Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome

Abstract:

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS).

METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster.

RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022).

CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Copyright 2003 Wiley-Liss, Inc.

 

Source: Stewart CC, Cookfair DL, Hovey KM, Wende KE, Bell DS, Warner CL. Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome. Cytometry B Clin Cytom. 2003 May;53(1):26-33. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full  (Full article)

 

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome

Abstract:

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

 

Source: Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN.  Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis. 2003 May 1;36(9):e100-6. Epub 2003 Apr 22. http://cid.oxfordjournals.org/content/36/9/e100.long (Full article)

 

The investigation of chronic fatigue syndrome: a case-study of the limitations of inductive inferences and non-falsifiable hypotheses in medical research

Abstract:

Karl Popper’s argument that deductive logic and falsifiable hypotheses are necessary for the growth of scientific knowledge has been controversial. One approach to assess the relevance of his ideas to medical science has been to evaluate examples of successful research. Another approach is to analyze an unsuccessful investigation. The inconclusive search for a unique ‘chronic fatigue syndrome’ offers a well-documented case-study for this analysis. Over the past 130 years, numerous studies have provided clinical and epidemiological data, which have supported competing hypotheses about the etiology of chronic fatigue. However, few hypotheses have been refuted because it has not been possible to establish objective standards of inquiry for a subjective symptom like fatigue. As a result, intensive research efforts have not converged on correct explanations by eliminating erroneous ideas. This unsuccessful investigation illustrates how non-falsifiable hypotheses are insufficient to advance medical knowledge, even when there is an abundance of empirical data.

 

Source: Hyams KC. The investigation of chronic fatigue syndrome: a case-study of the limitations of inductive inferences and non-falsifiable hypotheses in medical research. Med Hypotheses. 2003 May;60(5):760-6. http://www.ncbi.nlm.nih.gov/pubmed/12710915

 

Chronic fatigue syndrome: new evidence for a central fatigue disorder

Abstract:

Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery.

Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake and ratings of perceived exertion were measured at rest, and during exercise and recovery.

Peak oxygen uptake was significantly lower in the CFS patients compared with controls. Rating of perceived exertion in the patients was higher at all time points measured, including at rest, relative to controls. Levels of free tryptophan (free Trp), the rate-limiting 5-HT precursor, were significantly higher in CFS patients at exhaustion and during recovery, whereas concentrations of branched-chain amino acids (BCAA) and large neutral amino acids (LNAA) were lower in CFS patients at exhaustion, and for LNAA also during recovery. Consequently, the [free Trp]/[BCAA] and [free Trp]/[LNAA] ratios were significantly higher in CFS patients, except at rest.

On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the CFS patients. The significant differences observed in a number of key putative CNS 5-HT and dopaminergic modulators, coupled with the exacerbated perception of effort, provide further evidence for a potentially significant role for CNS mechanisms in the pathogenesis of CFS.

 

Source: Georgiades E, Behan WM, Kilduff LP, Hadjicharalambous M, Mackie EE, Wilson J, Ward SA, Pitsiladis YP. Chronic fatigue syndrome: new evidence for a central fatigue disorder. Clin Sci (Lond). 2003 Aug;105(2):213-8. http://www.ncbi.nlm.nih.gov/pubmed/12708966

 

The head-up tilt test for diagnosing chronic fatigue syndrome

Comment on: The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. [QJM. 2003]

 

Sir,

The recent paper by Naschitz et al.  on the use of the head‐up tilt test with haemodynamic instability score (HIS) in the diagnosis of chronic fatigue syndrome (CFS) provides additional insight about the role of dysautonomia in the pathogenesis of CFS. We would like to raise some points regarding the patient group studied.

The enrolment of clinically‐diagnosed CFS patients and the awareness of diagnosis by technicians prior to performing the tilt test, could result in selection bias. Additionally, generalizing the result of the study, whose population was rich in patients with CFS (40/349, or 11%) to the general population (prevalence of CFS 0.07–0.2%) could be misleading. Using their results of a sensitivity of 90.3% and specificity of 84.5% for a cutoff of HIS >−0.98, a positive head‐up tilt test in a patient presenting with fatigue in the general population would have a positive predictive value of only 0.37–1.15. This result, taken with the fact that around one‐fifth of the patients developed a presyncopal or syncopal episode, would make the test less appealing to patients. However, in a patient presenting with fatigue where clinical diagnosis remained unclear despite lengthy evaluation, the head‐up tilt test could be useful for narrowing down the range of diagnoses.

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/96/5/379.2.long

 

Source: Ghosh AK, Ghosh K. The head-up tilt test for diagnosing chronic fatigue syndrome. QJM. 2003 May;96(5):379-80. http://qjmed.oxfordjournals.org/content/96/5/379.2.long (Full article)

 

The neuroendocrinology of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a common and disabling problem; although most likely of biopsychosocial origin, the nature of the pathophysiological components remains unclear. There has been a wealth of interest in the endocrinology of this condition, which will be reviewed in this article. Most studied has been the hypothalamic-pituitary-adrenal (HPA) axis; although the quality of many studies is poor, the overall balance of evidence points to reduced cortisol output in at least some patients, with some evidence that this is linked to symptom production or persistence.

There is evidence for heightened negative feedback and glucocorticoid receptor function and for impaired ACTH and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication, and ongoing stress, it seems likely that HPA axis disturbance is heterogeneous and of multifactorial etiology in CFS. Studies assessing GH, dehydroepiandrostenedione and its sulfate, melatonin, leptin, and neuroendocrine-monoamine interactions are also reviewed.

There is some evidence from these studies to suggest alterations of dehydroepiandrostenedione sulfate function and abnormal serotonin function in CFS, but whether these changes are of functional importance remains unclear. To obtain a clearer assessment of the etiological and pathophysiological relevance of endocrine changes in CFS, it is suggested that more prospective cohort studies be undertaken in groups at high risk for CFS, that patients with CFS are followed up into recovery, and that multidimensional assessments are undertaken to unravel the influence of the various confounding factors on the observed endocrine changes in CFS.

 

Source: Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr Rev. 2003 Apr;24(2):236-52. http://www.ncbi.nlm.nih.gov/pubmed/12700181

 

Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value

Abstract:

Chronic fatigue syndrome (CFS) is complex illness with unknown aetiology. Recent research shows that patients with CFS have marked alterations in microbial flora, including lowered levels of bifidobacteria and small intestinal bacterial overgrowth (SIBO). Research also indicates that CFS patients are under increased oxidative stress, have a type 2 helper cell dominate cytokine profile, frequently report allergies, have altered essential fatty acid (EFA) status and may have malabsorption of certain micronutrients.

Lactic acid bacteria (LAB) have the potential to influence the immune system in CFS patients by supporting T helper cell 1 driven cellular immunity and may decrease allergies. In addition LAB are strong antioxidants, may improve EFA status, can enhance absorption of micronutrients by protecting the intestinal epithelial barrier, and have been used to treat SIBO. It is our contention that LAB may have a therapeutic role in the treatment of CFS.

 

Source: Logan AC, Venket Rao A, Irani D. Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value. Med Hypotheses. 2003 Jun;60(6):915-23. http://www.ncbi.nlm.nih.gov/pubmed/12699726

 

Chronic fatigue syndrome – medical fact or artifact

Abstract:

Despite extensive investigation, the enigma of Chronic Fatigue Syndrome (CFS) continues to confound medical researchers. It is suggested that this may be due to two impediments inherent in their overall approach to the problem.

Firstly, although fatigue is central to CFS, medical scientists appear not to understand what fatigue itself really is, nor what is its purpose or mode of function. A functional definition of fatigue is suggested to help resolve this.

Secondly, physicians and other researchers – psychologists and alternative medicine practitioners – fail to observe an elementary and fundamental procedure of clinical medicine, namely, that of properly examining their patients before making a diagnosis or providing treatment. The notion of the ‘black hole’ of medicine is introduced. Recognizing the existence of these impediments is considered a self-evident precondition for further significant progress being made in this field.

 

Source: Eidelman D. Chronic fatigue syndrome – medical fact or artifact. Med Hypotheses. 2003 Jun;60(6):840-2. http://www.ncbi.nlm.nih.gov/pubmed/12699708

 

Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells

Abstract:

It has been proposed that cytokines play a role in the pathogenesis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS). However, different studies have reported conflicting results using enzyme-linked immunosorbent assay or polymerase chain reaction to detect cytokines in these conditions.

In the present study, for the first time, the production of inflammatory [interleukin (IL)-1alpha, IL-6, and TNF-alpha] and anti-inflammatory (IL-10) cytokines by CD14+ and CD14- peripheral blood mononuclear cells (PBMC) from chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) patients and sex- and age-matched normal subjects was investigated at the level of individual cells using the technique of intracellular cytokine staining and flow cytometry. Cultures were carried out in the presence of polymyxin B to inhibit the effect of endotoxins on cytokine production by monocytes.

The mean intensity of fluorescence (MIF) and percentage of CD14+ (monocytes) and CD14- (lymphocytes) cytokine-producing mononuclear cells were comparable in patients and controls in either unstimulated or IFN-gamma-stimulated conditions. Our study indicates that dysregulation of cytokine production by circulating monocytes or non-monocytic cells (lymphocytes) is not a dominant factor in the pathogenesis of CFS/FMS.

 

Source: Amel Kashipaz MR, Swinden D, Todd I, Powell RJ. Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells. Clin Exp Immunol. 2003 May;132(2):360-5. http://www.ncbi.nlm.nih.gov/pubmed/12699429

 

Phantom lymphadenopathy. An association with chronic fatigue syndrome

Comment on: Phantom lymphadenopathy. An association with chronic fatigue syndrome. [Postgrad Med J. 2003]

 

Shee reports an association between chronic fatigue syndrome (CFS) and what he regards as a “phantom lymphadenopathy”.1 However, his failure to observe “true lymphadenopathy” in patients with CFS complaining of swollen lymph glands does not exclude a real, albeit subclinical enlargement of those glands, because he did not compare their dimensions with the ones that were measurable before the appearance of patients’ complaints.

As someone who suffered from CFS and reported on its dramatic resolution thanks to old and new drugs for Addison’s disease,2 I clearly remember that my lymph nodes, just a few days after the abrupt onset of CFS, became mildly painful and began to swell gradually. This slow process of enlargement lasted approximately one month. However, even when my lymph glands stopped swelling further (but continued to be mildly painful), their dimensions were still clinically within normal limits. This may indirectly explain why Shee found that “careful examination did not confirm lymphadenopathy” in CFS patients with “self diagnosed enlarged lymph glands”.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742656/pdf/v079p00185a.pdf

 

Source: Baschetti R. Phantom lymphadenopathy. An association with chronic fatigue syndrome. Postgrad Med J. 2003 Mar;79(929):185. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742656/ (Full article)