Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2021, Simonato et al

Abstract
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease.

Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls.

Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease.

Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection.

Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS.

https://www.mdpi.com/2227-9059/9/11/1724

 

They found some genetic abnormalities in a few patients:

CASQ1 gene mutation with abnormal muscle biopsy
15q13.3 duplication (340 BP)
Ehlers–Danlos syndrome
Myotonia congenita

Should we think of these as separate disease in addition to ME/CFS, as contributing to ME/CFS, or as indicator that the ME/CFS diagnosis was not correct? We don't really know how to interpret this, right?

 

I guess it's potentially different for every individual? ME's not that uncommon, so it wouldn't be surprising if people had that diagnosis in addition to others, but I suppose some presentations of some other conditions could be confused with it. Especially if the diagnostic process had been undertaken at a stage where the patient had unclear symptoms, and then just got left on file.

Probably wouldn't confuse myotonia congenita with anything else, though, unless it affects people very differently. A boy in our class had it, and it was fairly visible.

 

Right. Lots of these kinds of things are indicative, but require further research to tell us how they fit in.

 

"There is generally little correlation between the position of a mutation in the channel and the phenotype. Indeed, identical sodium channel mutations in unrelated subjects and sometimes in different members of the same family can have different clinical expressions."
https://pubmed.ncbi.nlm.nih.gov/7735894/

The question is whether these muscle ion channel disorders could express themselves in a way that looks like ME/CFS and less like an obvious muscle disorder.

There is also another possibility: these muscle ion channels are not exclusively found in muscles but also in lower concentrarion in the nervous system. There, they might have effects that have not been discovered yet.

Something that is also suspicious is that severe ME/CFS is associated with episodes of paralysis which can be caused by an ion channel dysfunction.

 

I'm convinced that ME is neurological, so I don't expect serum studies to reveal much other than some downstream effects.