| Title: |
Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis |
| Authors: |
Villa, A; Dewar, F; Pisciotta, W; Rai, A; Kerneis, S; Batum, G; McDonnell, T; Scully, M; McHugh, TD; Hilpert, K; Gilroy, D; de Nooijer, A; Netea, MG; Hedetoft, M; Bermejo-Martin, JF; Akatsuka, M; Heinz, CC; Venet, F; Monneret, G; Meessen, J; Cheng, TH; Zhang, M; Caironi, P; Giamarellos-Bourboulis, EJ; Mi, Y; Knight, JC |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2026 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Purpose: Humoral 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. Methods: We 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. Results: Thirty-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. Conclusion: Sepsis 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1186/s13054-025-05758-0 |
| Availability: |
https://doi.org/10.1186/s13054-025-05758-0; https://ora.ox.ac.uk/objects/uuid:17c814f8-fbce-4dce-b9d5-011ce3d3a0ce |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.B5FD7B2A |
| Database: |
BASE |