Biomarkers Can Detect Scleroderma-linked PAH and Interstitial Lung Disease, Study Reports

Changes in gene expression occur early in scleroderma patients with pulmonary arterial hypertension or interstitial lung disease, which means that a collection of biomarkers can be used to detect these lung conditions early, a study reports.

The research dealt with what scientists call a biomarker panel for the conditions. The title of the article is “Patients with systemic sclerosis-associated pulmonary arterial hypertension express a genomic signature distinct from patients with interstitial lung disease.” It was published in the Journal of Scleroderma and Related Disorders.

Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are predictors of a worse outcome and death in patients with scleroderma, which is also known as systemic sclerosis, or SSc. Using biomarkers to detect the diseases early means doctors can begin treating them before they progress too far.

Previously, researchers developed a biomarker panel of 69 genes that were expressed differently — either increased or decreased — in SSc-PAH patients. They didn’t test the panel in SSc-ILD patients, however. Expression is the process by which a gene makes a functional product like a protein.

A group of scientists decided to use the biomarker panel to see whether SSc-ILD patients’ gene expression is different from SSc-PAH patients’.

They tested the panel using blood cells from 10 healthy individuals, 39 scleroderma patients, 21 patients with SSc-PAH, and 11 patients with SSC-ILD. The team defined SSc-ILD patients as those with evidence of fibrosis using a chest computed tomography scan and significant lung limitations.

When ILD patients were included in the cohort, four genes in the panel — S100P, CD8B1, CCL2, and TIMP1 — and male gender were accurate predictors of PAH.

When patients with ILD were excluded, two genes in the panel — THBS1 and CD8B1 — and male gender were accurate PAH predictors.

Based on these results, the researchers wrote that “SSc-PAH and SSc-ILD have similar but distinct gene expression profiles.”

Interestingly, SSc patients with borderline elevated pulmonary pressure — a sign of the beginning of PAH development — had a gene expression profile similar to that of patients with SSC-PAH, with the exception of THBS1. This suggested that changes in gene expression occur early in the course of the disease, giving doctors a chance at early detection.

In terms of the expression of specific genes, THBS1 expression was higher in patients with end-stage PAH than in controls. Mutations of the THBS1 gene have been reported in patients with familial PAH.

“THBS1 appears to be an important mediator in the development of pulmonary arterial hypertension-predominant phenotype,” the researchers wrote. “Further prospective investigation is warranted.”