To confirm this, we performed a bioinformatics analysis to determine which proteins may be involved in the disease course of SLE or LN and may?potentially serve as a disease biomarker

To confirm this, we performed a bioinformatics analysis to determine which proteins may be involved in the disease course of SLE or LN and may?potentially serve as a disease biomarker. that prolyl 3-hydroxylase 1 (P3H1), phosphatase and actin regulator 4 (PHACTR4), Rabbit Polyclonal to IKK-gamma and regulator of G-protein signaling 12 (RGS12) ICx exhibited discriminative capability in distinguishing LN from HC, with Salvianolic acid F an area Salvianolic acid F under the curve Salvianolic acid F (AUC) values of 0.82, 0.99, and 0.90, respectively. Furthermore, a biomarker panel comprising CD14, CD34, cystatin A, myocyte enhancer factor 2C (MEF2C), RGS12, and ubiquitin C (UBC) ICx could distinguish active LN from inactive LN with an AUC value of 0.85, which is comparable to or better than pathological parameters such as renal activity index (AI) and renal chronicity index (CI). Conclusion Immunoproteomics-based discovery studies have enabled us to identify circulating immune complexes as potential biomarkers of LN. Keywords: immunoproteomics, immune complex (ICx), biomarkers, biomarker panel, systemic lupus erythematosus, lupus nephritis Introduction Systemic lupus erythematosus (SLE) is usually a multifactorial and heterogeneous autoimmune disease, manifested by autoantibody production and altered type I interferon expression and regulation (1C3). About 60% of SLE patients are eventually advanced into potentially fatal lupus nephritis (LN) (4, 5). LN is usually a leading cause of mortality in SLE patients, and the treatment of LN has become a significant interpersonal and economic burden in the United States (6). Unfortunately, the diagnosis or disease monitoring of SLE or LN is usually suboptimal. The current gold standard for clinical diagnosis of LN is usually renal biopsy, which is usually invasive and may cause kidney damage (7, 8). Using serum for any liquid biopsy is usually minimally invasive; therefore, serum biomarkers may have great potential in the diagnosis and disease monitoring of LN patients in clinical settings. Given the heterogenetic nature and unmet needs in precision diagnosis and classification of SLE/LN patients for personalized medication, identification of novel biomarkers, particularly in the form of a biomarker panel, is usually of paramount importance (9). Omics studies are encouraging in the discovery of novel serum biomarkers which may aid in accurate diagnosis and disease monitoring of LN clinically (10, 11). Robust serum biomarkers may also be useful in developing point-of-care systems that can be used for home screening of LN. IgG antinuclear autoantibodies (ANA) against components such as DNA and nucleoprotein are commonly found in the glomeruli and serum of individuals with LN (12). The etiology of LN entails antibody binding to multiple autoantigens (AAgs) (13). Through the FcCFcR conversation, the intracellular or extracellular AAgs can bind to specific autoantibodies to form immune complexes (ICx), which as a double-edged sword may exert pathological effects or beneficial regulatory effects, depending on the antigenCantibody ratio, antibody subclass, and antigen subcellular location (14, 15). Therefore, disease-associated ICx, particularly AAgs, may not only contribute to the pathogenesis of the disease but also serve as disease biomarkers in autoimmune diseases such as SLE and LN. Omics technologies, such as genomics, transcriptomics, proteomics, and metabolomics, are rapidly evolving which enable the discovery of putative biomarkers in SLE (16). In particular, single-cell RNA sequencing (scRNA Seq) allows us to investigate transcriptomic profiles at a single-cell resolution, in which the function of rare cell populations and the information on communication among different cell types can lengthen our understanding of the Salvianolic acid F pathogenesis and heterogeneity of SLE (17). A single-cell analysis of intrinsic renal cells and infiltrating cells from patients with LN may be helpful in defining the pathways of renal injury.