SSc Patients with PAH Show High Levels of Adipsin in the Blood, Study Reports

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Systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) show high serum levels of adipsin, a peptide secreted from adipose tissue. Researchers believe adipsin could be used as a potential biomarker for SSc-PAH in these people.

The finding was reported in the study, “Elevated Adipsin Levels are Associated with Pulmonary Arterial Hypertension in Systemic Sclerosis,” published in the journal Arthritis & Rheumatology.

In SSc patients, adipose tissue beneath the skin, or subcutaneous white fat, is replaced by fibrotic tissue. Because adipose tissue synthesizes specific peptides known as adipokines, SSc patients’ adipokine levels are altered.

Adipokines — leptin, adiponectin, resistin, visfatin, and adipsin — regulate central processes, such as immune cell activation, vascular function, and fibrogenesis (fibrosis development). Therefore, adipokine levels may be associated with clinical features of SSc, and help to predict disease outcomes.

Researchers focused their work on adipsin, which they knew from previous work was present at higher than normal levels in people with limited cutaneous SSc (lcSSc) and PAH. They collected blood from 198 patients — 116 had lcSSc and 82 had diffuse cutaneous SSc (dcSSc) — and from 33 healthy individuals who served as controls. They then measure the serum levels of adipsin.

The team found that adipsin levels were substantially increased in people with lcSSc, particularly those with PAH. Among the lcSSc patients, 25.8% had high levels of adipsin, compared with 1.2% of people with dcSSc, and 6.1% of those in the control group.

Patients with high adipsin levels also showed a significant higher risk for pulmonary hypertension, and a reduction in a measure called diffusion of lung carbon monoxide (DLCO), a reflection of lung disease severity. (DLCO measures how much oxygen travels from the alveoli, or small air sacs, of the lungs to the blood stream.)

These patients also had a higher risk of heart anomalies; namely, right ventricular dysfunction and diastolic dysfunction.

Researchers then searched available datasets and found that lcSSc patients with PAH or increased PAH susceptibility had certain adipsin gene variants, which were associated with increased adipsin levels.

Due to the strong correlation observed between adipsin levels and disease, they suggest that adipsin levels work as a new marker of SSc-PAH progression.

Besides being a disease biomarker important for predicting disease and its progression, they wrote, adipsin may also have therapeutic value.

Adipsin seems to activate the complement cascade, an immunological process overactive in SSc patients but unexplored so far for its therapeutic value.  “Adipsin and complement cascade activation represent potential drug targets,” the team concluded.