Searching for new biomarkers in SSc-associated PAH

There are interesting proteins that could be used as biomarkers in people with PAH associated with systemic sclerosis


Systemic sclerosis (SSc) is an autoimmune disease that causes abnormalities in the skin, joints, and internal organs, including the lungs. It is associated with changes in blood vessels and with scarring or thickening in affected tissues, such as the skin and lungs. Systemic sclerosis is more common in women than men, and most often develops between the ages of 30–50 years.

A major complication of systemic sclerosis is high blood pressure in the vessels that supply the lungs. This is called pulmonary arterial hypertension (PAH), and it is one of the leading causes of death in people with systemic sclerosis. At present, PAH can be diagnosed only by performing an invasive procedure called a right-heart catheterisation (RHC), where a tube is inserted into the heart to measure the pressure. This is done via a vein in the arm. RHC is also used to assess the severity of PAH, and to evaluate a person’s response to treatment.

What did the authors hope to find?

The authors hoped to identify proteins in people’s blood that could serve as markers for PAH severity. Finding something like this would help reduce the number of people who need to undergo RHC, as well as the number of repeat RHC examinations in people with PAH. They also hoped that the identified protein could tell us more about the underlying biological mechanisms that cause the disease.

Who was studied?

The study looked at several different groups of people, who participated in three different parts at different times. This included people with systemic sclerosis with and without PAH, as well as controls without systemic sclerosis from the general population. 

How was the study conducted?

In part 1 of the study, blood samples from the different groups were tested for more than 1,000 proteins in order to identify those that correlated best with PAH severity. This was called the discovery group

These proteins were then validated in another group of people to see if they met the same criteria as in the original discovery group. 

Finally, follow-up experiments were done on lung samples from people who had undergone a lung transplant because of interstitial lung disease associated with their systemic sclerosis. 

What was the main finding?

The main finding was that a protein called chemerin is strongly correlated with PAH severity. The experiments also suggest that this protein contributes to the development of PAH in people with systemic sclerosis by increasing the number of blood vessel cells.

Are these findings new?

To the author’s knowledge, until now very few studies have focused on identifying proteins that reflect PAH severity. Although previous studies have identified chemerin as being involved in various vascular diseases (notably in another type of PAH called idiopathic PAH), this is the first study to suggest that this protein could also be involved in the development of PAH associated with systemic sclerosis.  

What are the limitations of this study?

One possible limitation is that these results will not be found or be able to be replicated in other groups of people with systemic sclerosis and PAH. This is because both these diseases can be very variable in how they affect people. This study used a very limited group of people to look at, which might mean the findings cannot be generalised to other people.   

There are also some limitations with the statistical methods used, which means that some biomarkers could have been missed. 

Finally, because of the small sample size and missing data, it was not possible to assess the added value of chemerin serum levels as part of a diagnostic tool or risk assessment for people with PAH. 

What do the authors plan to do with this information?

The authors are currently planning to study how chemerin could be used in patient management. For instance whether changes in levels of this protein reflect changes in the need to perform RHC.

What does this mean for me?

If you have systemic sclerosis, you might need to undergo RHC. This is essential to diagnose and assess PAH, and to help make sure you get the right treatment. But these results could mean that in the future there might be other less invasive options for these assessments. 

If you have any questions about your disease or its treatment, speak to your healthcare team. 

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Date prepared: July 2023
Summary based on research article published on: February 10, 2023
From:Summary from Sanges S, et al. Biomarkers of haemodynamic severity of systemic sclerosis-associated
pulmonary arterial hypertension by serum proteome analysis. Ann Rheum Dis 2023;82(3):365–73.

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