Kynurenine pathway is altered in patients with SLE and associated with severe fatigue, 2018, Akesson et al.

J

Jaybee00

Senior Member (Voting Rights)
https://lupus.bmj.com/content/5/1/e000254


Conclusions Metabolites in the kynurenine pathway are altered in patients with SLE compared with controls. Interestingly, fatigue correlated weakly with measures of enhanced tryptophan metabolism, while depression did not. Drugs targeting enzymes in the kynurenine pathway, for example, IDO inhibitors or niacin (B12) supplementation, which suppresses IDO activity, merit further investigation as treatments in SLE.
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The B12 = niacin error jumped out at me too. :) What was missing from the abstract is that they only measured serum and urine levels of metabolites. Since central fatigue is neurological, and many kynurenines don't cross the BBB easily, I consider their findings to be fairly useless. If they'd measured CSF levels, they might have gotten some interesting results. ME might involved fairly localized alterations in glial activity and kynurenine levels, so even a spinal tap may not reveal ME's secrets. I think some method of brain scanning for kynurenines may be needed.
 
Full abstract
Objective Fatigue has been reported as the most disturbing symptom in a majority of patients with SLE. Depression is common and often severe. Together these symptoms cause significant morbidity and affect patients with otherwise relatively mild disease. Tryptophan and its metabolites in the kynurenine pathway are known to be important in several psychiatric conditions, for example, depression, which are often also associated with fatigue. We therefore investigated the kynurenine pathway in patients with SLE and controls.

Methods In a cross-sectional design plasma samples from 132 well-characterised patients with SLE and 30 age-matched and gender-matched population-based controls were analysed by liquid chromatography tandem mass spectrometry to measure the levels of tryptophan and its metabolites kynurenine and quinolinic acid. Fatigue was measured with Fatigue Severity Scale and depression with Hospital Anxiety and Depression Scale. SLE disease activity was assessed with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Results The kynurenine/tryptophan ratio, as a measure of indoleamine 2,3-dioxygenase (IDO) activity, was increased in patients with SLE. Patients with active disease (SLEDAI ≥6) showed lower tryptophan levels compared with controls (54 µM, SD=19 vs 62 µM, SD=14, p=0.03), although patients with SLE overall did not differ compared with controls. Patients with SLE had higher levels of tryptophan metabolites kynurenine (966 nM, SD=530) and quinolinic acid (546 nM, SD=480) compared with controls (kynurenine: 712 nM, SD=230, p=0.0001; quinolinic acid: 380 nM, SD=150, p=0.001). Kynurenine, quinolinic acid and the kynurenine/tryptophan ratio correlated weakly with severe fatigue (rs =0.34, rs =0.28 and rs =0.24, respectively) but not with depression.

Conclusions Metabolites in the kynurenine pathway are altered in patients with SLE compared with controls. Interestingly, fatigue correlated weakly with measures of enhanced tryptophan metabolism, while depression did not. Drugs targeting enzymes in the kynurenine pathway, for example, IDO inhibitors or niacin (B12) supplementation, which suppresses IDO activity, merit further investigation as treatments in SLE.
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Kynurenine again! It's interesting how there was once a theory of too much serotonin causing fatigue in ME, and now it's an imbalance in the tryptophan/kynurenine pathway (both in ME and SLE).

It's like the elephant in a dark room. Someone's feeling the trunk and thinks it's a snake. Maybe gradually, we can work out how all the bits fit together.
 
adambeyoncelowe said:
Kynurenine again! It's interesting how there was once a theory of too much serotonin causing fatigue in ME, and now it's an imbalance in the tryptophan/kynurenine pathway (both in ME and SLE).

It's like the elephant in a dark room. Someone's feeling the trunk and thinks it's a snake. Maybe gradually, we can work out how all the bits fit together.
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after 4 years in bed 100% I wish I was the elephant ...
 
adambeyoncelowe said:
Kynurenine again! It's interesting how there was once a theory of too much serotonin causing fatigue in ME, and now it's an imbalance in the tryptophan/kynurenine pathway (both in ME and SLE).
Click to expand...

It's interesting they appear to suggest that increased circulating levels of kynurenine could be linked to central fatigue, when the OMF trial is exploring the possibility of supplementing it...the objectives of the two studies may be different, though (I'm way out of my depth!)
 
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