Proteomics

Pioneering Proteomics in Rheumatic Disease Research

In recent years, advances in proteomics and the analysis of large patient cohorts have improved the understanding of rheumatic diseases such as osteoarthritis and rheumatoid arthritis (RA). Our research has not only confirmed the presence of inflammation-related proteins such as S100 and SAA in the early 2000s^1,2, but has also uncovered new biomarkers that could change the way these diseases are diagnosed and monitored.

Innovative Biomarker Discovery in Osteoarthritis

Our team has identified specific peptides, including the complement factor C3f and a fragment of vitronectin, that are present in osteoarthritis³. Using nano-liquid chromatography on chip tandem mass spectrometry, we have developed a novel approach for the absolute quantification of these peptides⁴. This method allowed us to accurately measure the vitronectin fragment VTN_{(381-397 a.a.)} in serum samples of various rheumatic diseases⁵. Its biological role was also investigated (see section related to “fibrosis”).

Glycoprotein Research in Rheumatoid Arthritis

Our proteomic research has also focused on the glycosylation status of glycoproteins in the early stages of rheumatoid arthritis. We found that the glycosylation of key proteins such as corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP) is altered in RA. Remarkably, these changes can be reversed after one year of treatment⁶. This finding highlights the potential of glycoproteins as valuable biomarkers both for diagnosing RA and for monitoring treatment response.

Proteins associated with inflammation and ER stress in rheumatic diseases

We also used mass spectrometry (2D-nano-UPLC-ESI-Q-Orbitrap) to identify proteins involved in endoplasmic reticulum (ER) stress, inflammation and pannus formation in synovial biopsies from patients with osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis^7,8. These proteins were detected in all samples and showed a strong correlation with histological inflammatory scores, highlighting their critical role in synovial inflammation and immune cell infiltration.

Transforming diagnostics and treatment monitoring

Our ongoing research in proteomics is uncovering new biomarkers and providing deeper insights into the molecular mechanisms of rheumatic diseases. These discoveries not only improve our ability to diagnose OA and RA earlier, but also offer new ways to monitor treatment response, ultimately leading to more personalized and effective therapies.

 

References

Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach

de Seny D, Fillet M, Meuwis MA, Geurts P, Lutteri L, Ribbens C, Bours V, Wehenkel L, Piette J, Malaise M and Merville MP.
Arthritis Rheum. 2005, 52, 3801-3812.

Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis

de Seny D, Fillet M, Ribbens C, Maree R, Meuwis MA, Lutteri, L, Chapelle JP, Wehenkel L, Louis E, Merville MP and Malaise M.
Clin Chem. 2008, 54, 1066-1075.

Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis

de Seny D, Sharif M, Fillet M, Cobraiville G, Meuwis MA, Maree R, Hauzeur JP, Wehenkel L, Louis E, Merville MP, Kirwan J, Ribbens C, and Malaise M.
Ann Rheum Dis. 2011, 70, 1144-1152.

Validation of a new method by nano-liquid chromatography on chip tandem mass spectrometry for combined quantitation of C3f and the V65 vitronectin fragment as biomarkers of diagnosis and severity of osteoarthritis

Cobraiville G, Fillet M, Sharif M, Ourradi K, Nys G, Malaise MG, de Seny D.
Talanta. 2017, 169:170-180.

Modulation of α_Vβ₆ integrin in osteoarthritis synovitis and interaction with VTN_{(381-397 a.a.)} competing for TGF-β1 activation

Ciregia F, Deroyer C, Cobraiville G, Plener Z, Malaise O, Gillet P, Fillet M, Malaise MG, de Seny D.
Experimental & Molecular Medicine. 2021 53:210-222.

 Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

Ciregia F, Baiwir D, Cobraiville G, Dewael T, Mazzucchelli G, Badot V, Di Romana S, Sidiras P, Sokolova T, Durez P, Malaise MG, de Seny D.
J Transl Med. 2020, 18:8.

Proteins involved in the endoplasmic reticulum stress are modulated in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological inflammatory score

de Seny D, Bianchi E, Baiwir D, Cobraiville G, Collin C, Deliège M, Kaiser MJ, Mazzucchelli G, Hauzeur JP, Delvenne P, Malaise MG.
Sci Rep. 2020, 10:14159.

New Proteins Contributing to Immune Cell Infiltration and Pannus Formation of Synovial Membrane from Arthritis Diseases

de Seny D, Baiwir D, Bianchi E, Cobraiville G, Deroyer C, Poulet C, Malaise O, Paulissen G, Kaiser MJ, Hauzeur JP, Mazzucchelli G, Delvenne P, Malaise M.
Int J Mol Sci. 2021, 23:434.