Inflammation
Serum Amyloid A (A-SAA) – Beyond a Biomarker
A-SAA is one of the most prominent acute-phase proteins whose concentration in blood is highly increased during the acute phase response (APR) of inflammation. It has been long considered as a biomarker of inflammatory diseases but over time this role has been gradually overcome. Nowadays, A-SAA is rather considered as a non-specific marker heavily expressed during inflammation. However, our work has uncovered that several SAA variants are differentially modulated across various rheumatic conditions, such as rheumatoid arthritis (RA), systemic sclerosis, systemic lupus erythematosus, and ankylosing spondylitis. This suggests that each SAA variant may have a distinct pathophysiological role, warranting further investigation into their specific biological functions.
Innovative Proteomics for A-SAA variants analysis
Prof. M. Fillet from LAM, ULiège, Belgium, in collaboration with our team developed an advanced method using targeted bottom-up proteomics (LC-MS/MS) to accurately quantify several SAA variants1. This technique has enabled us to identify both quantitative and qualitative differences in SAA variants among osteoarthritis (OA) and other inflammatory diseases, such as rheumatoid arthritis (RA), systemic sclerosis, systemic lupus erythematosus, and ankylosing spondylitis. For example, variants like SAA1α and SAA2α show variable expression depending on the disease, whereas others, like SAA1γ and SAA2β, remain constant. These findings underscore the significance of studying individual SAA variants for a more nuanced understanding of disease mechanisms.
Insights from Early Rheumatoid Arthritis (ERA)
Our recent studies on early RA (ERA) have revealed that specific SAA variants, particularly SAA1α and SAA2α, are elevated in ERA patients and correlate with clinical parameters2. This indicates that different SAA variants may play unique roles in disease progression, offering potential pathways for targeted therapeutic strategies.
Exploring Inflammation in the Synovial Membrane
In addition to our work on A-SAA, we have been investigating the inflammatory processes within the synovial membrane in OA. Using proteomic analysis, we identified proteins involved in endoplasmic reticulum (ER) stress, inflammation, and pannus formation in synovial biopsies from OA, chronic pyrophosphate arthropathy (CPPA), and RA patients3,4. These proteins were detected in all samples and their expression levels were strongly correlated with histological inflammatory scores, indicating their important role in synovial inflammation and immune cell infiltration.
Driving Future Research
Our research continues to uncover the molecular basis of inflammation in OA and other rheumatic diseases, paving the way for improved diagnostic markers and targeted treatments.
References
Nys G, Cobraiville G, Servais AC, Malaise MG, de Seny D*, Fillet M*.
Talanta. 2019, 204:507-517.
Ciregia F, Nys G, Cobraiville G, Badot V, Di Romana S, Sidiras P, Sokolova T, Durez P, Fillet M, Malaise MG, de Seny D.
Front Immunol. 2021, 12:638814.
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.
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.
