Anti-U3 RNP autoantibodies in systemic sclerosis

Area of Science:

• Rheumatology
• Immunology
• Systemic Autoimmune Diseases

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, vascular dysfunction, and immune dysregulation.
• Anti-U3 RNP autoantibodies are associated with specific clinical subsets of SSc, but their full impact on disease characteristics and survival requires further elucidation.

Purpose of the Study:

• To delineate the classification, demographic, and clinical features of SSc patients who are positive for anti-U3 RNP autoantibodies.
• To compare the survival rates between anti-U3 RNP autoantibody-positive and negative SSc patient cohorts.

Main Methods:

• Retrospective review of medical records for 108 anti-U3 RNP-positive and 2,471 anti-U3 RNP-negative SSc patients.
• Detection of anti-U3 RNP antibody using protein and RNA immunoprecipitation.
• Statistical comparison of disease features and survival using Student's t-test, chi-square analysis, and Mantel-Haenszel test.

Main Results:

• Anti-U3 RNP-positive SSc patients showed a higher prevalence of African American (27% vs 5%) and male (29% vs 19%) individuals, and were younger at diagnosis (mean age 42.8 vs 47.4 years).
• Increased frequency of skeletal muscle involvement (25% vs 14%) and pulmonary arterial hypertension (PAH) (31% vs 13%) was observed in the anti-U3 RNP-positive group.
• While diffuse cutaneous involvement was similar, skin scores were lower in anti-U3 RNP-positive patients. Survival was worse in the anti-U3 RNP-positive group (HR 1.38), with PAH being the primary cause of death (30% vs 10%).

Conclusions:

• Anti-U3 RNP autoantibodies in SSc are associated with a distinct demographic profile, including higher representation of African American and male patients, and younger age at diagnosis.
• SSc patients with anti-U3 RNP antibodies exhibit a higher burden of skeletal muscle involvement and PAH, with PAH significantly contributing to reduced survival.
• These findings highlight PAH as a critical determinant of mortality in anti-U3 RNP-positive SSc patients, underscoring the need for targeted monitoring and management strategies.