Researchers have mapped how the immune response in people with sepsis changes over time.\u00a0<\/p>\n
Sepsis is a life-threatening condition that occurs when there is misfiring of the immune response to infection. In sepsis, there is failure of the vital organs, and it can be fatal even when treated quickly. It\u2019s estimated that there are over 160 million cases and about 21 million deaths from sepsis worldwide each year.<\/p>\n
Current treatments for sepsis focus on treating the underlying infection with antimicrobials and providing supportive care for failing vital organs. Despite efforts to treat the misfiring immune system, none have been successful at achieving improved outcomes for patients.<\/p>\n
In the new study, published today in Immunity, researchers sought a more detailed understanding of the immune response mechanisms that change over time in patients with sepsis.<\/p>\n
They analyzed blood samples collected at four different timepoints (between admission\u00a0to and discharge from\u00a0critical care) from\u00a0critically ill\u00a0patients with sepsis at Guy’s and St\u00a0Thomas’\u00a0NHS Foundation Trust.\u00a0To build a detailed picture of the immune response,\u00a0called an ‘immune profile,’\u00a0the researchers\u00a0looked at multiple layers of\u00a0immune response\u00a0information in the blood samples,\u00a0including data\u00a0on immune\u00a0cells, gene expression and protein expression analyses\u00a0that are changing.\u00a0<\/p>\n
Using machine learning approaches,\u00a0they then combined these layers of information to generate a more comprehensive immune profile for the first time in patients with sepsis.\u00a0<\/p>\n
The analyses revealed an immune trajectory that had three distinct, temporal immune states (referred to as STImS) between admission and recovery, with each state involving different immune cell activity, and immune response programmes.\u00a0<\/p>\n
Importantly, these\u00a0sepsis\u00a0immune states didn’t match\u00a0to\u00a0the clinical\u00a0stage of sepsis.\u00a0For example,\u00a0the\u00a0‘early’ immune state (STImS1) was not the same as\u00a0the\u00a0early\u00a0clinical stage of sepsis, which is often the day a clinician diagnoses sepsis.\u00a0<\/p>\n
The researchers say these findings could have important implications when considering how best to treat sepsis patients\u00a0\u2013\u00a0specifically with what treatments and when.\u00a0<\/p>\n
The research was carried out by Dr Matthew Fish during his PhD at King’s College London in the laboratory of Professor Manu Shankar-Hari. His work was supported by a National Institute of Academic Anesthesia BJA\/RCoA fellowship. Dr Fish is now a postdoctoral researcher at Massachusetts General Hospital where he continues to study sepsis and the immune system.\u00a0<\/p>\n
The study\u00a0also\u00a0brought together researchers from King’s College London, including\u00a0Dr\u00a0Chad Swanson, Reader\u00a0in\u00a0the School of Immunology & Microbial Sciences, and\u00a0Professor\u00a0Mervyn Singer, Professor of\u00a0Intensive Care Medicine\u00a0at\u00a0University College London.\u00a0<\/p>\n
The main aim of this work was to build a\u00a0profile of\u00a0sepsis immune responses\u00a0over time.\u00a0When people are admitted to hospital with sepsis, they are usually classed as having ‘early’ sepsis \u2013 but\u00a0our findings\u00a0show that\u00a0this isn’t necessarily the case\u00a0\u2013 their immune system may already be at\u00a0stages of the immune response.\u00a0Knowing exactly what is happening to a patient’s immune system\u00a0during sepsis\u00a0could\u00a0identify\u00a0which treatments are likely to work\u00a0best.”\u00a0<\/p>\n
Dr. Matthew Fish, former PhD student at King’s College London and lead author of the paper<\/p>\n
Professor Manu Shankar-Hari, Professor of Critical Care Medicine at King’s College London, Honorary Consultant at Guy’s and St\u00a0Thomas’\u00a0NHS Foundation Trust\u00a0and senior author of the paper, said:\u00a0“This research shows\u00a0the\u00a0importance of\u00a0looking\u00a0at the\u00a0changing\u00a0architecture of the immune system in sepsis\u00a0over\u00a0time, rather than just taking a snapshot view.\u00a0We need to find\u00a0better\u00a0ways\u00a0to\u00a0treat the misfiring immune system.\u00a0Only by understanding\u00a0the\u00a0intricacies\u00a0of the immune system\u00a0in all its component parts\u00a0–\u00a0by integrating and dynamically mapping cell and molecular\u00a0immunobiology to determine\u00a0why\u00a0the\u00a0very system designed to\u00a0protect\u00a0us from\u00a0infections\u00a0is\u00a0misfiring\u00a0in sepsis\u00a0–\u00a0can\u00a0we\u00a0begin to improve outcomes for patients\u00a0by treating the misfiring immune system.”\u00a0<\/p>\n
The authors say the next step for this work is to\u00a0understand what\u00a0causes changes in the immune system between\u00a0onset of\u00a0infection\u00a0to\u00a0the development of sepsis. Understanding these changes\u00a0could help identify\u00a0new treatment targets\u00a0and approaches to\u00a0reduce\u00a0either\u00a0the progression\u00a0to sepsis\u00a0or the severity of sepsis, with the potential to improve outcomes and make a difference to lives of\u00a0millions\u00a0affected by serious infections worldwide.<\/p>\n
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