Dataset Information

Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS.

ABSTRACT: CD74 is expressed on the cell surface of pulmonary macrophages and contributes to macrophage migration inhibitory factor (MIF)-induced inflammatory response in acute lung injury (ALI). A circulating form of CD74 (soluble CD74, sCD74) was recently discovered in autoimmune liver disease. Using two murine ALI models and cells culture, we examined the presence of sCD74 in circulation and alveolar space and preliminarily assessed the biological function of sCD74. The concentrations of sCD74 were increased in serum and bronchoalveolar lavage fluids (BALF) of murine ALI models. The elevated levels of sCD74 in BALF positively correlated with lung permeability and inflammation. In addition, sCD74 is secreted by macrophages in response to MIF stimulation and itself can stimulate the production of inflammatory cytokines. Our clinical study confirmed some findings of basic research. Moreover, we also found Day 3 serum sCD74 levels were associated with worse clinical outcomes. In conclusion, higher serum sCD74 levels may reflect more severe lung injury and may be used to help physicians determine prognosis of acute respiratory distress syndrome (ARDS).

SUBMITTER: Wu G

PROVIDER: S-EPMC4957083 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS.

Wu Guosheng G Sun Yu Y Wang Kang'an K Chen Zhengli Z Wang Xingtong X Chang Fei F Li Ting T Feng Ping P Xia Zhaofan Z

Scientific reports 20160722

CD74 is expressed on the cell surface of pulmonary macrophages and contributes to macrophage migration inhibitory factor (MIF)-induced inflammatory response in acute lung injury (ALI). A circulating form of CD74 (soluble CD74, sCD74) was recently discovered in autoimmune liver disease. Using two murine ALI models and cells culture, we examined the presence of sCD74 in circulation and alveolar space and preliminarily assessed the biological function of sCD74. The concentrations of sCD74 were incr ...[more]

PMID: 27444250

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Project description:BackgroundPeptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction.Methodology/principal findingsA training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity.Conclusions/significanceMALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS.

Dataset Information

Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS.

Publications

Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS.

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