LC-MS/MS Proteomics for Rheumatoid Arthritis Biomarker Discovery

A research team comprised of staff associated with Shenyang Medical College, Liaoning Vocational College of Medicine, and the College of Sciences of Northeastern University (all in Shenyang, China) integrated high-abundance proteins (HAPs) depletion with advanced proteomic profiling to improve serum protein analysis and identify novel potential biomarkers associated with rheumatoid arthritis (RA). 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. A paper based on this research was published in the Journal of Colloid and Interface Science.¹

A chronic systemic autoimmune disorder typified primarily by continuing inflammation of the joints and surrounding connective tissues, RA affects approximately 0.5–1% of the worldwide adult population.^2-4 While it can arise at any age, occurrences of RA increase greatly after the age of 40, with women being two to three times more likely to be affected than men.^5,6

In this study, SiMo₁₂O₄₀ was successfully immobilized onto the surface of the metal-organic framework UiO-66 through hydrogen bonding, resulting in the formation of a novel composite material, SiMo₁₂O₄₀@UiO-66. Owing to its favorable electrostatic interactions, the composite exhibited high efficiency in adsorbing and depleting abundant serum proteins, including the three most abundant proteins in human blood plasma—human serum albumin (HSA), transferrin (Trf), and immunoglobulin G (IgG).^1,7

“This work,” write the authors of the paper,¹ “introduces an innovative strategy for the selective removal of HAPs from human serum. Furthermore, coupling this depletion method with MS and bioinformatics analysis enabled comprehensive differential proteomic profiling of sera from healthy controls and RA patients. Through this approach, five potential RA-associated potential biomarkers, GAPDH, TPI1, PFN1, HSP90AA1, and CALM1, were identified, offering valuable insights into RA pathogenesis and advancing prospects for its early diagnosis and targeted therapeutic research.”

“The integrated solid phase extraction (SPE)-LC-MS/MS platform,” the authors continue,¹ “not only offers a powerful tool for early RA diagnosis and mechanistic insight but also presents a versatile approach for potential biomarker discovery across diverse pathological conditions, with promising implications for clinical diagnostics, precision medicine, and personalized therapeutic development.”

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References

1. Wang, Y.; Wu, S.; Zhu, Q. et al. Targeting Rheumatoid Arthritis Biomarkers: High-Abundance Protein Depletion by Silicomolybdic Acid-Functionalized Metal-Organic Frameworks. J Colloid Interface Sci. 2026, 711, 140080. DOI: 10.1016/j.jcis.2026.140080
2. Khojakulova, U.; Yessirkepov, M.; Zimba, O. et al. Massage Therapy in Rheumatoid Arthritis. Rheumatol. Int.2025, 45, 76. DOI: 10.1007/s00296-025-05833-3
3. Y. Suda, Y.; K. Ikuta, K.; S. Hayashi, S. et al. Comparison of Anti-Inflammatory and Anti-Angiogenic Effects of JAK Inhibitors in IL-6 and TNFα-Stimulated Fibroblast-Like Synoviocytes Derived from Patients with RA. Sci. Rep.2025, 15, 9736. DOI: 10.1038/s41598-025-94894-2
4. Finckh, A.; Gilbert, B.; Hodkinson, B. et al. Global Epidemiology of Rheumatoid Arthritis. Nat. Rev. Rheumatol.2022, 18, 591-692. DOI: 10.1038/s41584-022-00827-y
5. I.C. Scott, I. C.; R. Whittle, R.; J. Bailey, J.et al. Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis Epidemiology in England from 2004 to 2020: An Observational Study Using Primary Care Electronic Health Record Data. Lancet Reg. Health - Eur. 2022, 23, 100519. DOI: 10.1016/j.lanepe.2022.100519
6. I.E. Christensen, I. E.; S. Lillegraven, S.; P. Mielnik, P. Serious Infections in Patients with Rheumatoid Arthritis and Psoriatic Arthritis Treated with Tumour Necrosis Factor Inhibitors: Data from Register Linkage of the NOR-DMARD Study. Ann. Rheum. Dis.2022, 81, 398-401. DOI: 10.1136/annrheumdis-2021-221007
7. Klooster, R.; Maassen, B. T.; Stam, J. C. et al. Improved Anti-IgG and HSA Affinity Ligands: Clinical Application of VHH Antibody Technology. J Immunol Methods 2007, 324 (1-2), 1-12. DOI: 10.1016/j.jim.2007.04.005