Racial variability in immune responses only partially explains differential systemic sclerosis disease severity

Area of Science:

• Rheumatology
• Immunology
• Genetics

Background:

• Systemic sclerosis (SSc) exhibits significant racial variations in disease severity and clinical manifestations.
• Understanding the role of autoantibodies in these disparities is crucial for targeted treatment strategies.

Purpose of the Study:

• To investigate the association between race, autoantibody profiles, and clinical outcomes in a large cohort of Black and White patients with SSc.
• To determine the extent to which autoantibodies mediate the observed racial differences in SSc severity.

Main Methods:

• Systematic autoantibody testing (Euroimmun and ELISA) in 803 Black and 2178 White SSc patients.
• Logistic regression analysis to assess the association between race and outcomes, adjusting for autoantibodies.
• Comparison of race coefficients in models with and without autoantibodies to evaluate mediation effects.

Main Results:

• Distinct autoantibody profiles were observed: anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku, and anti-NOR90 were more prevalent in Black patients, while ACA, anti-POLR3, and anti-PM/Scl were enriched in White patients.
• Black patients showed a higher prevalence of severe Raynaud's phenomenon, skin, lung, gastrointestinal, and renal disease.
• White patients had a higher prevalence of severe heart and muscle disease.
• Adjusting for autoantibodies partially explained racial differences in certain outcomes (e.g., lung, gastrointestinal disease) but increased the association between race and renal crisis.

Conclusions:

• Black and White individuals with SSc possess distinct autoantibody profiles.
• Autoantibodies account for only a portion of the racial disparities in SSc clinical outcomes.
• Other unidentified factors likely contribute significantly to the observed differences in disease severity and progression between racial groups.