Targeting rheumatoid arthritis biomarkers: High-abundance protein depletion by silicomolybdic acid-functionalized...

High-abundance proteins (HAPs) constitute more than 90% of total serum proteins, and their selective removal is crucial for improving the detection of low-abundance proteins that play key roles in disease mechanisms and potential biomarker discovery. In rheumatoid arthritis (RA), existing diagnostic potential biomarkers exhibit limited sensitivity and specificity, underscoring the need for more accurate molecular indicators. This study integrates HAPs depletion with advanced proteomic profiling to improve serum protein analysis and identify novel potential biomarkers associated with RA. A polyoxometalate-mosified metal-organic framework (POM-MOF) composite, SiMo₁₂O₄₀@UiO-66, was synthesized by immobilizing silicomolybdic acid (SiMo₁₂O₄₀) onto the UiO-66 framework via hydrogen bonding. The resulting oxygen-rich composite selectively adsorbs human serum albumin (HSA), transferrin (Trf), and immunoglobulin G (IgG) through electrostatic interactions with positively charged lysine and arginine residues. Under optimized experimental conditions (pH 5.0, 700 mmol·L^-1 NaCl, BR buffer), 1.0 mg of SiMo₁₂O₄₀@UiO-66 achieved removal efficiencies of 95.8% for HSA, 93.5% for Trf, and 75.0% for IgG from 1.0 mL of 100 μg·mL^-1 protein solutions. Adsorption kinetics and equilibrium data fitted well to the pseudo-first-order and Langmuir models, respectively, confirming monolayer adsorption behavior. Proteomic analysis using the application of liquid chromatography-mass spectrometry (LC-MS/MS) identified 203 proteins in untreated human serum and 214 proteins following HAP depletion, including 46 newly detected low-abundance proteins. Comparative proteomic profiling of RA and healthy sera revealed 154 differentially expressed proteins. Subsequent bioinformatics analysis highlighted five potential biomarkers, GAPDH, TPI1, PFN1, HSP90AA1, and CALM1, with CALM1 reported here for the first time in association with RA, indicating its potential diagnostic relevance.