Tracking post-infectious fatigue in clinic using routine Lab tests

Abstract

Background: While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. Methods: Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis. Classification models separating PI-CFS from controls were constructed at each time point using stepwise subset selection. Results: Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups.

Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?

“…For example, research teams have reported impaired phagocytosis and evidence of immune senescence in monocytes characterised by reduced expression of HLA-DR antigens (Gupta and Vayuvegula 1991 ; Prieto-Domínguez et al 2016 ; Straus et al 1993 ) while a recent study revealed a decrease in DCs overall but an increase in myeloid DCs, which is a characteristic of DC populations in a state of endotoxin tolerance as previously discussed (Brenu et al 2014b ). Several abnormalities in neutrophil phenotype and function have also been reported with reduced respiratory burst and phagocytic capacity together with an increased tendency to apoptosis being the most commonly reported findings (Brenu et al 2010 ; Bryceson et al 2006 ; Harvey et al 2016 ; Kennedy et al 2004 ). Other evidence of immune downregulation in at least some patients with CFS/ME includes downregulated TLR4 activity (Light et al 2009 , 2013 ; White et al 2012 ) and a pattern of miRNA expression consistent with immune suppression induced by TGF-β1 signalling (Brenu et al 2014a ; Petty et al 2016 ).…”

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

“…It is indicative of a wider metabolic derangement than a block of PDH ( 275 ) would be expected to lead to. There are several papers on hormones ( 322 ), including glucocorticoids ( 257 ) and transient receptor potential channel hormones ( 222 ), and their receptors ( 106 , 107 , 109 ), in ME/CFS. It is conceivable that parts of the autonomic dysfunction can be explained in this way.…”

Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort

“…One possible explanation for our findings is that there is a heritable difference in a physiological mechanism, which increases susceptibility to CFS/ME [27] and which also affects sleep patterns in such a way that children tend to have later bedtimes. Putative common causes for abnormal sleep and increased CFS/ME susceptibility revolve around the hypothalamic–pituitary–adrenal (HPA) axis function [28] , [29] , manifesting as differences in cortisol [30] , [31] , adrenocorticotropic hormone [32] and melatonin [33] , and around the autonomic nervous system function, manifesting as differences in heart rate variability [34] , [35] , [36] , [37] .…”