Utility of neutrophil CD64 in distinguishing bacterial infection from inflammation in severe alcoholic hepatitis fulfilling SIRS criteria

Gaurav Pandey,Prabhakar Mishra,Alok Kumar,Arun Bhadauria,Durga Prasanna Misra,Ravi Mishra,V P Krishna,Samir Mohindra,Manjunath Hatti,Saurabh Chaturvedi,Vikas Agarwal,Harshit Singh,Vivek Anand Saraswat

doi:10.1038/s41598-021-99276-y

Gaurav Pandey, Prabhakar Mishra + Show 11 more

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https://doi.org/10.1038/s41598-021-99276-y

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Abstract

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil–lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9–86.5) vs. 16% (12.6–23.1) vs. 7.05% (1.4–9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229–1828) vs. 853 (20–968) vs. 99.5 (54.7–140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers.

Highlights

To assess utility of neutrophilCD64 expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria
Increased susceptibility to bacterial infections in SAH is due to endotoxin induced neutrophil s uppression7 and high expression of inhibitory receptors on lymphocytes, programmed cell death 1 (PD1), T-cell immunoglobulin and mucin domain–containing protein 3 (TIM3) and their ligands PD ligand 1 (PDL-1) and galectin-9, r espectively8
We have evaluated the clinical usefulness of quantitative nCD64 measurements to differentiate between systemic bacterial infection and active inflammation in patients with SAH

Summary

Introduction

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with SAH, which may be up to 30% at 2-months.The STOPAH trial had 24% incidence of severe infections in S AH5.The systemic inflammatory response syndrome (SIRS) is often present at admission and has an independent association with. Increased susceptibility to bacterial infections in SAH is due to endotoxin induced neutrophil s uppression and high expression of inhibitory receptors on lymphocytes, programmed cell death 1 (PD1), T-cell immunoglobulin and mucin domain–containing protein 3 (TIM3) and their ligands PD ligand 1 (PDL-1) and galectin-9, r espectively. Higher expression of inhibitory receptors on lymphocytes and neutrophil dysfunction may result in immune paralysis and increased susceptibility to infections.The phenomenon of T cell exhaustion in SAH and impaired adaptive and innate immunity in acute AH have been well d ocumented

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