Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis
Authors' conclusion
Sepsis non-survivors exhibit lower C3 and C4 levels and higher C4a, consistent with complement activation and/or depletion.
Study context
- Population
- Adults with sepsis
- Participants
- 6,330 adults · 36 studies
- Comparison
- Survivors vs non-survivors: circulating humoral immunity protein levels
- Outcome
- Differences in humoral immunity proteins (immunoglobulins, complement proteins, antimicrobial peptides) between survivors and non-survivors (SMD)
Methodological detailsrandom-effects, sensitivity analyses with MIMIC-IV ICU database and proteomic studies, PubMed and Embase searched without date restrictions
- Random-effects
- Sensitivity analyses with MIMIC-IV ICU database and proteomic studies
- PubMed and Embase searched without date restrictions
Pooled result
As reported in the abstract
Circulating humoral immunity protein levels, survivors vs non-survivors
Survivors vs Non-survivorsSMD (95% CI)
C3; significantly higher in survivors
0.53(0.07–0.99)
C4; significantly higher in survivors
0.51(0.09–0.94)
C4a; significantly lower in survivors
- 1.17(−1.77 to - 0.56)
IgA; significantly lower in survivors
- 0.21(−0.39 to - 0.03)
- No difference for IgG
- SMD 0.00 [−0.18 to 0.18]
- No difference for IgM
- SMD - 0.02 [−0.13 to 0.08]
Further pooled results
Sensitivity analyses (MIMIC-IV and proteomic datasets)
- Supported the main findings (MIMIC-IV n = 2,452)
- Proteomic data: early depletion of classical complement components (C3, C4B) and regulatory proteins in non-survivors
Original publication
Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis. Crit Care. Published 22 December 2025. doi:10.
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