Top-down Mass Spectrometry Analysis of Human Serum Autoantibody Antigen-Binding Fragments

Scientific Reports
Zhe WangSi Wu

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 th...Continue Reading

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Citations

May 3, 2019·Proteomics·Leah V SchafferLloyd M Smith
Nov 23, 2019·Journal of the American Society for Mass Spectrometry·Dahang YuSi Wu
Jan 15, 2020·Molecular Omics·Kellye A Cupp-Sutton, Si Wu
Mar 17, 2021·Journal of the American Society for Mass Spectrometry·Dahang YuSi Wu

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Methods Mentioned

BETA
ELISA
affinity purification
reversed phase liquid chromatography
ion-exchange chromatography

Software Mentioned

Deconv
ProteoWizard
Xcalibur
MS
msconvert
Velos Orbitrap Pro
miRAMM
TopPIC

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