Novel Biomarker to Detect CMV T Cell Immunity
University of Pittsburgh researchers have developed an assay to predict cytomegalovirus (CMV) T cell immunity. This assay uses killer cell lectin-like receptor subfamily G member 1 (KLRG1) expression to assess T cell function and predict the risk of virus control. Clinical application would enable clinicians to identify patients most at risk from a CMV infection, effectively personalizing the anti-viral treatment administered.
Description
CMV, an opportunistic pathogen, is generally harmless to most people. However, it can cause severe complications, including death, in immunocompromised patients. A particular risk group are solid organ transplant recipients (SOTRs). It is vital for clinicians to assess the risk, particularly in lung transplant recipients (LTRs) who were previously seronegative for CMV but receive allografts from CMV seropositive donor (D+R-), to instigate early treatment and minimize the risk of death. Failure to manage CMV in LTRs can result in complications including chronic lung allograft dysfunction and bronchiolitis obliterans syndrome impacting long-term survival and quality of life. The development of assays to predict risk would arm clinicians with the tools necessary to selectively target patients requiring antiviral prophylaxis to improve survival rates among LTRs.Applications
Indications- Lung transplant recipients
- Immunocompromised patients
Advantages
While antiviral prophylaxis strategies can reduce the risk of CMV infection and associated consequences in D+R- LTRs, this treatment can be costly and lead to adverse effects. Identifying patients most likely to benefit from treatment would be economically beneficial while also reducing the risks of adverse effects from unnecessary treatment of lower-risk patients.Previous research has demonstrated CMV-specific T cell immunity is driven by the key Type-1 immunity transcriptional regulator, T-bet. T cell immunity can predict how any high-risk LTRs might control a CMV infection. It has now been discovered that KLRG1+ expression levels in CD8+ T cells strongly correlate to the patient’s ability to control a CMV infection and KLRG1 expression can be viewed as an immune surrogate for T-bet. KLRG1 surface expression can be studied more rapidly than other more complex functional immunity assays. This novel assay is the first to use KLRG1 expression and could allow clinicians to predict the risk of CMV to LTRs and begin treatment in the most at-risk patients.