Biosignatures Distinguish Between Fatal Lung Diseases

In the blood of tuberculosis and sarcoidosis patients a complete gene and micro-ribonucleic acid (miRNA) expression profiles have been created together with important inflammatory mediators.

It is almost impossible to distinguish between tuberculosis (TB) and sarcoidosis with just a single signature, therefore a set of different biosignatures is better suited for distinguishing between diseased and healthy individuals and, in a further step, between the specific diseases.

Scientists at the Max Planck Institute for Infection Biology (Berlin, Germany) using gene and miRNA expression in blood cells and inflammatory mediators in serum, selected sets of markers characteristic for tuberculosis and sarcoidosis patients. Although both diseases primarily damage the lungs and produce similar symptoms, they have very different causes as TB is caused by an infection with the bacteria Mycobacterium tuberculosis, while sarcoidosis is not contagious.

The two diseases are not only similar clinically but their biosignatures have a number of elements in common. Compared to healthy individuals, most genes in sarcoidosis and tuberculosis patients are regulated in a similar way. The results obtained by the Berlin investigators show that modified biomarkers can be traced back to processes that occur not only in one specific disease, such as immune responses. The immune response therefore draws on the same basic elements in different clinical pictures, and only a few of these elements are specific to a particular disease. These commonalities also reveal to scientists a lot about the general causes and mechanisms underlying many diseases.

In total, around 150 miRNAs shared by both diseases differed from healthy individuals. Only four miRNAs are suitable for distinguishing TB and sarcoidosis patients. The overlap is less pronounced in the profile of inflammatory substances in the blood: while only one of these cytokines is modified equally in TB and sarcoidosis compared to healthy individuals, twelve of these signal mediators are suitable for distinguishing between the two diseases.

A single biosignature is therefore not enough to distinguish between healthy and diseased individuals, and to distinguish between different diseases with a similar clinical phenotype. Although the combination of many genes increases specificity and sensitivity in distinguishing between healthy and diseased individuals, it automatically leads to a lower specificity compared to other clinical pictures.

Stefan H.E. Kaufmann, PhD, a professor at the Max Planck Institute, said, "Of approximately 13,000 genes whose expression differs, depending on whether the individual is healthy or diseased, approximately 9,000 genes are expressed in the same way in both diseases. Only 700 genes differ in their expression between tuberculosis and sarcoidosis patients - but these can be used to unequivocally identify the two diseases."

Related Links:
Max Planck Institute for Infection Biology