4(th) Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece.
2(nd) Department of Critical Care Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Cell Rep Med. 2022 Nov 15;3(11):100817. doi: 10.1016/j.xcrm.2022.100817.
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.
免疫激活状态可能指导脓毒症的靶向免疫治疗。在一项双盲、双模拟随机临床试验中，240 例因肺部感染、菌血症或急性胆管炎导致的脓毒症患者接受了血清铁蛋白和 HLA-DR/CD14 的测量。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>4420ng/mL 和<5000 HLA-DR 受体/单核细胞作为生物标志物，将患者分为 MALS（20.0%）、免疫麻痹（42.9%）和中间状态（37.1%）。死亡率分别为 79.1%、66.9%和 41.6%。免疫治疗组中 42.9%的患者在 SOFA 评分下降 7 天后存活，而安慰剂组中只有 10.0%的患者存活（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治疗的分层。Clinicaltrials.gov 注册号：NCT03332225。
