| Title: |
Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis |
| Authors: |
Villa,Antoine; Dewar,Fiona; Pisciotta,Walter; Rai,Ankit; Kerneis,Sven; Batum,Gül; McDonnell,Tom; Scully,Marie; McHugh,Timothy D; Hilpert,Kai; Gilroy,Derek; de Nooijer,Aline; Netea,Mihai G; Hedetoft,Morten; Bermejo-Martin,Jesús F; Akatsuka,Masayuki; Heinz,Corina C; Venet,Fabienne; Monneret,Guillaume; Meessen,Jennifer; Cheng,Tzu Hsuan; Zhang,Ming; Caironi,Pietro; Giamarellos-Bourboulis,Evangelos J; de la Torre Terrón,Mari C; Ebelt,Henning; Rademaker, Emma; Bodelsson,Mikael; Tverring,Jonas; Mi,Yuxin; Knight,Julian C; Lindsey,Merry L; Langley,Raymond J; Kingsmore,Stephen F; Brealey,Dave; Singer,Mervyn; Arulkumaran,Nishkantha; Sepsis and Inflammation |
| Publication Year: |
2026 |
| Subject Terms: |
Journal Article |
| 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 |
| Language: |
English |
| ISSN: |
1466-609X |
| Relation: |
https://dspace.library.uu.nl/handle/1874/469028 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/469028 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.F7EC3CF8 |
| Database: |
BASE |