New centromere autoantigens identified in systemic sclerosis using centromere protein microarrays

Area of Science:

• Immunology
• Autoimmunity
• Proteomics

Background:

• Anticentromere antibodies (ACA) are key biomarkers in systemic sclerosis (SSc).
• Identifying novel ACA targets is crucial for understanding SSc pathogenesis and clinical associations.
• Centromere proteins (CENP) are primary targets of ACA.

Purpose of the Study:

• To discover new centromere protein (CENP) targets of anticentromere antibodies (ACA).
• To explore the clinical relevance of these novel ACA targets in systemic sclerosis (SSc).

Main Methods:

• Fabrication of a CENP-focused protein microarray with 14 purified CENP.
• Incubation of microarrays with SSc patient sera and healthy controls.
• Validation of newly identified CENP autoantigens using ELISA and Western blotting.

Main Results:

• Eleven CENP were identified as potential ACA targets in SSc patients.
• CENP-P and CENP-Q emerged as novel ACA autoantigens with high sensitivity in ACA-positive SSc sera.
• Anti-CENP-P antibodies were detected in ACA-negative SSc patients and correlated with renal disease; both anti-CENP-P and anti-CENP-Q showed prognostic utility for interstitial lung disease.

Conclusions:

• CENP-P and CENP-Q are validated as novel ACA autoantigens.
• Anti-CENP-P and anti-CENP-Q antibodies possess prognostic value for interstitial lung disease in SSc.
• Anti-CENP-P is associated with renal disease in ACA-negative SSc patients.