Kompoti Maria, Michopoulos Alexandros, Michalia Martha, Clouva-Molyvdas Phyllis-Maria, Germenis Anastasios E, Speletas Matthaios
Intensive Care Unit, Thriassion General Hospital of Eleusis, Athens, Greece.
Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece.
Immunobiology. 2015 Mar;220(3):414-21. doi: 10.1016/j.imbio.2014.10.006. Epub 2014 Oct 18.
Sepsis and septic shock frequently cause the admission or complicate the clinical course of critically ill patients admitted in the intensive care units (ICU). Genetic variations disrupting the immune sensing of infectious organisms, could affect the ability of the immune system to respond to infection, and may influence both the genetic predisposition to infection and the diversity of the clinical presentation of sepsis. The aim of this study was to uncover possible associations between common functional immune gene polymorphisms (of both innate and adaptive immunity) and ICU-acquired sepsis and mortality. The TLR4-D299G (rs4986790), TLR4-T399I (rs4986791), C2-c.841_849+19del28 (rs9332736), TACI-C104R (rs34557412), BAFFR-P21R (rs77874543), and BAFFR-H159Y (rs61756766) polymorphisms were detected in a cohort of 215 critically ill patients, admitted in an 8-bed medical/surgical ICU. Interestingly, TLR4-D299G, TLR4-T399I and BAFFR-P21R carriage was associated with a lower risk of ICU-acquired sepsis. This association applied particularly in medical patients, while in trauma and surgical patients no significant associations were observed. Moreover, carriers of TACI-C104R displayed an undiagnosed mild to moderate hypogammaglobulinemia along with a significantly lower survival rate in the ICU, although lethal events were not attributed to sepsis. These findings further elucidate the role that host immune genetic variations may play in the susceptibility to ICU-acquired sepsis and ICU mortality.
脓毒症和脓毒性休克经常导致重症患者入住重症监护病房（ICU）或使他们的临床病程复杂化。破坏感染性生物体免疫感知的基因变异，可能会影响免疫系统对感染的反应能力，并可能影响感染的遗传易感性以及脓毒症临床表现的多样性。本研究的目的是揭示常见功能性免疫基因多态性（先天免疫和适应性免疫）与ICU获得性脓毒症及死亡率之间可能存在的关联。在一个拥有8张床位的内科/外科ICU收治的215例重症患者队列中，检测了TLR4-D299G（rs4986790）、TLR4-T399I（rs4986791）、C2-c.841_849+19del28（rs9332736）、TACI-C104R（rs34557412）、BAFFR-P21R（rs77874543）和BAFFR-H159Y（rs61756766）多态性。有趣的是，携带TLR4-D299G、TLR4-T399I和BAFFR-P21R与较低的ICU获得性脓毒症风险相关。这种关联尤其适用于内科患者，而在创伤和外科患者中未观察到显著关联。此外，TACI-C104R携带者表现出未被诊断出的轻度至中度低丙种球蛋白血症，以及在ICU中显著较低的生存率，尽管致命事件并非由脓毒症所致。这些发现进一步阐明了宿主免疫基因变异在ICU获得性脓毒症易感性和ICU死亡率中可能发挥的作用。
