November 21, 2013 | Stephen Quake has been on a roll finding innovative uses for cell-free DNA: it was his Stanford lab that pioneered the screening of this freely circulating DNA for chromosomal abnormalities, technology that now forms the basis of Verinata Health's non-invasive prenatal test for aneuploid conditions like Down syndrome. Now his lab is suggesting another potential clinical use for cell-free DNA, to estimate patients' chances of suffering organ rejection after a transplant. The suggestion is based on a recent study, published today in Cell, that followed 96 patients for two years after heart and lung transplants, taking blood samples at regular intervals and extracting and sequencing cell-free DNA. Quake's team was not looking at the patients' DNA, but at their microbiomes, the microorganisms moving through the bloodstream. Since transplant patients are kept on long-term immunosuppressants, it seemed likely that their microbiomes would change under their drug regimens as their immune systems became less sensitive to foreign bodies.

One freeloader, the mysterious anellovirus, stood out as a consistent indicator of immune surveillance. Since their discovery in the late 1990s, the Anelloviridae family has proven to be an extremely common and diverse group of viruses regularly found in humans and other species. Despite chronic infections being commonplace, anellovirus does not appear to be a disease-causing agent. In this study, Quake's lab found that this virus' ubiquity may be a boon to clinicians, as the volume of anellovirus DNA in cell-free genetic samples tracked closely and reliably with the suppression of the immune system. More notably, all twenty subjects who experienced organ rejection in the two years following transplant displayed significantly lower levels of anellovirus throughout the duration of the study. This finding, if borne out in more targeted research, could eventually pave the way for non-invasive screens using anellovirus DNA as a proxy to measure patients' levels of immunosuppression, and thus their risks of suffering organ rejection. Such a test would give physicians the information they need to recommend more or less aggressive courses of immunosuppressants before symptoms of organ rejection appear.