脓毒症诱导免疫抑制中免疫调节与巨细胞病毒再激活：一项初步研究

Immune Modulation and Cytomegalovirus Reactivation in Sepsis-induced Immunosuppression: A Pilot Study.

作者信息

Lambe Gaurav, Mansukhani Dia, Khodaiji Shanaz, Shetty Anjali, Rodrigues Camilla, Kapadia Farhad

机构信息

Department of Laboratory Medicine, PD Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India; Department of Critical Care, PD Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India.

Department of Laboratory Medicine, PD Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India.

出版信息

Indian J Crit Care Med. 2022 Jan;26(1):53-61. doi: 10.5005/jp-journals-10071-24079.

DOI:10.5005/jp-journals-10071-24079

PMID:35110845

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8783232/

Abstract

INTRODUCTION

Sepsis is a life-threatening condition caused due to dysregulated immune response to an infection and progressive immunosuppression. Reactivation of cytomegalovirus (CMV) occurs frequently in sepsis and is found associated with adverse outcomes. The study objective was to evaluate the association between incidence of CMV reactivation and immune alteration in sepsis-induced immunosuppression in patients with prolonged sepsis.

PATIENTS AND METHODS

Patients admitted to intensive care unit (ICU), with severe sepsis and CMV immunoglobulin G (IgG) seropositivity, were prospectively enrolled. Other manifest immune suppression causes were excluded. Samples were collected on enrolment and further once a week until day 21 or death/discharge. CMV viral load was quantified using qPCR. Lymphocyte subset analysis (CD3+, CD4+, CD8+, CD19+, CD16+/CD56+, and CD25+CD127- regulatory T cells), human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes, programmed death-1 (PD-1) expression on T lymphocytes, and proinflammatory (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)), anti-inflammatory cytokines levels (IL-2, IL-4, and IL-10) were analyzed by flow cytometry as markers for immunosuppression.

RESULTS

A total of 25 CMV IgG-positive patients and 11 healthy controls were included. CMV reactivation occurred in 20 patients. Patients with CMV reactivation had T-cell lymphopenia. PD-1 expression on CD4+ and CD8+ T cells was markedly elevated ( <0.02) in CMV-reactivated patients compared to nonreactivated patients. HLA-DR expression was significantly low on monocytes in all septic patients ( <0.01) compared to healthy controls. IL-6 levels showed elevation at day 7, whereas IL-10 was found to be significantly higher from day 0 in CMV-reactivated group.

CONCLUSION

Our study concluded that immune suppression markers and cytokine levels in patients with severe sepsis were found to be significantly associated with the incidence of CMV reactivation.

HOW TO CITE THIS ARTICLE

Lambe G, Mansukhani D, Khodaiji S, Shetty A, Rodrigues C, Kapadia F. Immune Modulation and Cytomegalovirus Reactivation in Sepsis-induced Immunosuppression: A Pilot Study. Indian J Crit Care Med 2022;26(1):53-61.

摘要

引言

脓毒症是一种危及生命的病症，由对感染的免疫反应失调和进行性免疫抑制引起。巨细胞病毒（CMV）再激活在脓毒症中频繁发生，且与不良预后相关。本研究的目的是评估长期脓毒症患者中CMV再激活的发生率与脓毒症诱导的免疫抑制中免疫改变之间的关联。

患者与方法

前瞻性纳入入住重症监护病房（ICU）、患有严重脓毒症且CMV免疫球蛋白G（IgG）血清学阳性的患者。排除其他明显的免疫抑制原因。在入组时采集样本，之后每周采集一次，直至第21天或死亡/出院。使用定量聚合酶链反应（qPCR）对CMV病毒载量进行定量。通过流式细胞术分析淋巴细胞亚群（CD3 +、CD4 +、CD8 +、CD19 +、CD16 + / CD56 +以及CD25 + CD127 -调节性T细胞）、单核细胞上人类白细胞抗原-DR同种型（HLA-DR）的表达、T淋巴细胞上程序性死亡-1（PD-1）的表达以及促炎细胞因子（白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ））、抗炎细胞因子水平（IL-2、IL-4和IL-10），作为免疫抑制的标志物。

结果

共纳入25例CMV IgG阳性患者和11例健康对照。20例患者发生CMV再激活。发生CMV再激活的患者存在T细胞淋巴细胞减少。与未再激活的患者相比，CMV再激活患者的CD4 +和CD8 + T细胞上PD-1的表达显著升高（<0.02）。与健康对照相比，所有脓毒症患者单核细胞上的HLA-DR表达均显著降低（<0.01）。IL-6水平在第7天升高，而在CMV再激活组中，IL-10从第0天起就显著升高。