Evaluation of plasma alpha-1-antichymotrypsin as a marker for pulmonary Kaposi sarcoma

Individuals with AIDS and Kaposi sarcoma (AIDS-KS) with pulmonary involvement have high-risk of poor outcomes but diagnosis of pulmonary KS in low-resource settings is difficult. We aimed to discover plasma proteins that distinguish individuals with pulmonary KS from those without pulmonary involvement. SomaScan proteomics screen measured 7288 plasma proteins in 22 cases and 17 controls selected from 181 participants with HIV-1 and cutaneous KS who underwent bronchoscopy. Cases had KS in the lower respiratory tract by bronchoscopy. Controls had no KS lesions detected by bronchoscopy. Results of the proteomics screen were confirmed by ELISA measurement of plasma alpha-1-antichymotrypsin (SERPINA3) in 18 cases and 13 controls and in an additional 162 individuals with AIDS-KS who were not included in the case-control analysis. Proteomics identified 12 plasma proteins with differential levels in controls and cases. Plasma alpha-1-antichymotrypsin (SERPINA3) complex was consistently higher in cases compared to controls in the proteomics assay. Measurement of plasma alpha-1-antichymotrypsin by ELISA confirmed higher levels in cases (median 399.4, IQR 95.77-766.4 μg/ml) versus controls (median 39.98, IQR 31.2-170.2 μg/ml; p = .001). Plasma alpha-1-antichymotrypsin correlated with the estimated burden of pulmonary KS in the respiratory tract (r = 0.439; p = .0002) and 234 μg/ml had 51% sensitivity and 94% specificity for detection of pulmonary KS by bronchoscopy. Measurement of plasma alpha-1-antichymotrypsin has potential for identifying persons with pulmonary AIDS-KS and estimating the burden of KS in the lower respiratory tract.