Intracellular homocysteine metabolites in SLE: plasma S-adenosylhomocysteine correlates with coronary plaque burden

George Stojan, Jessica Li, Tian Liu, Maureen A Kane, Michelle A Petri
Lupus Science & Medicine 2021, 8 (1)

BACKGROUND AND AIMS: We hypothesised that intracellular homocysteine and homocysteine metabolite levels in patients with SLE are disproportionately elevated compared with the levels seen in healthy subjects and that they are independently associated with coronary plaque in SLE.

METHODS: A liquid chromatography-tandem mass spectrometry absolute quantification assay was used for the determination of six analytes in both plasma and peripheral blood mononuclear cells (PBMCs): homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), methionine (Met), cystathionine (Cysta) and 5-methyltetrahydrofolate (5m-THF). We then compared intracellular (PBMC) and extracellular (plasma) Hcy and Hcy metabolite (SAM, SAH, Met, Cysta and 5m-THF) concentrations in 10 patients with SLE and in 10 age, sex and ethnicity matched controls. Subjects with a history of diabetes mellitus, cardiovascular disease, hypertension, alcohol consumption in excess of 3 units per day, anaemia, renal insufficiency (serum creatinine >1.5 mg/dL) and pregnancy were excluded. All patients with SLE had two coronary CT angiography studies as screening for occult coronary atherosclerotic disease.

RESULTS: Plasma from patients with SLE had higher levels of Hcy (p<0.0001), SAH (p<0.05), SAM (p<0.001) and lower levels of Met (p<0.05) and Cysta (p<0.001) compared with controls. PBMC intracellular concentrations from patients with SLE had higher levels of Cysta (p<0.05), SAH (p<0.05), SAM (p<0.001) and lower levels of 5m-THF (p<0.001). Plasma SAH showed a positive correlation with total coronary plaque, calcified plaque and non-calcified plaque (p<0.05).

CONCLUSION: Intracellular concentrations of Hcy metabolites were significantly different between patients with SLE and controls, despite similar intracellular Hcy levels. Plasma SAH was positively correlated with total coronary plaque, calcified plaque and non-calcified plaque.

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