Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial

Laura Alagna,Giacomo Bellani,Giacomo Grasselli,Stefano Romagnoli,Luigi Vivona,Pietro Caironi,Barbara Bottazzi,Fabio Silvio Taccone ,Jennifer Meessen ,Federica Motta ,Nicolò M Agnelli ,W Taccone ,Alessandra Bandera,Irene Principale,Andrea Cortegiani,Francesca Di Marzo Capozzi,Vieri Parrini,Roberto Keim,Daniela Albiero,Roberto Latini

doi:10.1186/s13613-021-00952-z

Abstract

BackgroundThe role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits. We aimed to elucidate the possible association and clinical significance between circulating levels of immunoglobulins.MethodsIn a subset of 956 patients with severe sepsis and septic shock of the multicentre, open-label RCT ALBIOS, venous blood samples were serially collected 1, 2, and 7 days after enrolment (or at ICU discharge, whichever came first). IgA, IgG and IgM concentrations were assayed in all patients on day 1 and in a subgroup of 150 patients on days 2 and 7. Ig concentrations were measured employing a turbidimetric assay, OSR61171 system.ResultsIgA on day 1 had a significant predictive value for both 28-day and 90-day mortality (28-day mortality, HR: 1.50 (95% CI 1.18–1.92); 90-day mortality, HR: 1.54 (95% CI 1.25–1.91)). IgG, but not IgM, on day 1 showed similar results for 28-day (HR 1.83 (95% CI 1.33–2.51) and 90-day mortality HR: 1.66 (95% CI 1.23–2.25)). In addition, lower levels of IgG but not of IgA and IgM, at day 1 were associated with significantly higher risk of secondary infections (533 [406–772] vs 600 [452–842] mg/dL, median [Q1–Q3], p = 0.007).ConclusionsIn the largest cohort study of patients with severe sepsis or septic shock, we found that high levels of IgA and IgG on the first day of diagnosis were associated with a decreased 90-day survival. No association was found between IgM levels and survival. As such, the assessment of endogenous immunoglobulins could be a useful tool to identify septic patients at high risk of mortality.Trial registration #NCT00707122, Clinicaltrial.gov, registered 30 June 2008

Highlights

The role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits
When stratifying patients according to immunoglobulin levels, patients with the highest Immunoglobulin A (IgA), Immunoglobulin G (IgG) or Immunoglobulin M (IgM) had higher white blood cell count
Mortality was higher in the high range of IgA and IgG, but no difference was found for IgM

Summary

Introduction

The role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits. Sepsis is one of the main causes of admission to intensive care unit (ICU) [1] Both sepsis and septic shock are associated with an increased risk of death, with septic shock showing a mortality rate of more than 50% [2]. Alagna et al Annals of Intensive Care (2021) 11:161 and septic shock are early recognition and resuscitation, source of infection control, adequate antibiotic therapy, achieving hemodynamic stability, and support of failing organs [3]. These measures and clinical therapies do not counter the inflammatory imbalance and the immunological dysregulation, including the subsequent prolonged immunosuppression, very often characterizing sepsis and septic shock [4, 5]. Low immunoglobulin levels during sepsis have been associated with poor outcome, suggesting the hypothesis that endogenous immunoglobulin replacement during sepsis may improve survival [8, 9]

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