Anti-U1 ribonucleoprotein (RNP) antibodies can be used as a potential risk factor for pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD), according to the results of a systematic review and meta-analysis published in the Journal of Clinical Medicine.

Recognizing that PAH is a common, serious complication of CTD, and that anti-U1 RNP antibodies could potentially indicate the development and prognosis of CTD-associated PAH (CTD-PAH), the researchers performed a systematic review and meta-analysis of the subject. CTDs are reported mainly in individuals with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS), and mixed connective tissue disease (MCTD).

The presence of anti-U1 RNP antibody was first observed among patients with MCTD, followed later by those with other CTDs, including SSc and SLE. Although CTD-PAH is associated with high rates of morbidity and mortality, early diagnosis of the disorder is difficult because of such nonspecific clinical symptoms as dyspnea, fatigue, and syncope. Oftentimes, the diagnosis of CTD-PAH is delayed, with severe right ventricular dysfunction already having developed by the time the disease has been identified.

Continue Reading

A total of 630 study results were identified via database searching. Following the removal of duplicates, the titles/abstracts of 476 studies were screened, with 423 of them excluded. Ultimately, 13 studies were included in the meta-analysis. These 13 studies involved a total of 6671 patients.

The majority of the patients were female, and most of the studies had been conducted in Asia. Overall, 3 studies involved SSc, 5 covered SLE, 2 concerned pSS, 1 involved myositis, and 2 studies covered multiple types of CTD.

Learn more about pulmonary arterial hypertension

Of the 13 studies selected for the meta-analysis, 10 contained statistics on the number of patients who were anti-U1 RNP antibody-positive in the CTD-PAH group and in the CTD-no PAH group. A random-effect model was adopted, as heterogeneity existed (P <.001). The pooled odds ratio was 5.30 (95% CI, 2.96-9.48; P <.001), which was indicative of anti-U1 RNP antibody-positivity as a risk factor for CTD-PAH.

Further, anti-U1 RNP antibody-positivity was also shown to be a protective factor against mortality among patients with CTD-PAH (hazard ratio, 0.55; 95% CI, 0.36-0.83; P = .005).

“To diagnose and treat PAH early, regular screening tests such as echocardiography are necessary for patients with anti-U1 RNP positive CTDs,” the authors concluded. “Anti-U1 RNP positivity was . . . proved to be associated with better survival in CTD-PAH. Further insight into the pathogenic role of the anti-U1 RNP antibody is needed, since anti-U1 RNP-positive patients may belong to a unique subset of CTD with a distinct phenotype.”


Xiang W, Dong R, Li M, Liu B, Ma Z, Yang Q. The role of anti-U1 RNP antibody in connective tissue disease-associated pulmonary arterial hypertension: a systematic review and meta-analysis. J Clin Med. 2023;12(1):13. doi:10.3390/jcm12010013