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Anti-RNP and anti-Sm antibodies are risk factors for pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE), according to a meta-analysis by Chinese researchers.

The finding supports that transthoracic echocardiography should be "routinely performed" in SLE patients with these risk factors, Xiaofeng Zeng, MD, of Peking Union Medical College in Beijing, and colleagues wrote in .

The risk of death for patients with SLE-associated PAH is far greater than that of the SLE population at large, with pooled 5-year survival rates of 68% and 94.8%, respectively, the team noted. PAH is an independent risk factor for mortality. Although early recognition of PAH followed by prompt and intensive treatment may improve functional status and survival, "early recognition is difficult because PAH is often silent and patients may not exhibit specific cardiopulmonary symptoms until they are already in the advanced stages."

Further, PAH development and severity with SLE duration or disease activity, Zeng et al continued. "The high mortality and the imperceptible clinical symptoms of PAH prompt the need for reliable markers to detect early or even predict this cardiopulmonary complication."

Prior studies of antibodies associated with PAH in SLE yielded conflicting results. The authors therefore conducted a meta-analysis to search for potential serologic biomarkers in SLE-associated PAH.

Twelve observational studies were included, most of which enrolled Asian patients. Studies ranged in size from 51 participants to more than 1,900. The mean age of participants in the studies ranged from 26.5 to 47.8 years. In the largest study, mean SLE duration was 3.4 years, and the mean pulmonary arterial systolic pressure was 54.2 mm Hg.

The following autoantibodies and their relation to PAH were examined: anti-RNP, anti-Sm, anti-dsDNA, anti-SSA, anti-SSB -- all autoantibodies that would be tested routinely in patients with SLE.

Anti-RNP antibody was the strongest predictor for the development of PAH, with a pooled odds ratio (OR) of 3.68 (95% CI 2.04-6.63, P<0.0001), the researchers reported. The pooled OR for anti-Sm antibody was 1.71 (95% CI 1.06-2.76, P=0.03).

This is the first known report of an association between anti-Sm antibody and development of PAH, the authors said. "Anti-Sm has been thought of as the marked antibody of SLE, which generally remains positive, even when a patient has entered remission. Therefore, it can be a stable predictor as it will not fluctuate along the disease activity, which is different from anti-dsDNA."

The pooled ORs for anti-dsDNA, anti-SSA, and anti-SSB antibodies, were 1.23 (95% CI 0.85=1.79, P=0.28); 1.17 (95% CI 0.53-2.57, P=0.70); and 1.16 (95% CI 0.82-1.65, P=0.40), respectively -- none of which reached statistical significance, the researchers said.

They uncovered strong evidence of heterogeneity in the ORs for anti-RNP, anti-dsDNA, anti-Sm, and anti-SSA (I2=81%, 53%, 57%, and 85%, respectively). A funnel plot did not show evidence of publication bias.

Further analysis of subgroups based on study type, ethnicity, background, sample size, method to confirm PAH, classification criteria, and other causes of PAH was conducted. The OR for the development of PAH was strengthened to 2.10 (95% CI 1.42-3.12, P=0.0002) in the subgroup of patients with anti-dsDNA antibody who underwent right heart catheterization as the method to confirm PAH. Among SLE patients with PAH confirmed by right heart catheterization, the pooled OR for anti-RNP antibody reached 10.56 (95% CI 2.50-20.28, P<0.00001).

In other studies, anti-RNP antibody "showed a considerable positive rate among SLE–PAH patients (16.2-86.7%)," the investigators wrote. "Anti-RNP antibody was also considered to be the predictor of vascular lesions in SLE and a risk factor for PAH associated with connective tissue diseases, especially ." Although the underlying mechanism is not fully understood, "we assumed this antibody may be involved in the common pathway of vasculopathy, which contributes to the development of PAH," the researchers said.

They noted that a limitation is the small sample of studies included in the meta-analysis and the focus on an Asian population, limiting the generalizability of the findings. Another concern is the lack of a strict set of definitions to diagnose PAH. Finally, most of the studies included were case-control or cross-sectional.