Circulating cell-death-associated biomarkers and inflammatory severity in Hymenoptera sting envenomation: a single-center retrospective study.
- 1Department of Emergency Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
Abstract
Severe Hymenoptera sting envenomation can cause systemic inflammation, shock, and multi-organ injury. Gasdermin D cleavage and RIPK3 phosphorylation are associated with inflammatory cell-death pathways, but circulating measurements cannot by themselves establish a specific cellular death mechanism. We therefore evaluated the clinical associations of serum GSDMD-p30, p-RIPK3, IL-1β, and IL-18 with illness severity in patients with Hymenoptera sting envenomation. We conducted a single-center retrospective study of 142 adults admitted between January 2023 and December 2025. Clinical severity was categorized at admission using a four-level institution-specific scheme: Grade I, local/minimal systemic manifestations without organ dysfunction; Grade II, systemic allergic manifestations without organ dysfunction; Grade III, single-organ failure; and Grade IV, multi-organ failure and/or anaphylactic shock. Archived serum was available for 98 patients (Grade I/II/III/IV: 30/33/22/13). Serum GSDMD-p30, p-RIPK3, IL-1β, and IL-18 were measured by ELISA-based assays. Associations with severity grade and SOFA score and exploratory same-cohort ROC performance for Grade III-IV disease were assessed. The cohort included 42 Grade I, 48 Grade II, 34 Grade III, and 18 Grade IV patients. Sting count, time to hospital presentation, inflammatory indices, organ-injury markers, SOFA score, ICU admission, and length of stay increased with clinical severity. In the serum subset, mean GSDMD-p30 increased from 0.82 ± 0.21 ng/mL in Grade I to 9.43 ± 2.18 ng/mL in Grade IV, and p-RIPK3 increased from 0.64 ± 0.18 to 7.84 ± 1.87 ng/mL (global p < 0.001 for both). IL-1β and IL-18 showed similar severity-associated increases. Correlations with SOFA score were ρ = 0.814 for GSDMD-p30, ρ = 0.783 for p-RIPK3, ρ = 0.791 for IL-18, and ρ = 0.762 for IL-1β (all p < 0.001). Apparent AUCs for Grade III-IV disease were 0.861, 0.843, 0.834, and 0.812, respectively. Circulating GSDMD-p30, p-RIPK3, IL-1β, and IL-18 were associated with clinical severity and organ-failure burden in this retrospective cohort. These findings support further evaluation of these proteins as candidate severity-associated biomarkers, but they do not demonstrate PANoptosis, establish cell-specific origin, or validate a clinical triage tool. Prospective multicenter studies with standardized assays and adjusted analyses are required.
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BibTeX
@article{bian2026circulating,
title = {{Circulating cell-death-associated biomarkers and inflammatory severity in Hymenoptera sting envenomation: a single-center retrospective study.}},
author = {Pan Bian and Yuhua Wang and Shaohui Zhang and Yang Gui and Zhenya Shen},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1970146},
url = {https://europepmc.org/article/MED/42952992},
note = {CC BY},
}
RIS
TY - JOUR
TI - Circulating cell-death-associated biomarkers and inflammatory severity in Hymenoptera sting envenomation: a single-center retrospective study.
AU - Pan Bian
AU - Yuhua Wang
AU - Shaohui Zhang
AU - Yang Gui
AU - Zhenya Shen
PY - 2026
DA - 2026/10/14
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1970146
UR - https://europepmc.org/article/MED/42952992
AB - Severe Hymenoptera sting envenomation can cause systemic inflammation, shock, and multi-organ injury. Gasdermin D cleavage and RIPK3 phosphorylation are associated with inflammatory cell-death pathways, but circulating measurements cannot by themselves establish a specific cellular death mechanism. We therefore evaluated the clinical associations of serum GSDMD-p30, p-RIPK3, IL-1β, and IL-18 with illness severity in patients with Hymenoptera sting envenomation. We conducted a single-center retrospective study of 142 adults admitted between January 2023 and December 2025. Clinical severity was categorized at admission using a four-level institution-specific scheme: Grade I, local/minimal systemic manifestations without organ dysfunction; Grade II, systemic allergic manifestations without organ dysfunction; Grade III, single-organ failure; and Grade IV, multi-organ failure and/or anaphylactic shock. Archived serum was available for 98 patients (Grade I/II/III/IV: 30/33/22/13). Serum GSDMD-p30, p-RIPK3, IL-1β, and IL-18 were measured by ELISA-based assays. Associations with severity grade and SOFA score and exploratory same-cohort ROC performance for Grade III-IV disease were assessed. The cohort included 42 Grade I, 48 Grade II, 34 Grade III, and 18 Grade IV patients. Sting count, time to hospital presentation, inflammatory indices, organ-injury markers, SOFA score, ICU admission, and length of stay increased with clinical severity. In the serum subset, mean GSDMD-p30 increased from 0.82 ± 0.21 ng/mL in Grade I to 9.43 ± 2.18 ng/mL in Grade IV, and p-RIPK3 increased from 0.64 ± 0.18 to 7.84 ± 1.87 ng/mL (global p < 0.001 for both). IL-1β and IL-18 showed similar severity-associated increases. Correlations with SOFA score were ρ = 0.814 for GSDMD-p30, ρ = 0.783 for p-RIPK3, ρ = 0.791 for IL-18, and ρ = 0.762 for IL-1β (all p < 0.001). Apparent AUCs for Grade III-IV disease were 0.861, 0.843, 0.834, and 0.812, respectively. Circulating GSDMD-p30, p-RIPK3, IL-1β, and IL-18 were associated with clinical severity and organ-failure burden in this retrospective cohort. These findings support further evaluation of these proteins as candidate severity-associated biomarkers, but they do not demonstrate PANoptosis, establish cell-specific origin, or validate a clinical triage tool. Prospective multicenter studies with standardized assays and adjusted analyses are required.
SN - 2296-634X
ER -