| 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; de la Torre Terrón, MC; Ebelt, H; Rademaker, E; Bodelsson, M; Tverring, J; Mi, Y; Knight, JC; Lindsey, ML; Langley, RJ; Kingsmore, SF; Brealey, D; Singer, M; Arulkumaran, N |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2026 |
| Collection: |
St George's University of London: Repository |
| 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 |
| File Description: |
application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| Language: |
English |
| ISSN: |
1364-8535 |
| Relation: |
https://openaccess.sgul.ac.uk/id/eprint/118227/1/Systemic%20review%20on%20sepsis%202025.pdf; https://openaccess.sgul.ac.uk/id/eprint/118227/3/13054_2025_5758_MOESM1_ESM.docx; Villa, A; Dewar, F; Pisciotta, W; Rai, A; Kerneis, S; Batum, G; McDonnell, T; Scully, M; McHugh, TD; Hilpert, K; et al. 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; de la Torre Terrón, MC; Ebelt, H; Rademaker, E; Bodelsson, M; Tverring, J; Mi, Y; Knight, JC; Lindsey, ML; Langley, RJ; Kingsmore, SF; Brealey, D; Singer, M; Arulkumaran, N (2026) Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis. Critical Care, 30. p. 41. ISSN 1364-8535 https://doi.org/10.1186/s13054-025-05758-0 SGUL Authors: Hilpert, Kai |
| DOI: |
10.1186/s13054-025-05758-0 |
| Availability: |
https://openaccess.sgul.ac.uk/id/eprint/118227/; https://openaccess.sgul.ac.uk/id/eprint/118227/1/Systemic%20review%20on%20sepsis%202025.pdf; https://openaccess.sgul.ac.uk/id/eprint/118227/3/13054_2025_5758_MOESM1_ESM.docx; https://doi.org/10.1186/s13054-025-05758-0 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.B74622C3 |
| Database: |
BASE |