RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disorder characterized by debilitating fatigue associated with immunological abnormalities. The etiology remains unclear. A low-molecular-mass (37 kDa) isoform of RNase L has been described in peripheral blood mononuclear cell (PBMC) extracts, and the ratio of two isoforms of RNase L (37 kDa/83 kDa) has been proposed as a potential biochemical marker of CFS. In a prospective case-control study, we tested whether the RNase L 37-kDa/83-kDa ratio could discriminate a SFC population.

We compared the ratio of RNase L isoforms in PBMCs from 11 patients with CFS (6 women and 5 men; mean age +/- standard deviation, 43.2 +/- 13.8 years) and PBMCs from 14 healthy well-matched volunteers (10 women and 4 men; age, 39.1 +/- 11.6 years). A ratio of RNase L of 0.4 used as a threshold allowed diagnosis of CFS with high sensitivity (91%; 95% confidence interval [CI], 57 to 99%) and specificity (71%; 95% CI, 41 to 90%). The positive and negative prognostic values were 71% (95% CI, 41 to 90%) and 91% (95% CI, 57 to 99%), respectively.

In the absence of acute infection or chronic inflammation, a high RNase L ratio could distinguish CFS patients from healthy volunteers. Additional large studies and follow-up studies are required to confirm the stability of this high ratio of RNase L isoforms in a CFS group.

Comment in: 37-Kilodalton/83-kilodalton RNase L isoform ratio in peripheral blood mononuclear cells: analytical performance and relevance for chronic fatigue syndrome. [Clin Diagn Lab Immunol. 2005]

 

Source: Tiev KP, Demettre E, Ercolano P, Bastide L, Lebleu B, Cabane J. RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome. Clin Diagn Lab Immunol. 2003 Mar;10(2):315-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150526/ (Full article)

 

Psychiatric adjustment in chronic fatigue syndrome of childhood and in juvenile idiopathic arthritis

Abstract:

BACKGROUND: High rates of psychopathology and of personality problems have been reported in children and adolescents with chronic fatigue syndrome (CFS). It is not clear whether this is consequent on the experience of chronic physical ill health. We compare psychiatric adjustment in children with CFS and in children suffering from another chronic physical disorder (juvenile idiopathic arthritis or JIA).

METHOD: Our sample consisted of 28 children with CFS and 30 with JIA attending tertiary paediatric centres (age range, 11 to 18 years, mean 15, S.D. 2.3). In order to assess psychiatric status and functioning, we used the K-SADS psychiatric interviews, CGAS and Harter Self-Esteem Questionnaire with child subjects; behavioural questionnaires (CBCL) and child personality assessment interviews (PAS) with parent informants.

RESULTS: Psychiatric disorders in the year prior to interview had been present significantly more commonly in the CFS group (72% v. 34% in JIA) and were more impairing to them (CGAS scores of 45 v. 77). Most common diagnoses in both groups were depressive and anxiety disorders. Personality problems were also significantly more frequent in CFS subjects (48% disorder and 26% difficulty v. 11% and 11% in JIA). There were few differences between the two groups in self-esteem.

CONCLUSIONS: Psychopathology and personality problems are common in children and adolescents with severe forms of CFS and cannot be explained strictly through the experience of chronic physical illness.

Comment in: Costs, correlates and consequences of fatigue in children and adults. [Psychol Med. 2003]

 

Source: Rangel L, Garralda ME, Hall A, Woodham S. Psychiatric adjustment in chronic fatigue syndrome of childhood and in juvenile idiopathic arthritis. Psychol Med. 2003 Feb;33(2):289-97. http://www.ncbi.nlm.nih.gov/pubmed/12622307

 

The economic cost of chronic fatigue and chronic fatigue syndrome in UK primary care

Abstract:

BACKGROUND: Chronic fatigue and chronic fatigue syndrome are most often encountered in primary care settings. Given the disabling nature of chronic fatigue it may have a substantial impact on service use and costs as well as on employment. This study estimates this impact.

METHOD: Patients presenting to general practitioners with unexplained chronic fatigue were recruited to the study. Service use over a 3 month period was measured and lost employment recorded. These data were used to estimate economic costs. Patients with chronic fatigue syndrome were compared to patients with only chronic fatigue using a multiple regression model with sample differences controlled.

RESULTS: The mean total cost of services and lost employment across the sample was Pound Sterling1906 for the 3-month period with formal services accounting for 9.3% of this figure. Service use was higher for patients with chronic fatigue syndrome compared to those with chronic fatigue alone. Total 3-month costs were on average higher for chronic fatigue syndrome (Pound Sterling3515 v. Pound Sterling1176) but when sample differences were taken account of the mean difference was reduced to Pound Sterling1406 (P = 0.086). Over 90% of the cost was accounted for by care provided by friends and family members and by lost employment. Patients with dependants had significantly higher costs than those with none and costs were also significantly higher for greater levels of functional impairment.

CONCLUSION: Chronic fatigue imposes substantial economic costs on society, mainly in the form of informal care and lost employment. Treatments need to be developed which recognize these impacts.

Comment in: Costs, correlates and consequences of fatigue in children and adults. [Psychol Med. 2003]

 

Source: McCrone P, Darbishire L, Ridsdale L, Seed P. The economic cost of chronic fatigue and chronic fatigue syndrome in UK primary care. Psychol Med. 2003 Feb;33(2):253-61. http://www.ncbi.nlm.nih.gov/pubmed/12622304

 

Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects

Abstract:

A reduced secretion of cortisol has been proposed as a possible explanation of the symptoms in chronic fatigue syndrome. However, the evidence of hypocortisolism in chronic fatigue syndrome is conflicting.

In order to simultaneously assess possible alterations in adrenocortical sensitivity and secretory adrenal reserve, the authors administered both low-dose and high-dose ACTH to a group of 18 chronic fatigue syndrome patients and 18 age- and gender-matched healthy comparison subjects.

No response differences for salivary and plasma cortisol were detectable after administration of either low-dose or high-dose ACTH, indicating that primary adrenal insufficiency is unlikely to play a significant role in the etiology of chronic fatigue syndrome.

 

Source: Gaab J, Hüster D, Peisen R, Engert V, Heitz V, Schad T, Schürmeyer T, Ehlert U. Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects. Psychosomatics. 2003 Mar-Apr;44(2):113-9. http://www.ncbi.nlm.nih.gov/pubmed/12618533

 

AIDS and CFS/ME: a tale of two syndromes

Abstract:

Both HIV/AIDS and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) presented major challenges for medicine, science and society. This article explores what could have impeded investigation of–and specifically pharmaceutical engagement with–CFS/ME, in contrast to the impressive achievements seen in HIV/AIDS. It explores the obstruction of mind-body dualism in a historical context, and examines some of the possible obstacles to pharmaceutical enquiry. Nothing of real substance is identified that would justify the lack of investment and interest in solutions for patients with CFS/ME.

Comment in: AIDS and CFS/ME. [Clin Med (Lond). 2003]

 

Source: Pinching AJ. AIDS and CFS/ME: a tale of two syndromes. Clin Med (Lond). 2003 Jan-Feb;3(1):78-82. http://www.ncbi.nlm.nih.gov/pubmed/12617422

 

Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue

Abstract:

In some patients complaining of chronic fatigue such as those suffering from the chronic fatigue syndrome (CFS), no underlying physical cause can be clearly identified and they typically present a normal thyroid function. Several studies indicate a dysregulation in the type I interferons (IFN-alpha/beta) pathway in CFS resulting in a sustained upregulation of 2(‘),5(‘)-oligoadenylate synthetases (2-5OAS). Likewise, patients treated with IFN-alpha/beta usually complain of severe fatigue as a limiting side effect.

Beside the 2-5OAS, IFN-alpha/beta induce also the expression of three closely related proteins of unknown function termed the 2-5OAS-like (2-5OASL) proteins. The amino acid sequences of the 2-5OASL proteins display 96% identity with the partial sequence of the thyroid receptor interacting protein (TRIP) 14, further contain two typical thyroid hormone receptor (TR) coregulator domains and feature two ubiquitin C-terminal domains.

From these observations, we raise the hypothesis that the 2-5OASL proteins are TRIPs capable of, respectively, repressing TR transactivation and/or signaling the receptor for destruction by the proteasome. Such molecular mechanisms could explain the development of a clinical hypothyroid state in presence of a normal thyroid function.

 

Source: Englebienne P, Verhas M, Herst CV, De Meirleir K. Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue. Med Hypotheses. 2003 Feb;60(2):175-80. http://www.ncbi.nlm.nih.gov/pubmed/12606231

 

Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome

Abstract:

Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.

 

Source: Chaudhuri A, Condon BR, Gow JW, Brennan D, Hadley DM. Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Neuroreport. 2003 Feb 10;14(2):225-8. http://www.ncbi.nlm.nih.gov/pubmed/12598734

 

Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome

Abstract:

Acute primary Q fever is followed by various chronic sequelae. These include subacute Q fever endocarditis, granulomatous reactions in various organs or a prolonged debilitating post-infection fatigue syndrome (QFS). The causative organism, Coxiella burnetii, persists after an initial infection. The differing chronic outcomes may reflect variations within cytokine and accessory immune control genes which affect regulation of the level of persistence. As a preliminary test of the concept we have genotyped QFS patients and controls for gene variants spanning 15 genes and also examined HLA-B and DR frequencies. QFS patients exhibited a significantly increased frequency of HLA-DR-11 compared with controls and also significant differences in allelic variant frequencies within the NRAMP, and IFN gamma genes. These results indicate a possible genetic role in the expression of overt chronic Q fever. Further studies will be undertaken to increase sample sizes, to survey other forms of chronic Q fever and to examine Q fever patients who have recovered without sequelae.

 

Source: Helbig KJ, Heatley SL, Harris RJ, Mullighan CG, Bardy PG, Marmion BP. Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome. Genes Immun. 2003 Jan;4(1):82-5. http://www.ncbi.nlm.nih.gov/pubmed/12595908

 

Diverse etiologies for chronic fatigue syndrome

Comment on: Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome. [Clin Infect Dis. 2002]

 

SIR—Koelle et al.  recently studied 22 pairs of identical twins discordant for chronic fatigue syndrome and concluded that there was no major contribution for viral infections in the perpetuation of chronic fatigue syndrome (CFS). The authors should be commended for their methodology and the use of well-matched control subjects. However, the study raised several issues.

First, similar to previous studies, the approach of Koelle et al.  was to look for statistical differences among the well-matched pairs with respect to the presence of viral antibodies and, more specifically, the presence of DNA of the viruses studied. Although these viruses were no more prevalent among the patients with CFS than among their healthy twins, one cannot conclude that these viruses are not the cause of CFS in a small subset of patients. CFS has been described in a small number of patients who had had well-documented acute Epstein-Barr virus (EBV), cytomegalovirus (CMV), and parvovirus B19 infections, and many of the patients responded to specific antiviral therapy. Of the first 200 patients with CFS who we evaluated for viral etiologies , only ∼10% had etiologies that were attributed to the viruses studied by Koelle et al. Chlamydia pneumoniae infection, an uncommon, although treatable, cause of CFS, was also dismissed in a previous, smaller study .

You can read the rest of this comment here: http://cid.oxfordjournals.org/content/36/5/671.long

 

Source: Chia JK, Chia A. Diverse etiologies for chronic fatigue syndrome. Clin Infect Dis. 2003 Mar 1;36(5):671-2; author reply 672-3. http://cid.oxfordjournals.org/content/36/5/671.long (Full article)

 

Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome

Abstract:

BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress.

METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD.

RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002).

CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

 

Source: Razumovsky AY, DeBusk K, Calkins H, Snader S, Lucas KE, Vyas P, Hanley DF, Rowe PC. Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome. J Neuroimaging. 2003 Jan;13(1):57-67. http://www.ncbi.nlm.nih.gov/pubmed/12593133