Research Study Identifies Two Proteins as Potential Biomarkers of SSc-PAH

Alice Melão, MSc avatar

by Alice Melão, MSc |

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FSTL3 MDK Midkine

Evaluation of Midkine (MDK) and Follistatin-like 3 (FSTL3) protein levels in the blood can help identify patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH), researchers suggest.

The study, “Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis” was published in the journal Arthritis Research & Therapy.

Systemic sclerosis (SSc), also known as scleroderma, is a progressive autoimmune disorder characterized by the accumulation of collagen in the skin, making it harder and thicker. Collagen deposits can also affect other organs, including the kidneys, heart, intestinal tract, and lungs.

Involvement of the heart and lungs can severely compromise a patient’s chance of survival. It is estimated that about 12% of these patients develop SSc-PAH.

Currently, diagnosis of PAH relies on the invasive method of right heart catheterization (RHC). Still, this is only performed on patients with a high suspicion of PAH based on other less sensitive diagnostic methods.

As PAH diagnosis remains a clinical challenge, it becomes crucial to find new, reliable biomarkers that can support the prompt identification and treatment of patients at risk. To do this, a team led by Boston University researchers conducted a large-scale protein screening.

The team collected blood samples from 13 patients with confirmed limited cutaneous systemic sclerosis (lcSSc) with evidence of interstitial lung disease, and 16 patients with lcSSc without lung involvement. They analyzed the samples by the SOMAScan method, which can evaluate the levels of 129 proteins simultaneously.

Researchers identified 82 proteins that were significantly different between the two groups of patients. Of these proteins, 32 were increased and 50 were decreased on lcSSc-PAH patients.

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Many of the proteins were found to be related to immune cells’ response activation as well as regulation of extracellular tissue’s structural components. Sixteen of the identified proteins had already been detected in other studies in skin and lung tissue or blood cells of SSc-PAH patients.

Further analysis revealed that two proteins — MDK and FSTL3 —could help differentiate SSc patients with and without PAH.

Levels of the two proteins were found to be significantly higher in the lcSSc-PAH population compared with healthy volunteers, patients with diffuse cutaneous SSc, or lcSSc without lung involvement, and in patients with lcSSc with other interstitial lung diseases.

By analyzing the levels of MDK and FSTL3 in other two independent groups of lcSSc patients, the team could identify 85% to 92% of lcSSc-PAH cases.

“We showed that the combination of FSTL3 and MDK are highly associated for SSc-PAH, with an average sensitivity of 84% and an average specificity of 79%,” they said.

Based on the results, the team believes that the “combination of Midkine and FSTL3 can serve as an SSc-PAH biomarker and are potential drug targets for this rare disease population.”

Additional studies are warranted to further evaluate the potential of these and other proteins “to improve the diagnosis, care, and outcomes in this clinically challenging PAH subset,” the researchers said.