French Team Links Certain Antibodies to Improved Survival of PAH Patients with Lupus

French scientists have identified antibodies that appear to increase the risk of a poor outcome in pulmonary arterial hypertension patients with lupus and others they believe improve patients’ survival.

Anti-SSA/SSB antibodies are a risk factor in PAH patients with systemic lupus erythematosus, or SLE, while anti-U1-RNP antibodies are associated with a better survival rate.

The research, “Pulmonary Arterial Hypertension Associated with Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry,” was published in the journal Chest.

PAH associated with connective tissue disease (PAH-CTD) is the second most prevalent cause of pulmonary hypertension after idiopathic/heritable PAH. Conversely, lupus is the second most common cause of PAH-CTD after systemic sclerosis.

PAH occurs in less than 4 percent of SLE patients, with PAH being diagnosed by the gold standard —  right heart catheterization (RHC). In using echocardiography to diagnose PAH in SLE patients, different studies found no cases of SLE-PAH. Due to this low prevalence, systematic screening for PAH in SLE patients is currently not recommended by the European Society of Cardiology and the European Respiratory Society.

Study of the SLE-PAH association is hampered by few case series (a descriptive type of study that samples patients with a specific disease) in medical research. Moreover, SLE-PAH series with PAH diagnosed by RHC are even rarer.

Researchers decided to assess all SLE-PAH patients enrolled in the French Pulmonary Hypertension Registry between June 2003 and June 2013. PAH diagnosis was confirmed by RHC. A group of 101 SLE patients without known PAH, but who had undergone echocardiography, were used as controls. The analysis focused on characteristics and survival rates of patients.

From a total of 69 SLE-PAH patients, 51 met the inclusion criteria. These patients did not differ from the control group in age, sex, or duration of SLE at the time of data collection.

Results showed that the mean delay between diagnoses of SLE and PAH was 4.9 years, with the range being 2.8-12.9 years. In half of the patients, PAH was diagnosed within the first five years after SLE diagnosis. In seven cases, the diagnosis was done within one year.

The three- and five-year overall survival rates after PAH diagnosis were 89.4% and 83.9%, respectively.

Cyclophosphamide was the most common treatment for PAH in the cohort analyzed. Furthermore, a trend for better survival was observed in patients receiving the anti-SLE drug hydroxychloroquine at or in the months following PAH diagnosis.

Interestingly, SLE-PAH patients were found to have a higher frequency of the anti-SSA and anti-SSB antibodies associated with autoimmune diseases such as SLE. Other identified risk factors for PAH development were kidney involvement and higher pulmonary vascular resistance.

In contrast, anti-U1-RNP antibodies were found to be associated with an improved survival rate. The presence of these antibodies is known in patients with SLE and also in those with CTD.

A total of 11 patients died during the 10-year follow-up period. Nine died of cardiopulmonary complications, whereas two of infection. No patients out of 14 with anti-U1-RNP antibodies died during the 10-year follow-up. In contrast, six deaths were reported out of 24 patients in the group without anti-U1-RNP.

“Anti-SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti-U1-RNP antibodies appears to be a protective factor regarding survival,” the researchers wrote.

Nonetheless, the team emphasized that further studies are needed to confirm the results.