Abstract: SA-PO289

Anti-Ro Antibodies: A Novel Scleroderma Renal Crisis Biomarker

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Gordon, Sarah M., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Olson, Stephen W., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Background

Autoimmunity is thought to play a significant role in the pathogenesis of scleroderma renal crisis (SRC). Anti- RNA polymerase III (RNAPOL3-Ab) is associated with SRC but only present in 20—50% of cases. Therefore, additional autoimmune risk factors for SRC are likely. Anti-Ro antibodies (Ro-Ab) are known to be associated with systemic sclerosis (SSc), but have not been studied at or before SRC diagnosis.

Methods

We queried the military electronic medical record for ICD9 code 701.1 (SSc) between 2005 and 2016. By individual chart review we identified 54 SRC cases and 407 SSc without SRC disease controls. Background data was collected to include presence of Ro-Ab. Department of Defense Serum Repository (DoDSR) provided up to 3 longitudinal prediagnostic serum samples for 16 SRC cases and 30 age, sex, race, and age of serum matched SSc without SRC disease controls. Ro-Ab levels were measured at the NIH using an established luciferase technique. We first compared presence of Ro-Ab among the 54 SRC cases to the 407 SSc without SRC controls at SSc diagnosis. We then compared longitudinal pre-diagnostic Ro-Ab levels in 16 SRC cases to that of 30 SSc matched disease controls. The non-white group was predominantly Black or ‘Other.’

Results

More SRC cases had Ro-Ab at diagnosis than SSc without SRC disease controls (27% vs.13%, p=0.03). Ro-Ab were only associated with SRC in the non-White subgroup (38% vs.17%, p=0.04) versus the White subgroup (15% vs. 10%, p=0.69). More non-White SRC cases had persistent significantly elevated prediagnostic Ro-Ab than non-White SSc without SRC controls (40% vs.6%, p=0.01). In each SRC case, the Ro-Ab was greater than 30 times normal in the earliest available index sample up to 26.1 years before clinical presentation. No White cases had an elevated prediagnostic Ro-Ab level. Prediagnostic Ro-Ab and RNAPOL3-Ab were not present in the same cases.

Conclusion

We report for the first time that Ro-Ab are elevated both at and before SRC diagnosis, making it a potential predictive biomarker in non-Whites. Elevated serial prediagnostic Ro-Ab levels found decades before clinical SRC suggest a ‘multi-hit’ mechanism of disease that requires a second insult to manifest clinical disease. Our results also suggest that the subclinical pathophysiology of SRC may vary by race, similar to known clinical and serologic heterogeneity in SSc.

Funding

  • Other NIH Support