Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

Area of Science:

• Immunology
• Rheumatology
• Genetics

Background:

• Type I interferon pathway activation is common in systemic lupus erythematosus (SLE).
• Anti-double-stranded DNA (anti-dsDNA) and anti-RNA binding protein (anti-RBP) autoantibodies correlate with high interferon-alpha (IFNα) activity in SLE patients.
• The association between antiphospholipid (APL) antibodies and IFNα activity is not well understood, particularly regarding their potential to stimulate Toll-like receptors.

Purpose of the Study:

• To investigate the association between antiphospholipid (APL) antibodies and high interferon-alpha (IFNα) activity in patients with systemic lupus erythematosus (SLE).
• To explore potential differences in this association across various ancestral backgrounds.

Main Methods:

• Serum IFNα activity was quantified in SLE patients using the WISH cell bioassay.
• Immunoglobulin G (IgG) APL, anti-RBP, and anti-dsDNA antibodies were measured using standard clinical laboratory methods.
• Positive antibody results were defined by established clinical cut-offs.

Main Results:

• High IFNα activity was associated with anti-RBP and anti-dsDNA antibodies across all studied ancestral groups.
• African-American subjects with positive IgG APL antibody tests exhibited significantly higher IFNα activity compared to those without.
• This association in African-Americans was independent of other autoantibody profiles and clinical features.

Conclusions:

• The distinct association between IFNα activity and IgG APL status in African-Americans suggests unique molecular pathogenesis in SLE.
• This finding may indicate B cell hyperactivity driven by type I interferon in this population.
• Understanding these differences could pave the way for individualized SLE treatment strategies.