Year: 2019
Type: article
Abstract: Detecting autoimmune diseases at an early stage is crucial for effective treatment and disease management to slow disease progression and prevent irreversible organ damage. In many autoimmune diseases, disease-specific autoantibodies are produced by B cells in response to soluble autoantigens due to defects in B cell tolerance mechanisms. Autoantibodies accrue early in disease development, and several are so disease-specific they serve as classification criteria. In this study, we established a high-throughput, sensitive, intact serum autoantibody analysis platform based on the optimization of a one dimensional ultra-high-pressure liquid chromatography top-down mass spectrometry platform (1D UPLC-TDMS). This approach has been successfully applied to a 12 standard monoclonal antibody antigen-binding fragment (Fab) mixture, demonstrating the feasibility to separate and sequence intact antibodies with high sequence coverage and high sensitivity. We then applied the optimized platform to characterize total serum antibody Fabs in a systemic lupus erythematosus (SLE) patient sample and compared it to healthy control samples. From this analysis, we show that the SLE sample has many dominant antibody Fab-related mass features unlike the healthy controls. To our knowledge, this is the first top-down demonstration of serum autoantibody pool analysis. Our proposed approach holds great promise for discovering novel serum autoantibody biomarkers that are of interest for diagnosis, prognosis, and tolerance induction, as well as improving our understanding of pathogenic autoimmune processes.
Source: Scientific Reports
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,790
Funders: U.S. Department of Health and Human Services, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Oklahoma Center for the Advancement of Science and Technology, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1067063329, G1139746577, G1428910847, Quantitative Analysis of Serum Autoantibody Repertories in Systemic Lupus Erythematosus, G2506161245, Defining the role of altered cytokine signaling pathways on autoimmunity, G4189806895, G4851551467, G582323035, G6380662341, Oklahoma Autoimmunity Center of Excellence Mechanisms of Disease Flare, Sequencing serum autoantibody biomarkers through an antigen-targeted top-down mass spectrometry (ATT-MS) platform, G7979596938, G8021174655, G8069432362, G8146145158, G9000006405, G9000149483, G9000150122, G9000210687
OpenAlex ID: W2918082626