The Role and Functional Significance of Immune Regulators in Parapneumonic Effusions

Parapneumonic effusion (PPE), which occurs approximately in 40% of pneumonia patients, is an accumulation of exudative pleural fluid associated with the pulmonary infection. The morbidity and mortality of pneumonia increase when the patient presents with the PPE, because this stage correlates with more-advanced pneumonia. Based on fluid characteristics, PPEs are classified as uncomplicated parapneumonic effusions (UPPE), complicated parapneumonic effusions (CPPE), or empyema. The pneumonia patients with empyema have a 50% mortality rate. The diagnosis of PPE stages is based on multiple biochemical parameters, including white blood cell count, LDH level, glucose level, and pH value of effusions. Early antibiotic treatment usually prevents the development or progression of the PPE to CPPE and/or empyema. However, it remains the challenge for early treatment of PPE because there is no practical approach for early detection and differential diagnosis of PPE. A number of potential immune-related proteins have been evaluated in PPE. However, these markers are not used in clinical diagnosis, due to limitations in sensitivity and specificity. Also, the complete catalog of PPE proteome profiling, as well as the corresponding functional consequences, is not yet fully compiled. Thus, it is important to identify potential biosignatures to aid in distinguishing different stages and predicating outcomes of PPE. In this proposal, we are attempting to outline and execute a set of synergistic experiments to further explore the role of candidate regulators and to provide proteome-wide insights into the mechanisms and molecular consequences of candidate regulators in PPE progression. First, we will establish a comprehensive PPE proteome profiling via iTRAQ-based proteomics technology. Bioinformatic tools will be applied to reveal the complement of protein expression patterns in term of identification and quantitation, facilitating cross-sample comparison for the unbiased identification of candidate regulators. Next, the underlying molecular mechanism and cellular consequence of the candidate regulator’s functions will be thoroughly dissected via cell biological experiments. Finally, pneumonia mice model will be established for phenotypic characterization of functional outcome of candidate regulators-mediated activity in the PPE progression in vivo. Taken together, we can improve the diagnosis procedures and provide better medical therapies for pneumonia patients.

Project ID:PC10408-1731
External Project ID:MOST104-2321-B182-009-MY3