miRNAs as biomarkers in pneumonia and COPD-exacerbation

MicroRNAs (miRNAs) are small regulatory RNA molecules. Their dysregulation has been associated with many inflammation-mediated diseases. In recent years, miRNAs have been recognized as important post-transcriptional regulators of the innate immune response. Their property to be stable and detectable in almost all body fluids makes them attractive new biomarker candidates. Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. An abrupt onset of severe illness, the lack of identification of the relevant pathogenic agent in the majority of the episodes and the difficulty to distinguish CAP from other acute airway infections demonstrate the urgent need to find new diagnostic (and prognostic) tools.

In the present work, the miRNA profile of peripheral blood mononuclear cells (PBMCs) of CAP patients was assessed in a clinical pilot study and compared to patients suffering from acutely exacerbated chronic obstructive pulmonary disease (AE-COPD), a chronic pulmonary disease aggravated by an acute viral or bacterial infection. Receiver operation characteristic (ROC) analysis revealed single miRNAs to be sufficient to distinguish healthy controls from critically ill patients. Furthermore, by discriminant function analysis a panel of five miRNAs was found to discriminate between CAP, AE-COPD patients and healthy controls. In comparison with healthy controls, analysis of PBMCs of a first cohort of CAP and AE-COPD patients showed a significantly reduced expression of anti-inflammatory miR-146a. In the analyzed healthy controls relative expression of miR-146a correlates with age and inversely correlates with the absolute number of monocytes.

Taken together, PBMCs of CAP and AE-COPD patients show a very distinct miRNA expression pattern compared to healthy controls. ROC and discriminant function analysis revealed miRNAs as good candidates to discriminate between the two groups or between ill and healthy state, respectively.