Adipsin Protein Is a Biomarker of PAH Associated with Systemic Sclerosis, Study Finds

Adipsin Protein Is a Biomarker of PAH Associated with Systemic Sclerosis, Study Finds

Elevated levels of a protein called adipsin, produced by adipose or fat tissue, was found to be associated with an increased risk of pulmonary arterial hypertension (PAH) and associated cardiovascular deregulation in patients with systemic sclerosis (SSc).

The findings were reported in a report titled “Elevated Adipsin Levels are Associated with Pulmonary Arterial Hypertension in Systemic Sclerosis,” recently published in the scientific journal Arthritis & Rheumatology.

Caused by autoimmunity deregulation, vessels damage, and tissue fibrosis, systemic sclerosis (SSc) is a disease that can have different specific clinical presentations. This variability makes it harder to diagnose and manage the disease.

SSc is a condition that can affect several organs, including the lungs, which in turn can lead to the development of interstitial lung disease and pulmonary arterial hypertension (PAH). These pulmonary complications are associated with poorer prognosis and even death among patients with SSc.

As a result, it is essential to identify SSc-PAH biological markers that may detect those at risk and promote early diagnosis and prevention.

Adipose tissue is well-known for its capacity to produce and secrete molecules known as adipokines, which have the ability to regulate several biological mechanisms in the body. This also includes events associated with SSc development and progression, although how this happens is not fully understood.

To clarify this issue, researchers at the Feinberg School of Medicine at Northwestern University evaluated adipokine production in 198 patients with SSc, of whom 116 had limited cutaneous SSc (lcSSc) and 82 had diffuse cutaneous SSc (dcSSc), and compared it to that observed in 33 healthy people, or controls.

Researchers found that the levels of the adipokines adipsin and adiponectin were elevated in lcSSc patients compared to dcSSc and controls groups. The team then focused on a detailed analysis of adipsin involvement in SSc.

They observed that increased levels of adipsin were not associated with markers of fibrosis in SSc, but they were instead associated with a 3.3-times higher risk of developing SSc-PAH. This association was found to be even stronger and more specific than that observed with B-type natriuretic peptide (BNP) — a widely used biomarker for SSc-PAH.

“Patients with elevated adipsin levels were more likely to have the limited cutaneous form of SSc and were at significantly increased risk for PAH and related cardiac dysfunction,” the researchers wrote.

Analysis of adipsin gene expression in two independent cohorts confirmed that it was elevated in SSc-PH patients and was associated with pulmonary injury.

“Taken together, these findings suggest that elevated adipsin production may play a pathogenic role in SSc-PAH,” the team wrote.

This finding may open new therapeutic avenues for these patients. Treatments such as the investigative adipsin inhibitor lampalizumab developed by Roche — currently in a Phase 3 trial (NCT02247479) for macular degeneration (vision deterioration) — or Soliris (eculizumab), a complement inhibitor already approved for the treatment of rare red blood cells disorders, can become viable options for SSc-PAH patients.

“We identify adipsin as a novel adipose tissue-derived marker of PAH in SSc. Circulating adipsin levels might serve as predictive biomarkers in SSc,” the researchers concluded.

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