Proteome profiling of Cryoglobulinemia

ObjectiveTo better understand and identify candidate protein biomarkers of cryoglobulinemia (CGE) from healthy patients or benign brain disease control patients. MethodsThe tandem mass tag (TMT)-labeled quantitative proteomics approach was used to identify differential proteins in the serum proteome of 10 CGE patients and 10 disease control patients with negative cryoglobulin (CG), respectively. GO, KEGG and protein domain enrichment analysis was used for functional annotation of differential proteins. The biomarker candidates were validated by the parallel reaction monitoring (PRM) method in 20 samples (10 CGE patients, 5 healthy control patients, and 5 disease control patients). ResultsA total of 1004 proteins were quantitatively identified. Among these, 62 proteins were upregulated, and 56 proteins were downregulated. 25 candidate biomarkers were validated by PRM. 5 upregulated proteins of A2M, MMP2, VCAM1, MCAM, and PCSK9, and 4 downregulated proteins of C3, IGHG2, PROZ, PPBP were consistent with TMT results. Upregulated proteins mostly related with cholesterol metabolism, while downregulated proteins were associated with immune regulation. ConclusionThis study is the first proteomic study of cryoglobulinemia in China These findings might contribute to the application of proteomics for detecting and monitoring CGE. And our findings indicated cholesterol metabolism accelerates the development of CGE.