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

Author

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

Subjects
IgA, IgG, IgM Immunoglobulins, Mortality, Septic shock, Sepsis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background The 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. Methods In 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. Results IgA 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). Conclusions In 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

Published
2021
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2. Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial

Author

Walter Taccone, Andrea Cortegiani, Irene Principale, Pietro Caironi, Roberto Latini, Barbara Bottazzi, Francesca Motta, Laura Alagna, Fabio Silvio Taccone, Giacomo Grasselli, Luigi Vivona, Alessandra Bandera, Nicolò M Agnelli, Francesca Di Marzo Capozzi, Jennifer Meessen, Roberto Keim, Vieri Parrini, Giacomo Bellani, Daniela Albiero, Stefano Romagnoli, Alagna, L, Meessen, J, Bellani, G, Albiero, D, Caironi, P, Principale, I, Vivona, L, Grasselli, G, Motta, F, Agnelli, N, Parrini, V, Romagnoli, S, Keim, R, Di Marzo Capozzi, F, Taccone, F, Taccone, W, Bottazzi, B, Bandera, A, Cortegiani, A, Latini, R, Alagna, Laura, Meessen, Jennifer M T A, Bellani, Giacomo, Albiero, Daniela, Caironi, Pietro, Principale, Irene, Vivona, Luigi, Grasselli, Giacomo, Motta, Francesca, Agnelli, Nicolò M, Parrini, Vieri, Romagnoli, Stefano, Keim, Roberto, Di Marzo Capozzi, Francesca, Taccone, Fabio S, Taccone, Walter, Bottazzi, Barbara, Bandera, Alessandra, Cortegiani, Andrea, and Latini, Roberto

Subjects
medicine.medical_specialty, Sepsi, IgG, Secondary infection, Critical Care and Intensive Care Medicine, Gastroenterology, law.invention, Sepsis, Randomized controlled trial, law, Internal medicine, Septic shock, Risk of mortality, medicine, Clinical significance, Mortality, business.industry, RC86-88.9, Research, Medical emergencies. Critical care. Intensive care. First aid, Venous blood, medicine.disease, IgM Immunoglobulins, business, IgA, IgM Immunoglobulin, Cohort study
Abstract

Background The 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. Methods In 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. Results IgA 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). Conclusions In 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

Published
2021

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