Interleukin-32 Shows Potential as Early Biomarker for PAH in Scleroderma Patients

A protein called interleukin-32 may serve as a biomarker for pulmonary arterial hypertension (PAH) in scleroderma patients, for whom PAH is a severe complication.

The study reporting the findings, “Interleukin-32 in systemic sclerosis, a potential new biomarker for pulmonary arterial hypertension,” was published in the journal Arthritis Research and Therapy.

Systemic sclerosis, also called systemic scleroderma (SSc), is an autoimmune disease characterized by the buildup of scar tissue in the skin and several internal organs, including the arteries. Cardiopulmonary involvement in the disease is the most common cause of mortality among SSc patients.

Survival rates for SSc patients who develop PAH (SSc-PAH) range from 50–81% within the first year of diagnosis, making early detection vital.

No specific biomarker for PAH has yet been identified, although many have been explored. Interleukin-32 (IL-32) — a pro-inflammatory cytokine (small proteins important in cell signaling) — surfaced as a candidate biomarker, because it is thought to regulate many of the activities of endothelial cells that line the pulmonary artery. Moreover, IL-32 is known to be activated in damaged vascular cells.

Researchers at the University of L’Aquila, in Italy, analyzed whether IL-32 could be a new biomarker of PAH in SSc patients.

The team tested the serum (blood) levels of 18 SSc-PAH patients, 21 SSc patients without PAH, 15 patients with idiopathic PAH (iPAH, meaning that the cause of PAH is unknown) and 14 healthy controls.

Serum levels of IL-32 were significantly higher in SSc-PAH patients than in any of the other groups — 99.9 picograms per milliliter (pg/ml). In fact, IL-32 was nearly undetectable in SSc patients without PAH, as well as in healthy controls. In the iPAH group, the mean levels of IL-32 were of 62.1 pg/ml.

IL-32 levels also correlated strongly with other measures of PAH, such as mean and systolic pulmonary arterial pressure (mPAP and sPAP, respectively), as measured by both right heart catheterization (RHC) and Doppler echocardiography, an ultrasound technique.

RHC is a standard and reliable means of diagnosing PAH, but also is highly invasive, consisting of inserting a long tube (catheter) into the pulmonary artery.

Researchers also found increased IL-32 levels in various skin cells of SSc patients with PAH, compared with those without PAH. In the case of one particular subset of SSc, called diffuse cutaneous SSc, the presence of these cells correlated with the modified Rodnan skin score (mRSS), a key measure of skin thickness used in evaluating SSc.

Further analysis suggested that a cut-off value of 11.12 pg/ml for IL-32 could predict patients with PAH.

Researchers concluded the results “suggested that sera determination of IL-32 may be a promising approach to evaluate the presence of PAH in SSc patients and together with longitudinal future studies could help to increase the understanding how these biomarkers mirror the vascular changes and the inflammatory process during SSc.”