CLEC4D as an Effective Indicator for Assessing Severity of Illness in Critically Ill Patients: A Prospective Study

Guangjian Wang,1,* Zhimao Li,2,* Xinyue Zhao,1 Xiaoru Wang,3 Hui Lian,1 Yecheng Liu2 1Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Emergency Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Critical Care Medicine, The Second Hospital of Shanxi Medical University, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Lian; Yecheng Liu, Email lianhui@pumch.cn; ptcaliu@sina.comBackground: Accurate assessment of illness severity is crucial in critically ill patients. The APACHE II score is widely used but complex and fails to reflect underlying immune-inflammatory dysregulation. C-type lectin domain family 4 member D (CLEC4D), a pattern recognition receptor on myeloid cells, is pivotal in immune responses. We investigated whether circulating CLEC4D levels could serve as a novel biomarker for severity of illness.Methods: 368 adult ICU patients were enrolled. Serum CLEC4D levels, APACHE II scores, and immune-inflammatory parameters were measured within 24 hours of admission. Associations were analyzed using generalized additive models and multiple linear regression.Results: Patients with high APACHE II scores (≥ 16) exhibited significantly elevated CLEC4D levels compared with those with lower scores (344.20 ± 65.75 pg/mL vs. 321.28 ± 73.31 pg/mL, P = 0.002). Multiple linear regression demonstrated a robust positive association between CLEC4D and APACHE II scores, with each 1 pg/mL increase in CLEC4D corresponding to a 0.016-point rise in APACHE II (P < 0.05). CLEC4D was inversely correlated with lymphocyte (β = − 0.028, P < 0.001) and IL-6 (β = − 1.404, P = 0.021) but positively correlated with PCT (β = 0.022, P = 0.031). Subgroup analyses confirmed the stability of this correlation across tumor and non-tumor cohorts and revealed a markedly stronger association among patients with sepsis (β = 0.030, P < 0.001).Conclusion: Circulating CLEC4D levels positively correlate with APACHE II scores in critically ill patients, potentially associated with dynamic shifts in immune-inflammatory markers. CLEC4D represents a promising biomarker for assessing illness severity, especially in sepsis.Keywords: CLEC4D, APACHE II, critically ill patients, severity of illness, biomarker, immune-inflammation