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

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.
Source: Manuela Simonato, Stefano Dall’Acqua, Caterina Zilli, Stefania Sut, Romano Tenconi, Nicoletta Gallo, Paolo Sfriso, Leonardo Sartori, Francesco Cavallin, Ugo Fiocco, Paola Cogo, Paolo Agostinis, Anna Aldovini, Daniela Bruttomesso, Renzo Marcolongo, Stefano Comai, and Aldo Baritussio. Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomedicines 2021, 9(11), 1724; https://doi.org/10.3390/biomedicines9111724 (registering DOI) https://www.mdpi.com/2227-9059/9/11/1724/htm (Full text)

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

Abstract:

BACKGROUND: As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively.

METHODS: Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection.

RESULTS: Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls.

CONCLUSION: These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

 

Source: Broderick G, Katz BZ, Fernandes H, Fletcher MA, Klimas N, Smith FA, O’Gorman MR, Vernon SD, Taylor R. Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue. J Transl Med. 2012 Sep 13;10:191. doi: 10.1186/1479-5876-10-191. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480896/ (Full article)

 

A gene signature for post-infectious chronic fatigue syndrome

Abstract:

BACKGROUND: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition.

METHODS: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7).

RESULTS: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance.

CONCLUSION: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment.

 

Source: Gow JW, Hagan S, Herzyk P, Cannon C, Behan PO, Chaudhuri A. A gene signature for post-infectious chronic fatigue syndrome. BMC Med Genomics. 2009 Jun 25;2:38. doi: 10.1186/1755-8794-2-38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716361/ (Full article)

 

Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan

Abstract:

In order to clarify the epidemiological features of chronic fatigue syndrome (CFS), a nationwide survey was conducted using the Japanese version of the CDC Criteria prepared by the CFS Research Group of Japan. All clinical departments of internal medicine, pediatrics, psychiatry and neurology at university hospitals and at ordinary hospitals with 200 or more beds were surveyed.

Major results were as follows: (1) Period prevalence adjusted for response rate was 0.85 (0.63 for males and 1.02 for females) per 100,000 population during the year 1992; (2) Based on the first and final dates of hospital visits, the prevalences on January 1 of 1992 and 1993 were 0.40 and 0.60 per 100,000 population, respectively, suggesting an increasing trend; (3) Reported new cases during 1992 were 301, and the response adjusted-incidence was estimated to be 0.46 per 100,000 person-years; (4) The proportion of post-infectious CFS cases was 14.8% for both sexes, and tended to be slightly higher among females than males, but was not related to age. Three clusterings of two cases were reported.

 

Source: Minowa M, Jiamo M. Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan. J Epidemiol. 1996 Jun;6(2):75-80. https://www.jstage.jst.go.jp/article/jea1991/6/2/6_2_75/_pdf (Full article)

 

Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome

Comment on: Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. [J R Soc Med. 1992]

 

As one who has long had a high regard for Dr Shepherd’s reasoned arguments in. the area of chronic fatigue syndrome (CFS) (September. 1992 JRSM, p 588), I am sorry to have to point out a logical inconsistency in his assessment of our work. Postinfectious patients do indeed form a sub-group of those with chronic fatigue syndrome. However, according to the ‘Oxford criteria’, in defining other groups of chronically fatigued patients, a diagnosis of previous infection is not necessary. Thus precipitating infection is not necessary for defining the syndrome itself, as we said in our paper.

Secondly, he might do well to note the way in which our results show energy and mood levels among CFS patients to be at their highest in the midmorning. This does not appear to be the pattern typically found among individuals with a primary diagnosis of depression, as we also point out. We regard this distinction as being potentially important and would hope.that the ME Association might wish to consider its implications. Unfortunately, this point was also missed in a recently unsolicited ‘abstraction’ of our work kindly prepared for us by the International Federation of ME Associations to be published in their Medical Update.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293708/pdf/jrsocmed00106-0076.pdf

 

Source: Wood C. Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. J R Soc Med. 1992 Oct;85(10):650. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293708/