An integrative model with HLA‐DR, CD64, and PD‐1 for the diagnostic and prognostic evaluation of sepsis

• Published in: Immunity, Inflammation and Disease Vol. 12; no. 1; pp. e1138 - n/a
• Main Authors: Chen, Guosheng, Chong, Huimin, Zhang, Peng, Wen, Dalin, Du, Juan, Gao, Chu, Zeng, Shi, Zeng, Ling, Deng, Jin, Zhang, Kejun, Zhang, Anqiang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2024; John Wiley and Sons Inc; Wiley
• Subjects: Antibodies; Biomarkers; Case-Control Studies; CD64; Critical Illness; Disease; Flow cytometry; HLA-DR Antigens; HLA‐DR; Humans; Infections; Medical prognosis; Microorganisms; Mortality; Original; PD‐1; predict; Prognosis; Programmed Cell Death 1 Receptor; Sepsis; Sepsis - diagnosis; Software; CD64; predict; HLA-DR; PD-1; sepsis
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.1138

Background Sepsis is a life‐threatening organ dysfunction caused by a dysregulated host response to infection and progressive immunosuppression with high mortality. HLA‐DR, CD64, and PD‐1 were assumed to be useful biomarkers for sepsis prediction. However, the ability of a combination of these biomarkers has not been clarified. Methods An observational case‐control study was conducted that included 30 sepsis patients, 30 critically ill patients without sepsis admitted to the intensive care unit (ICU), and 32 healthy individuals. The levels of HLA‐DR, CD64, and PD‐1 expression in peripheral blood immune cells and subsets was assayed on Days 1, 3, and 5, and the clinical information of patients was collected. We compared these biomarkers between groups and evaluated the predictive validity of single and combined biomarkers on sepsis mortality. Results The results indicate that PD‐1 expression on CD4−CD8−T (PD‐1+CD4−CD8−T) (19.19% ± 10.78% vs. 9.88% ± 1.79%, p = .004) cells and neutrophil CD64 index (nCD64 index) (9.15 ± 5.46 vs. 5.33 ± 2.34, p = .001) of sepsis patients were significantly increased, and HLA‐DR expression on monocytes (mHLA‐DR+) was significantly reduced (13.26% ± 8.06% vs. 30.17% ± 21.42%, p = 2.54 × 10−4) compared with nonsepsis critically ill patients on the first day. Importantly, the expression of PD‐1+CD4−CD8−T (OR = 0.622, 95% CI = 0.423–0.916, p = .016) and mHLA‐DR+ (OR = 1.146, 95% CI = 1.014–1.295, p = .029) were significantly associated with sepsis mortality. For sepsis diagnosis, the mHLA‐DR+, PD‐1+CD4−CD8−T, and nCD64 index showed the moderate individual performance, and combinations of the three biomarkers achieved greater diagnostic value (AUC = 0.899, 95% CI = 0.792–0.962). When adding PCT into the combined model, the AUC increased to 0.936 (95% CI = 0.840–0.983). For sepsis mortality, combinations of PD‐1+CD4−CD8−T and mHLA‐DR+, have a good ability to predict the prognosis of sepsis patients, with an AUC = 0.921 (95% CI = 0.762–0.987). Conclusion These findings indicate that the combinations of HLA‐DR, CD64, and PD‐1 outperformed each of the single indicator in diagnosis and predicting prognosis of sepsis. mHLA‐DR+ and CD3 + CD4−CD8−CD279+ together provide good predictive ability for ICU mortality among subjects with sepsis. The performance of mHLA‐DR+ and CD3 + CD4−CD8−CD279+ in this cohort rivals established clinical‐ and biomarker‐based tools for mortality risk stratification in sepsis. Further study should be directed toward validating mHLA‐DR+ and CD3 + CD4−CD8−CD279+ for sepsis prognosis and assessing the additive value of mHLA‐DR+ or CD3 + CD4−CD8−CD279+ in combination with predictive clinical features. Highlights The present results have shown that three biomarkers of immunosuppression may serve as diagnostic or prognostic markers for septic patients. This was based on the following findings: (1) the percentage of mHLA‐DR+ and PD‐1 + CD4−CD8− T cells and the neutrophil CD64 index were significantly different between patients with and without sepsis; furthermore, the percentage of mHLA‐DR+ and PD‐1 + CD4‐CD8‐ T cells was also significantly different between septic patients with and without death in the ICU; (2) there was a significant gain in discriminative power of diagnostic or prognostic sepsis markers when the linear combination that yielded the highest AUC was employed. mHLA‐DR+ and PD‐1 + CD4‐CD8‐T together provide good predictive ability for ICU mortality among subjects with sepsis. The performance of mHLA‐DR+ and PD‐1 + CD4‐CD8‐T in this cohort rivals established clinical‐ and biomarker‐based tools for mortality prediction in sepsis.