Scleroderma-Specific Autoantibodies in Early Systemic Sclerosis Save

Prognostication is tenous in early scleroderma, especially in those with diffuse cutaneous systemic sclerosis (dcSSc). dcSSc has associated with substantial morbidity and disease-specific mortality. Analysis of an early SSc registry shows that anti-RNA polymerase III autoantibodies in early SSc were associated a higher risk of worse phenotypes and clinical outcomes.

While Scleroderma-specific autoantibodies (SSc-Ab) are thought to influence disease course, but their prognostic value in very early dcSSc remains unclear.  This study was a retrospective analysis of prospectively collected data from a subset of patients enrolled in an early SSc registry (October 2012 and July 2021) - this included early dcSSc or individuals at risk for dcSSc (< 2 yrs of their first non-Raynaud phenomenon (RP) symptom).  SSc-Abs included: anti-RNA polymerase III antibody positive (RNAP3+), anti-topoisomerase I antibody positive (Scl70+), or triple-negative (negative for RNAP3, Scl70, and anticentromere antibody [ACA]).

Cohort included 115 patients with a median follow-up, 5.5 years -- 42 were RNAP3+, 29 Scl70+, 38 triple-negative, and 6 ACA+ (these were excluded from subgroup due to small sample size). 

Clinical Course Associations (92 patients). 

• About half (54%) experienced new clinical events (60%  RNAP3+, 57% Scl70+, 47% of triple-negative patients).
• RNAP3+ patients had higher frequencies of:
  • scleroderma renal crisis (6.3% vs 3.6% in Scl70+ and 0% in triple-negative)
  • malignancy (35.7% vs 24.1% and 15.8%, respectively)
  • mortality (9.4% vs 3.6% and 0%, respectively)
  • FVC decline (15.6% vs 10.7% and 12.5%, respectively)
• modified Rodnan skin score worsening was most frequent in triple-negative patients (15.6% vs 10.7% in Scl70+ and 9.4% in RNAP3+).

Scleroderma-specific autoantibodies in early SSc were associated with distinct baseline clinical phenotypes and showed numerical differences in longitudinal clinical outcomes in this single-center cohort.