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