TY - JOUR
T1 - Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics
AU - Tang, Chenling
AU - Fang, Min
AU - Tan, Gongjun
AU - Zhang, Shu
AU - Yang, Bowen
AU - Li, Yaxi
AU - Zhang, Ting
AU - Saxena, Ramesh
AU - Mohan, Chandra
AU - Wu, Tianfu
N1 - Publisher Copyright:
Copyright © 2022 Tang, Fang, Tan, Zhang, Yang, Li, Zhang, Saxena, Mohan and Wu.
PY - 2022/3/24
Y1 - 2022/3/24
N2 - Objective: The goal is to discover novel circulating immune complexes (ICx) in the serum of lupus nephritis (LN) as potential biomarkers. Methods: Protein A/G magnetic beads or C1q-coated plates were used to capture ICx in the serum of LN, followed by the identification of immunoglobulin-binding proteins using liquid chromatography and tandem mass spectrometry (LC-MS/MS). Bioinformatic approaches and single-cell RNA sequencing (scRNA Seq) databases were used to select potential candidate ICx markers in LN. The selected ICx markers were further validated using ELISA. Results: A total of 300 immunoglobulin-binding proteins were discovered in the screening, among which 77 proteins were detectable only in LN samples. Bioinformatics-assisted selection allowed us to further identify 10 potential immunoglobulin-binding proteins, which form ICx as potential biomarkers in LN. In a validation cohort of 62 LN patients and 21 healthy controls (HC), we found that prolyl 3-hydroxylase 1 (P3H1), phosphatase and actin regulator 4 (PHACTR4), and regulator of G-protein signaling 12 (RGS12) ICx exhibited discriminative capability in distinguishing LN from HC, with an area under the curve (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.
AB - Objective: The goal is to discover novel circulating immune complexes (ICx) in the serum of lupus nephritis (LN) as potential biomarkers. Methods: Protein A/G magnetic beads or C1q-coated plates were used to capture ICx in the serum of LN, followed by the identification of immunoglobulin-binding proteins using liquid chromatography and tandem mass spectrometry (LC-MS/MS). Bioinformatic approaches and single-cell RNA sequencing (scRNA Seq) databases were used to select potential candidate ICx markers in LN. The selected ICx markers were further validated using ELISA. Results: A total of 300 immunoglobulin-binding proteins were discovered in the screening, among which 77 proteins were detectable only in LN samples. Bioinformatics-assisted selection allowed us to further identify 10 potential immunoglobulin-binding proteins, which form ICx as potential biomarkers in LN. In a validation cohort of 62 LN patients and 21 healthy controls (HC), we found that prolyl 3-hydroxylase 1 (P3H1), phosphatase and actin regulator 4 (PHACTR4), and regulator of G-protein signaling 12 (RGS12) ICx exhibited discriminative capability in distinguishing LN from HC, with an area under the curve (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.
KW - biomarker panel
KW - biomarkers
KW - immune complex (ICx)
KW - immunoproteomics
KW - lupus nephritis
KW - systemic lupus erythematosus
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U2 - 10.3389/fimmu.2022.850015
DO - 10.3389/fimmu.2022.850015
M3 - Article
C2 - 35419005
AN - SCOPUS:85128287655
SN - 1664-3224
VL - 13
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 850015
ER -