However, if a patient’s immune system is out of balance, these treatments can backfire. Sepsis, for instance, can stem from viral or bacterial infections, but the symptoms are similar. Bacterial sepsis worsens by the hour and requires a swift prescription of antibiotics — that’s why doctors often immediately administer antibiotics. But it’s not without risk, according to Khatri. If the infection turns out to be viral, the antibiotics are not only ineffective; they can create ideal conditions for antibiotic-resistant bacteria to flourish.
Khatri found that categorizing patients into groups that signify whether and how different arms of their immune system are functioning — or not functioning — can help doctors make better, faster, targeted treatment decisions. For example, if a patient has myeloid dysregulation, they will likely benefit from drugs that target the myeloid immune response, while patients with lymphoid dysregulation need drugs focused on the lymphoid immune response. If both are dysregulated, doctors may choose a combination of lymphoid- and myeloid-targeting drugs. This information can be used to prescribe the proper treatment once, at the beginning, eliminating any guesswork.
Further data analysis also showed that patients with high lymphoid dysregulation, whether they had sepsis or were suffering from burns, generally benefited from steroid treatments; mortality rates improved when appropriately treated. In contrast, when both myeloid and lymphoid immune responses were balanced, patients did not benefit from steroid treatment, and mortality rates worsened. Prospective clinical studies are needed to identify more specific treatments, such as steroids, Khatri said.
Dysregulation beyond the ICU
Khatri and his team plan to pair the HI-DEF scores with the TriVerity diagnostic test to create a one-stop shop that can help doctors analyze blood samples, identify immune system dysregulation and guide treatments in as little as 30 minutes. In the future, Khatri hopes, doctors could take a patient’s blood sample, run it through the tool and receive a gene signature analysis that tells them the patient’s diagnosis as well as whether and how they should be treated.
“You could have a platform to identify the infection, severity of the illness and the treatment quickly,” Khatri said.
Khatri also hopes the dysregulation scoring system will one day move beyond critical illnesses. Signs of immune dysregulation can appear long before a patient ends up in the ICU, so the tool could be used to surveil general health concerns, he said. (Previous work conducted by Khatri found that patients with other high-risk health concerns, such as diabetes, had a higher number of “bad” gene signatures.) More research is needed to determine whether lifestyle changes could alter these signatures, but it’s a signal to Khatri that there’s a strong association warranting more exploration.
“My vision is to make an immune dysregulation assessment part of your annual health checkup,” he said.
Researchers at Inflammatix, Inc.; the University of Amsterdam; the University of Groningen; the University of Malta; the National and Kapodistrian University of Athens; the Hellenic Institute for the Study of Sepsis; St. James’s Hospital in Dublin; the University of Barcelona; Johns Hopkins University; Emory University; the University of Cincinnati; the University of Florida College of Medicine; Charles University in the Czech Republic; the University of Pennsylvania; the University of Southern California; the Medical College of Wisconsin; the University of Florida College of Medicine–Jacksonville; Washington University in St. Louis; the University of Kentucky; Henry Ford Hospital; Hackensack Meridian Health; Cleveland Clinic; the University of California, Davis; Texas Tech University; the University of South Alabama; Vanderbilt University; the University of Massachusetts; the University of Iowa; the University of Pittsburgh; Geisinger Commonwealth School of Medicine; and Beth Israel Deaconess Medical Center contributed to the research.
Funding for the research came from the Stanford Training Program in Lung Biology, the National Institutes of Health (grants R35GM155165, R21GM150093, R21GM151703, R01HL152083, U19AI167903 and 2U19AI057229-21) and Inflammatix, Inc.