Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue diseases (CTDs) and is associated with significant morbidity and mortality. Among multiple prognostic factors in systemic sclerosis (SSc)-associated PAH, most research has focused on hemodynamics and clinically determined exercise tolerance (New York Heart Association functional class and 6-minute walk test). However, diagnosis of CTD also involves laboratory testing, particularly levels of the antibody to the U1 ribonucleoprotein complex (anti-U1RNP).
To investigate the clinical characteristics and survival rates of patients who were anti-U1RNP positive with CTD-associated PAH, Vincent Sobanski, MD, and colleagues studied the Royal Free Hospital PH database, which prospectively included patients who underwent at least 1 right-sided heart catheterization (RHC) between January 1, 1998 and December 31, 2012 and demonstrated the standard hemodynamic parameters for RHC.
PAH was defined as a mean pulmonary arterial pressure ≥25 mm Hg by RHC at rest without raised cardiac output. Information on autoimmune serology was obtained retrospectively from database review or chart records. Antinuclear antibody serologies (anti-topoisomerase I, anti-U1 RNP, anti-SSA/Ro, anti-SSB/La, and anti-Jo-1 antibodies) were also obtained. Survival data were retrieved from clinical records or the UK NHS database (data were censored at March 1, 2013 for analysis).
Of 2250 patients who underwent RHC for suspected PAH, 1013 were diagnosed previously as having a CTD (SSc, systemic lupus erythematosus, or mixed CTD). Among them, 342 CTD patients had PAH. Of these particular patients with CTD-associated PAH, 36 (11%) were anti-U1 RNP antibody positive. Analysis showed that anti-U1 RNP-positive patients were younger and less functionally impaired than anti-U1 RNP-negative patients with CTD- associated PAH. Hemodynamic parameters were similar in anti-U1 RNP-positive and anti-U1 RNP-negative patients.
The 3- and 5-year survival rates from the time of PAH diagnosis were 63% and 43%, respectively, for SSc-associated PAH; 86% and 85%, respectively, for SLE-associated PAH; and 100% and 100%, respectively, for mixed CTD-associated PAH (P < .001). Thirty-six of 342 patients with CTD-associated PAH (11%) had anti-U1 RNP antibodies: 14 with SSc, 10 with SLE, 2 with overlapping SSc and SLE, and 10 with mixed CTD.
Thus, it appeared that survival was significantly different between the CTDs (SSc, SLE, and mixed CTD) associated with PAH. In the population of patients with CTD-associated PAH, anti-U1 RNP positivity was associated with several unique clinical characteristics and had an improved survival rate in univariable and multivariable analysis.
Summary and Clinical Applicabilty
This study found that survival differs between SSc-, SLE-, and mixed CTD-associated PAH, and that anti-U1 RNP-positive serology was associated with increased survival in CTD-associated PAH. This study was limited by the population examined, as it was conducted at a single PAH referral center, which may limit generalizability. The retrospective design of the study also restricted the scope of the data collection, including specific immunosuppressive therapies, occurrence of particular clinical symptoms pointing to worsened prognosis, or detailed CTD organ involvement.
Sobanski V, Giovannelli J, Lynch BM, et al. Characteristics and survival of anti-U1 RNP-antibody-positive patients with connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheumatol. 2016;68(2):484-493.