Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial

被引：76

作者：

Leventogiannis, Konstantinos ^{[1
]}

Kyriazopoulou, Evdoxia ^{[1
]}

Antonakos, Nikolaos ^{[1
]}

Kotsaki, Antigone ^{[1
]}

Tsangaris, Iraklis ^{[2
]}

Markopoulou, Dimitra ^{[3
]}

Grondman, Inge ^{[4
,5
]}

Rovina, Nikoleta ^{[6
]}

Theodorou, Vassiliki ^{[7
]}

Antoniadou, Eleni ^{[8
]}

Koutsodimitropoulos, Ioannis ^{[9
]}

Dalekos, George ^{[10
]}

Vlachogianni, Glykeria ^{[11
]}

Akinosoglou, Karolina ^{[12
]}

Koulouras, Vassileios ^{[13
]}

Komnos, Apostolos ^{[14
]}

Kontopoulou, Theano ^{[15
]}

Prekates, Athanassios ^{[16
]}

Koutsoukou, Antonia ^{[6
]}

van der Meer, Jos W. M. ^{[4
,5
]}

Dimopoulos, George ^{[6
]}

Kyprianou, Miltiades ^{[1
]}

Netea, Mihai G. ^{[4
,5
]}

Giamarellos-Bourboulis, Evangelos J. ^{[1
]}

机构：

[1] Natl & Kapodistrian Univ Athens, Dept Internal Med 4, Med Sch, Athens, Greece

[2] Natl & Kapodistrian Univ Athens, Med Sch, Dept Crit Care Med 2, Athens, Greece

[3] KAT Kifisia Gen Hosp, Intens Care Unit, Kifisia, Greece

[4] Radboud Univ Nijmegen Med Ctr, Dept Internal Med, Nijmegen, Netherlands

[5] Radboud Univ Nijmegen Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands

[6] Natl & Kapodistrian Univ Athens, Dept Pulm Med 1, Athens, Greece

[7] Univ Thrace, Dept Crit Care Med, Alexandroupolis, Greece

[8] G GennimatasThessaloniki Gen Hosp, Intens Care Unit, Thessaloniki, Greece

[9] Latse Elefsis Gen Hosp, Intens Care Unit, Athens, Greece

[10] Gen Univ Hosp Larissa, Natl Expertise Ctr Greece Autoimmune Liver Dis, Dept Med & Res Lab Internal Med, European Reference Network Hepatol Disases ERN RAR, Larisa 41110, Greece

[11] Aghios DimitriosThessaloniki Gen Hosp, Intens Care Unit, Thessaloniki, Greece

[12] Patras Univ Hosp, Dept Internal Med, Patras, Greece

[13] Univ Ioannina, Dept Crit Care Med, Ioannina, Greece

[14] Larissa Gen Hosp, Intens Care Unit, Larisa, Greece

[15] Evangelismos Athens Gen Hosp, Dept Internal Med 5, Athens, Greece

[16] Tzane Piraeus Gen Hosp, Intens Care Unit, Piraeus, Greece

来源：

CELL REPORTS MEDICINE | 2022年 / 3卷 / 11期

关键词：

ANTIGEN-DR EXPRESSION; DOUBLE-BLIND; PHASE-III; DEFINITIONS; MULTICENTER; MORTALITY; FEATURES;

D O I：

10.1016/j.xcrm.2022.100817

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 syn-drome (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.

引用

页数：14

共 20 条

[1] Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases [J].

Agache, Ioana ;

Akdis, Cezmi A. .

JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (04) :1493-1503

[2] Identification of Biomarkers of Response to IFNg during Endotoxin Tolerance: Application to Septic Shock [J].

Allantaz-Frager, Florence ;

Turrel-Davin, Fanny ;

Venet, Fabienne ;

Monnin, Cecile ;

Saint Jean, Amelie De ;

Barbalat, Veronique ;

Cerrato, Elisabeth ;

Pachot, Alexandre ;

Lepape, Alain ;

Monneret, Guillaume .

PLOS ONE, 2013, 8 (07)

[3] The international sepsis forum consensus conference on definitions of infection in the intensive care unit [J].

Calandra, T ;

Cohen, J .

CRITICAL CARE MEDICINE, 2005, 33 (07) :1538-1548

[4] Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study [J].

Davenport, Emma E. ;

Burnham, Katie L. ;

Radhakrishnan, Jayachandran ;

Humburg, Peter ;

Hutton, Paula ;

Mills, Tara C. ;

Rautanen, Anna ;

Gordon, Anthony C. ;

Garrard, Christopher ;

Hill, Adrian V. S. ;

Hinds, Charles J. ;

Knight, Julian C. .

LANCET RESPIRATORY MEDICINE, 2016, 4 (04) :259-271

[5] Monitoring of circulating monocyte HLA-DR expression in a large cohort of intensive care patients: relation with secondary infections [J].

de Roquetaillade, C. ;

Dupuis, C. ;

Faivre, V ;

Lukaszewicz, A. C. ;

Brumpt, C. ;

Payen, D. .

ANNALS OF INTENSIVE CARE, 2022, 12 (01)

[6] Monocyte deactivation in septic patients: Restoration by IFN-gamma treatment [J].

Docke, WD ;

Randow, F ;

Syrbe, U ;

Krausch, D ;

Asadullah, K ;

Reinke, P ;

VolK, HD ;

Kox, W .

NATURE MEDICINE, 1997, 3 (06) :678-681

[7] Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome [J].

Fardet, Laurence ;

Galicier, Lionel ;

Lambotte, Olivier ;

Marzac, Christophe ;

Aumont, Cedric ;

Chahwan, Doumit ;

Coppo, Paul ;

Hejblum, Gilles .

ARTHRITIS & RHEUMATOLOGY, 2014, 66 (09) :2613-2620

[8] Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach [J].

Hotchkiss, Richard S. ;

Monneret, Guillaume ;

Payen, Didier .

LANCET INFECTIOUS DISEASES, 2013, 13 (03) :260-268

[9] Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis [J].

Kyriazopoulou, Evdoxia ;

Leventogiannis, Konstantinos ;

Norrby-Teglund, Anna ;

Dimopoulos, Georgios ;

Pantazi, Aikaterini ;

Orfanos, Stylianos E. ;

Rovina, Nikoletta ;

Tsangaris, Iraklis ;

Gkavogianni, Theologia ;

Botsa, Elektra ;

Chassiou, Eleftheria ;

Kotanidou, Anastasia ;

Kontouli, Christina ;

Chaloulis, Panagiotis ;

Velissaris, Dimitrios ;

Savva, Athina ;

Cullberg, Jonas-Sunden ;

Akinosoglou, Karolina ;

Gogos, Charalambos ;

Armaganidis, Apostolos ;

Giamarellos-Bourboulis, Evangelos J. .

BMC MEDICINE, 2017, 15

[10] Reversal of Immunoparalysis in Humans In Vivo A Double-Blind, Placebo-controlled, Randomized Pilot Study [J].

Leentjens, Jenneke ;

Kox, Matthijs ;

Koch, Rebecca M. ;

Preijers, Frank ;

Joosten, Leo A. B. ;

van der Hoeven, Johannes G. ;

Netea, Mihai G. ;

Pickkers, Peter .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2012, 186 (09) :838-845

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