Background: In rheumatoid arthritis (RA) patients, synovitis causes severe articular cartilage damage. N-acetylglucosamine (NAc-Glc) is a component of gluglucosaminoglycans (GAG) such as hyaluronic acid (HA) and keratan sulfate (KS), heparan sulfate (HS). NAc-Glc concentration in plasma is thought to reflect the balance between biosynthesis and destruction of articular cartilage, however, few studies had examined the relationship between plasma NAc-Glc conncentration and RA activity.

Objectives: NAc-Glc concentrations in RA patients were measured, and association with clinical indicators was assessed.

Methods: A cross-sectional study was carried out including 60 RA cases. Using N-acetylglucosamine-d3 as standard, the serum of subjects were deproteinized by protein precipitation method with acetonitrile, then concentration of NAc-Glc was measured with high-speed liquid chromatography mass spectrometer (LC-MS / MS). Clinical evaluation items: basic metabolism, presence or absence of exercise habit, Larsen score of knee and wrist joint, therapeutic agents (csDMARDs, biologics and PSL), DAS28, CRP, MMP-3, modified HAQ score (mHAQ). Statically analyzed by Spearman non parametric test.

Results: The age of 60 RA cases was 59.7±16.4 years, and the duration of the disease was 10.4±8.7 years. Biologics were used in 29 cases (TNF inhibitors in 16 cases, IL-6 inhibitors in 4 cases, Abatacept in 9 cases), MTX in 32 cases, and prednisolone in 15 cases.

Plasma NAc-Glc concentration was 113±41 (ng/dl), DAS28CRP was 3.04±1.2, and mHAQ was 0.863±891. Plasma NAc-Glc concentration showed positive correlation with age (correlation coefficient 0.644), knee joint destruction (0.425), HAQ score (0.340), BUN (0.412), and RF (0.287). Plasma NAc-Glc concentrations also negatively correlated with eGFR (-0.597), MTX use (-0.389), basal metabolism (-0.313), and sex difference (-0.272). There was no correlation between plasma NAc-Glc concentration and body weight, BMI, DAS28, CRP, MMP-3, NTX, serum creatinine, hand joint disease, and transaminase.In this study, plasma NAc-Glc concentration had increased with age, and had have a negative correlation with basal metabolism. Considering these results, it is unlikely that NAc-Glc is released into plasma as a metabolite of synthesis promotion. Further, since NAc-Glc had a negative correlation (-0.389) with MTX as a folic acid inhibitor, it was supposed to be affected by protein synthesis reduction. Because no correlation between NAc-Glc and inflammation or bone metabolism markers was observed, NAc-Glc may represent removal of GAG from the cell membrane (shedding).

In previous GAGs studies, in RA patients, HA, KS, CRP, DAS28, was very associated with arthritis, such as MMP-3.The concentration of NAc-Glc in plasma was more relevant to dysfunctions such as destruction and HAQ due to arthritis such as HAQ than inflammatory indicators such as DAS28, MMP-3 and CRP. It is appearing in the plasma by destruction by shedding, as an index to see the joint destruction, it was presumed to be a better indicator than the GAGs. It was also thought that there is a possibility that MTX affects cartilage substrate metabolism.

Conclusion: Serum NAc-Glc concentration in rheumatoid arthritis patients may represent cartilage metabolism and joint destruction.

REFERENCES:

[1]Y.Matsuura. et al.Ann.Rheum.Dis. 2018;77: 1219-1225

[2]T D Spector.et al. Ann.Rheum.Dis. 1992;51: 1134-1137

Disclosure of Interests: None declared