Triple-threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL-lpr mice

Area of Science:

• Immunology
• Proteomics
• Autoimmune Diseases

Background:

• Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies and immune complex deposition, particularly in the kidneys.
• The MRL-lpr mouse model is widely used for studying lupus and immune complex glomerulonephritis, yet its plasma proteome changes remain largely uncharacterized.

Purpose of the Study:

• To conduct in-depth quantitative proteome profiling of MRL-lpr mice and control (MpJ) mice.
• To investigate alterations in plasma proteome, immunoglobulins, their glycoproteome, and protein complexes in the MRL-lpr model.

Main Methods:

• Utilized immunohistochemistry, immunoglobulin isotyping, and multiplexed proteome profiling.
• Employed immunoglobulin immunoprecipitation with glycoproteome profiling and size exclusion chromatography (SEC).
• Applied a novel native multiplexed plasma proteome profiling (NativeMP3) method for ultra-deep single-shot profiling.

Main Results:

• Identified 922 plasma proteins at 1% FDR using the NativeMP3 method in a single mass spectrometry run.
• Observed substantial plasma protein differences between MRL-lpr and control mice.
• Detected significant alterations in immunoglobulins, antigen-specific antibodies, chemokines, proteases, and protein complexes like the immunoproteasome.

Conclusions:

• The study provides a comprehensive proteome profile of the MRL-lpr mouse model.
• Significant changes in plasma proteins and complexes offer insights into lupus pathogenesis.
• These findings may guide the development of novel diagnostic and therapeutic strategies for lupus.