Serum Proteomics Identified the Association of Haptoglobin and Orosomucoid 1 with Disease Activity in Takayasu Arteritis.

Background: Takayasu arteritis (TAK) is a chronic granulomatous vasculitis, and accurate early diagnosis and assessment of disease activity remain significant clinical challenge. Traditional biomarkers such as CRP and ESR have insufficient sensitivity and specificity. High-throughput proteomics provides a robust method for discovering new biomarkers for TAK. Methods: A comparative serum proteomic analysis of 8 TAK patients and 9 healthy controls (HCs) was conducted using mass spectrometry. Bioinformatic analyses were performed on differentially expressed proteins (DEPs). Candidate biomarkers were prioritized through machine learning and correlation analyses. An independent validation cohort with 51 TAK patients and 31 HCs was used to confirm the biomarkers using ELISA. The correlations were assessed between the new biomarkers and the clinical parameters as well as disease activity scores. Results: We identified 88 DEPs between TAK patients and HCs. Pathway analysis revealed enrichment in phagosome, platelet activation, and inflammatory response. Among these, Haptoglobin (HP) and Orosomucoid 1 (ORM1) were selected as top candidate biomarkers based on their high feature importance scores and strong correlation with inflammatory markers. ELISA validation confirmed that serum levels of HP and ORM1 were significantly elevated in TAK patients compared with HCs, and further increased in active TAK compared with stable TAK patients. Both biomarkers showed significant positive correlations with clinical inflammatory indicators (ESR, FIB, WBC) and immune cell counts, as well as disease activity scores. Conclusion: Our integrated proteomic analysis identified HP and ORM1 as 2 novel serum biomarkers significantly associated with disease activity, inflammatory and immune processes in TAK.