Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies

Abstract

Preliminary studies suggest that a subgroup of septic patients with severe immune alterations is at high risk of death or nosocomial infection and therefore could benefit from adjunctive immune stimulating therapies. There is thus an urgent need for robust biomarkers usable in routine conditions evaluating rapidly evolving immune status in patients. Although functional testing remains a gold standard, its standardization remains challenging. Therefore, surrogate markers such as monocyte HLA-DR expression, are being developed. Such biomarkers of immune functionality will enable a novel approach in the design of clinical trials evaluating immunostimulating therapies in sepsis at the right time and in the right patient.

Figure 1. T Lymphocyte alterations in sepsis and link with outcomes

TCR: T Cell Receptor, Ag: Antigen, MHC II: Major Histocompatibility Complex Class II, PD-1: Programmed cell Death-1, PD-L1: Programmed cell death ligand 1, CTLA4: Cytotoxic T-Lymphocyte Antigen 4, HAI: Hospital-Acquired Infection.

Figure 2. Septic shock patients stratification based on a biomarker: one virtual cohort based on real data

Based on personal data, one hundred septic shock patients were included in a virtual clinical study and monitored at Day 1-2, Day 3-5 and Day 7-10 for Human Leukocyte Antigen-DR expression on circulating monocytes [9,32]. Results are expressed as number of anti-HLA-DR antibodies bound per monocytes (AB/C). Patients are stratified based on mHLA-DR measured at Day3-5 (mHLA-DR threshold = 8 000 AB/C [39]). Twenty-eight day mortality is 34% (i.e. n = 34 non-survivors in total). Only 8 deaths occur within the first 3 days. Ninety-eight patients are still alive at Day 4 and could be stratified. Decreased mHLA-DR is observed in 55 patients. In this subgroup, 22 deaths occur (i.e. 65% of total mortality). This virtual cohort based on real observations illustrates that a decreased mHLA-DR identifies a subgroup of septic shock patients at high risk of death or secondary infection. In this subpopulation, there is a strong rational for the initiation of innovative immune stimulating therapies.