Soluble ST2 predicts ARDS ICU mortality

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ST2 could have useful prognostic value

Dr. Eleanor Summerhill, FCCP, comments: A recently discovered

member of the IL-1 superfamily of cytokines, IL-33 has been shown to

have multiple immunomodulatory effects, but predominately induces the

T–helper cell (TH-2) pathway. The soluble isoform of the IL-1 receptor

(ST2) acts as a "decoy receptor" for IL-33, dampening the

pro-inflammatory response. A growing body of evidence suggests that

plasma levels of ST2 may serve as a useful biomarker in cardiac,

rheumatologic, and pulmonary disease, including asthma, pulmonary

fibrosis, eosinophilic pneumonia, and ALI/ARDS.

Dr. Garcia-Acilu

and colleagues recently reported the results of a small, single-center

study evaluating the prognostic value of soluble ST2 levels on day 1 in

patients with ARDS, and found that the use of this biomarker

outperformed both the APACHE II and SOFA scores in predicting mortality.

There is also some evidence in the literature that modulation of

soluble ST2 levels may be useful as a therapeutic modality.


is a very exciting new area of investigation with significant potential

impact on the future management of patients with ARDS.



MADRID – Elevated levels of the soluble ST2 protein were associated with higher intensive care unit mortality in patients with acute respiratory distress syndrome in a prospective pilot study.

Among 62 patients, median soluble ST2 levels were significantly higher among ICU nonsurvivors than survivors on day 1 of acute respiratory distress syndrome (ARDS) onset (4,934 pg/mL vs. 1,007 pg/mL) and at day 3 (5,720 pg/mL vs. 823 pg/mL), Dr. Marina Garcia de Acilu reported at CHEST World Congress 2014.

The soluble form of the ST2 [interleukin-1 (IL-1) receptor-like 1] protein, and its ligand, IL-33, have come under increased scrutiny in recent years for their potential role in the pathogenesis of various pulmonary diseases including ARDS.

ST2 concentrations have been reported to be elevated in patients with asthma, pulmonary fibrosis, and eosinophilic pneumonia, and were shown in the PRIDE (ProBNP Investigation of Dyspnea in the Emergency Department) study to predict 1-year survival among acutely dyspneic patients with pulmonary disorders admitted to the emergency department (Am. J. Clin. Pathol. 2008;130:578-584) from September 2012 to September 2013. Their median APACHE II (Acute Physiology and Chronic Health Evaluation II) score was 24 (range 19-29) and their median age was 61 years. ICU mortality was 41%.

No significant differences were seen in IL-33 concentrations on day 1 or 3 between survivors and those who died, reported Dr. Garcia de Acilu of Vall d’Hebron University Hospital, Barcelona.

An ST2 level on day 1 of at least 3,672 pg/mL, however, accurately identified patients who died (area under the operator curve 0.96; P less than .01), and outperformed traditional APACHE and SOFA (Sequential Organ Failure Assessment) scores, with a sensitivity of 86% and specificity of 100%.

Patients with an ST2 level below this threshold on day 1 had significantly higher survival rates in a Kaplan-Meier survival analysis.

In addition, an ST2 level above 3,672 pg/mL on day 1 was the only variable in multivariate analysis associated with ICU mortality, increasing the risk of death more than 14-fold (hazard ratio, 14.7), Dr. Garcia de Acilu reported in the poster presentation.

"In ARDS patients, ST2 may be considered a useful early biomarker for prognosis, by identifying high-risk-of-death patients," the authors concluded. "Further studies, using ST2 clinically, should be performed to assess the added value in specific subpopulations or in the presence of some comorbidities."

ST2 may also prove useful as a therapeutic strategy. A recent study, also out of Barcelona, reported that human mesenchymal stem cells, genetically engineered to produce soluble ST2, further prevented IL-33 induction, but also enhanced IL-10 expression in a murine acute lung injury model. This synergy led to a substantial decrease in lung airspace inflammation and vascular leakage (Am. J. Respir. Cell Mol. Biol. 2013:49:552-62).

"This study also illustrates the potential role for targeting ST2 as a therapy for airway disorders," senior author Dr. Jordi Rello, chief of critical care at Vall d’Hebron University Hospital, said in an interview.

Dr. Garcia de Acilu and her coauthors reported no financial disclosures.

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