The Long-Term Outcomes of Pulmonary Hypertension in Systemic Lupus Erythematosus (SLE-PAH) Vary Among Different Autoantibody-Based Clusters: An Observational, Longitudinal Study Conducted at a Single Centre in India

TL;DR

This study shows that SLE patients with pulmonary hypertension have different outcomes based on their autoantibody profiles, with some clusters responding better to treatment.

Contribution

The first study to use cluster analysis to classify SLE-PAH patients and link autoantibody profiles to treatment outcomes and mortality.

Findings

Sm-RNP positive patients (Cluster 1) had higher right ventricular systolic pressure and required more aggressive therapy.

Cluster 3 patients with multiple autoantibodies showed significant improvement in PAH after stopping anti-PAH therapy.

Aggressive anti-PAH therapy was associated with lower mortality, while nephritis and positive dsDNA correlated with higher mortality.

Abstract

Pulmonary arterial hypertension (PAH) is often overlooked in systemic lupus erythematosus (SLE) patients. However, the association between SLE and PAH is gaining attention due to unique mechanisms and treatment responses.

This study aims to categorise SLE-PAH patients by autoantibody profiles and evaluate long-term outcomes, including mortality and changes in PAH over 12 months.

A hospital-based investigation included SLE patients diagnosed with PAH. We analysed mortality, PAH resolution, increases in anti-PAH therapy, and follow-up right ventricular systolic pressure (RVSP) over 12 months. K-means cluster analysis was used for clustering, with regression analyses predicting mortality.

Analysing 111 SLE PAH patients revealed three clusters: Cluster 1 (CL1)—Sm-RNP positive (n=48), Cluster 2 (CL2)—no specific autoantibodies (n=36), and Cluster 3 (CL3)—multiple autoantibody positivity (n=27) (Smith, Sm-RNP, nucleosome, histone). Nephritis was significant in CL3 with multiple antibody positivity compared to CL1 and CL2 (p=0.01). CL1 showed a higher baseline mean RVSP (64.5 ± 19.1 (CL1) vs 57.5 ± 12.6 (CL2) vs 50.9 ± 12, p=0.002) and more frequent use of dual anti-PAH therapy (p=0.000). CL2, without any specific antibody, had an earlier onset of PAH (p=0.04). Significant improvement in PAH after withdrawing anti-PAH medication was noted in Cluster 3 (p=0.00). Regression analysis showed that aggressive anti-PAH therapy lowers PAH-related mortality (p=0.01), while nephritis (p=0.012) and positive dsDNA (p=0.009) correlate with higher mortality.

This study is the first to analyse SLE-PAH through cluster-based methods. Sm-RNP antibodies indicate more severe disease needing dual therapy, while multiple positive antibodies suggest a better prognosis, with most patients achieving PAH resolution.