Abstract：
The state of immune activation may guide targeted immunotherapy in sepsis. In a double-blind, double-dummy randomized clinical study, 240 patients with sepsis due to lung infection, bacteremia, or acute cholangitis were subjected to measurements of serum ferritin and HLA-DR/CD14. Patients with macrophage activation-like syndrome (MALS) or immunoparalysis were randomized to treatment with anakinra or recombinant interferon-gamma or placebo. Twenty-eight-day mortality was the primary endpoint; sepsis immune classification was the secondary endpoint. Using ferritin >4,420 ng/mL and <5,000 HLA-DR receptors/monocytes as biomarkers, patients were classified into MALS (20.0%), immunoparalysis (42.9%), and intermediate (37.1%). Mortality was 79.1%, 66.9%, and 41.6%, respectively. Survival after 7 days with SOFA score decrease was achieved in 42.9% of patients of the immunotherapy arm and 10.0% of the placebo arm (p = 0.042). Three independent immune classification strata are recognized in sepsis. MALS and immunoparalysis are proposed as stratification for personalized adjuvant immunotherapy. Clinicaltrials.gov registration NCT03332225.
摘要：
免疫激活状态可指导脓毒症的靶向免疫治疗。在双盲中，双模拟随机临床研究，240例因肺部感染引起的脓毒症患者，菌血症,或急性胆管炎接受血清铁蛋白和HLA-DR/CD14的测量。患有巨噬细胞活化样综合征（MALS）或免疫麻痹的患者被随机分配接受anakinra或重组干扰素-γ或安慰剂治疗。28天死亡率是主要终点；脓毒症免疫分类是次要终点。使用铁蛋白>4,420ng/mL和<5,000个HLA-DR受体/单核细胞作为生物标志物，患者分为MALS（20.0%），免疫麻痹（42.9%），和中级（37.1%）。死亡率为79.1%，66.9%,和41.6%，分别。免疫疗法组42.9%的患者和安慰剂组10.0%的患者在SOFA评分降低的7天后生存(p=0.042)。在脓毒症中识别出三个独立的免疫分类层。MALS和免疫麻痹被提议作为个性化辅助免疫疗法的分层。Clinicaltrials.gov注册NCT03332225.
