Dataset Information

Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics

ABSTRACT: The goal is to discover novel circulating immune complexes (ICx) in the serum of Lupus Nephritis (LN) as potential biomarkers. 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). Six related genomic-level databases were used for selecting potential biomarkers, following ELISA validation with independent samples.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Lupus Nephritis

SUBMITTER: chenling tang

LAB HEAD: Tianfu Wu

PROVIDER: PXD031069 | Pride | 2022-05-20

REPOSITORIES: Pride

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Publications

Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics.

Tang Chenling C Fang Min M Tan Gongjun G Zhang Shu S Yang Bowen B Li Yaxi Y Zhang Ting T Saxena Ramesh R Mohan Chandra C Wu Tianfu T

Frontiers in immunology 20220324

<h4>Objective</h4>The goal is to discover novel circulating immune complexes (ICx) in the serum of lupus nephritis (LN) as potential biomarkers.<h4>Methods</h4>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 cand ...[more]

PMID: 35419005

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Project description:Introduction: Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. Methods: We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n=45) to healthy controls (n=17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n=23) and without significant renal involvement (n=18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n=23) and longitudinal samples (88 patient visits) to test its accuracy. Results: Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B-cell activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV & X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative nephritis with 91% accuracy. Conclusions: Autoantigen microarrays are an ideal platform for identifying autoantibodies associated with both pSLE and specific clinical manifestations of pSLE. Using multiple regression analysis to integrate autoantibody and clinical data permits accurate prediction of clinical manifestations with complex etiologies in pSLE.

Dataset Information

Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics

Publications

Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics.

Similar Datasets

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