Mapping Successful PAH Treatments Using Blood Signatures

Mapping Successful PAH Treatments Using Blood Signatures

Blood SignaturesIn a perfect world, equivalent responses to treatments from patients with pulmonary hypertension would make all treatment outcomes predictable and highly effective. In reality, this is not the case. However, distinguishing subtypes of pulmonary arterial hypertension can at least improve treatment outcomes by better matching patients to treatments using genetic signatures interpreted from blood samples.

A recent investigation into creating a blood signature was undertaken by a group of researchers at Vanderbilt University School of Medicine in Tennessee with colleagues from Queen’s University in Kingston, Ontario, Canada, and University of Chicago in Illinois. The authors found “A Peripheral Blood Signature of Vasodilator-Responsive Pulmonary Arterial Hypertension,” which is also the title of the study, published online ahead of print on the Circulation journal’s website on October 31, 2014.

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Although both vasodilator responsive pulmonary arterial hypertension (VR-PAH) and non-responsive pulmonary arterial hypertension (VN-PAH) are forms of pulmonary arterial hypertension, the two result in different outcomes toward certain treatments. Patients with VR-PAH show a pronounced response to calcium channel blockers, increasing survival relative to survival for patients with VN-PAH.

Knowing there must be a reason behind the difference, the team of researchers collected peripheral blood from patients treated at Vanderbilt University. The team extracted genetic information from patients’ white blood cells. Twenty-five genes of interest allowed the creation of a decision tree used to identify VR-PAH. Results were validated by information obtained from genetic material of patients at the University of Chicago.

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Thirteen of the 25 genes tested showed significant differences between VR-PAH and VN-PAH. Seven decision trees were built based off the two most different genes: DSG2 and RHOQ. Both genes are involved in protein synthesis for cellular signaling pathways.

Five out of five VR-PAH patients were correctly identified at the University of Chicago. It should be noted VR-PAH accounts for a minority of pulmonary arterial hypertension cases.

These results can be applied in the clinic by extracting genetic information from a simple blood draw from patients with pulmonary hypertension. Using a decision tree based off the patient’s genetic signature could then indicate which treatments would most likely be successful.

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