraftment versus difficulties in engraftment,” says Dr. Green. All of these samples will be run to look at their interferon signatures in the lab at Sanford-Burnham.
This research could be a great benefit for patients. When Dr. Green looked at stem cell transplant recipients at UCSD, she found that 40 percent of patients in the past five years had CMV infection.
