Evidence map›Paper›PMID 41430733›Full record

SynthesisCritical care (London, England)2025

Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis.

Antoine Villa, Fiona Dewar, Walter Pisciotta, Ankit Rai, Sven Kerneis, Gül Batum, Tom McDonnell, Marie Scully, Timothy D McHugh, Kai Hilpert and 27 more

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Critical care (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Observational
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

37 authors.

Antoine VillaBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Fiona DewarBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Walter PisciottaBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Ankit RaiBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Sven KerneisBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Gül BatumBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Tom McDonnellInstitute of Inflammation and Repair, University College London, London, UK.
Marie ScullyDepartment of Haematology, UCLH and Haematology Programme-NIHR UCLH/UCL BRC, London, UK.
Timothy D McHughCentre for Clinical Microbiology, Division of Infection and Immunity, University College London, London, UK.
Kai HilpertInstitute for Infection and Immunity, St George's, University of London, London, UK.
Derek GilroyCentre for Clinical Pharmacology, University College London, London, UK.
Aline de NooijerDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
Mihai G NeteaDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
Morten HedetoftDepartment of Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jesús F Bermejo-MartinUniversidad de Salamanca & Instituto de Investigación Biomédica de Salamanca (IBSAL) & CIBERES, Instituto de Salud Carlos III, Madrid, Spain.
Masayuki AkatsukaDepartment of Biochemistry, Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Corina C HeinzDepartment of Clinical Research and Development, Biotest, Dreieich, AG, Germany.
Fabienne VenetCIRI, Centre International de Recherche en Infectiologie, Inserm U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, F-69007, France.
Guillaume MonneretLaboratoire d'Immunologie, Hôpital E. Herriot, Hospices Civils de Lyon, Lyon, France.
Jennifer MeessenDepartment of Acute, Brain and Cardiovascular Injury, Institute for Pharmacological Research Mario Negri IRCCS, Milan, Italy.
Tzu Hsuan ChengDepartment of Anesthesiology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Ming ZhangDepartment of Anesthesiology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Pietro CaironiDepartment of Acute, Brain and Cardiovascular Injury, Institute for Pharmacological Research Mario Negri IRCCS, Milan, Italy.
Evangelos J Giamarellos-BourboulisDepartment of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Mari C de la Torre TerrónDepartment of Intensive Care Medicine, Hospital Universitari de Mataró, Consorci Sanitari del Maresme, Mataró, Spain.
Henning EbeltDepartment of Internal Medicine III, University Hospital Halle (Saale), Catholic Hospital St. Johann Nepomuk, Halle, Erfurt, Germany.
Emma RademakerDepartment of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Mikael BodelssonDepartment of Clinical Sciences, Lund University, Lund, Sweden.
Jonas TverringDepartment of Clinical Sciences, Lund University, Lund, Sweden.
Yuxin MiCentre for Human Genetics, University of Oxford, Oxford, UK.
Julian C KnightCentre for Human Genetics, University of Oxford, Oxford, UK.
Merry L LindseyDepartment of Applied Education, Department of Biomedical Sciences, Meharry Medical College, Nashville, TN, USA.
Raymond J LangleyDepartment of Pharmacology, Whiddon College of Medicine, University of South Alabama, Mobile, AL, USA.
Stephen F KingsmoreRady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, USA.
Dave BrealeyBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Mervyn SingerBloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
Nishkantha ArulkumaranBloomsbury Institute of Intensive Care Medicine, University College London, London, UK. n.arulkumaran@ucl.ac.uk.ORCID http://orcid.org/0009-0008-2222-3180

Funding

Medical Research Council W030489/1
6 · The paper itself

Abstract

purposeHumoral immunity proteins-immunoglobulins, complement proteins, and antimicrobial peptides-have key antimicrobial and immunomodulatory functions in sepsis. We hypothesised that their circulating levels are lower in non-survivors, potentially resulting in impaired bacterial clearance and persistent or recurrent infections.

methodsWe performed a systematic review and meta-analysis evaluating differences in humoral immunity proteins between survivors and non-survivors in adult patients with sepsis. PubMed and Embase were searched without date restrictions. Random-effects meta-analyses were used to estimate pooled standardised mean differences (SMD) with 95% confidence intervals (CI). Sensitivity analyses included data from the MIMIC-IV ICU database, and further supplemented by three proteomic studies.

resultsThirty-six studies including 6,330 patients were analysed. Thirteen reported on immunoglobulins, 17 on complement proteins, and 7 on the antimicrobial peptide heparin-binding protein (HBP). Survivors had significantly higher levels of complement proteins C3 (SMD 0.53 [0.07-0.99]) and C4 (SMD 0.51 [0.09-0.94]) compared to non-survivors. Conversely, C4a (SMD - 1.17 [-1.77 to - 0.56]) and IgA (SMD - 0.21 [-0.39 to - 0.03]) were significantly lower in survivors. No differences were found for IgG (SMD 0.00 [-0.18 to 0.18]), IgM (SMD - 0.02 [-0.13 to 0.08]), C5, C5a, or HBP. Sensitivity analyses using MIMIC-IV (n = 2,452) and proteomic datasets supported these findings. Proteomic data revealed early depletion of classical complement components (C3, C4B) and regulatory proteins in non-survivors.

conclusionSepsis non-survivors exhibit lower C3 and C4 levels and higher C4a, consistent with complement activation and/or depletion. Complement proteins may serve as potential biomarkers and therapeutic targets in sepsis.

Indexed as

Complement System ProteinsImmunity, HumoralSepsisAntimicrobial PeptidesHumansImmunoglobulinsAntimicrobial PeptidesComplement System ProteinsImmunoglobulinsComplementHumoral immunityICUImmunoglobulinsMortalitySepsis

Identifiers

PMID41430733
PMCPMC12837105

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.