Over One-third of Patients With Autoantibodies at Risk for PH: Study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Two doctors look surprised as they confer over a chart.

People with systemic scleroderma (SSc) who have certain autoantibodies are at increased risk of developing pulmonary hypertension, or high pressure in the blood vessels of the lungs, according to a study in the U.S.

Researchers also observed that patients who tested positive for these autoantibodies, called anti-Th/To antibodies, showed limited skin thickening — a common symptom of scleroderma.

“Patients presenting with limited skin involvement should be tested for [anti]-Th/To [antibodies],” the researchers wrote, adding that those positive for the autoantibodies should be closely monitored for the development of lung disease.

The study, “Over one-third of Th/To antibody positive scleroderma patients develop pulmonary hypertension in long-term follow-up,” was published in the journal Arthritis & Rheumatology.

People with SSc may have certain antibodies, called autoantibodies, directed against components of their own tissues. Some of these autoantibodies are linked to how the disease manifests and progresses over time.

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shortened survival found with pulmonary hypertension/Scleroderma News/lungs illustration

Pulmonary Hypertension in SSc Patients Found to Shorten Survival

In previous work, the researchers found that about 4% of patients with SSc tested positive for anti-Th/To antibodies, which target two RNA-processing enzymes. Also, in a comparison with scleroderma patients with anticentromere antibodies, the team found that almost all of those with anti-Th/To antibodies had limited scleroderma, a form that is generally milder than diffuse scleroderma.

However, these patients often developed interstitial lung disease — a group of more than 200 types of lung diseases — and pulmonary arterial hypertension (PAH), which is caused by narrowing of the arteries that carry blood from the heart to the lungs. 

Now, the researchers took a further look into how the disease manifests and progresses in the presence of anti-Th/To antibodies. Their study involved 204 patients with SSc who went for a first visit to the Pittsburgh Scleroderma Center, in Pennsylvania, between 1980 and 2015.

All had tested positive for anti-Th/To antibodies with the use of immunoprecipitation, a technique that can pull down and detect a protein out of a solution. As controls, there were 408 patients with SSc who were negative for anti-Th/To antibodies. About three-quarters of all patients were women. The mean age of the anti-Th/To participants was 52.6 years, while that of the controls was 51.8.

The proportion of prior or current smokers was significantly higher among patients with anti-Th/To antibodies than among controls (64% vs. 44%), as was median disease duration (7.9 vs. 3.3 years).

At the initial visit, nearly all patients (97%) with anti-Th/To antibodies had limited skin thickening. They experienced Raynaud’s phenomenon, which occurs when fingers and toes feel numb and prickly under cold or stress, as a first symptom more often than controls (80% vs. 56%). In contrast, they had less frequent muscle, joint, and tendon involvement.

Imaging evidence of interstitial lung disease was more common in participants with anti-Th/To antibodies than in controls (45% vs. 34%), a difference sustained after a median follow-up of 6.1 years (54% vs. 39%).

When the researchers looked at the proportion of patients who had pulmonary hypertension at the initial visit, they found it was significantly higher among those with anti-Th/To antibodies than among controls (25% vs. 9%). This proportion rose to 38% versus 15% at follow-up.

The most common type of pulmonary hypertension was PAH, which occurred in 17% of the Th/To group versus 5% of controls at the initial visit, and in 23% versus 9% at follow-up. 

After accounting for age and sex, the researchers found that the presence of anti-Th/To antibodies increased the risk of developing pulmonary hypertension by 3.3 times at 10 years after the initial visit, and that of PAH by 4.9 times.

“These findings are relevant, as testing of the [anti]-Th/To [antibodies] using immunoprecipitation, as we have done here, is now commercially available,” the researchers wrote.

At the last follow-up visit, a similar proportion of patients had died in the two groups (56% in the Th/To group vs. 55% of controls).