Tag: 2008

Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome

Abstract:

Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise.

We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs.

At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (> or = 2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups.

In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 down-regulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

 

Source: Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Mol Med. 2009 Jan-Feb;15(1-2):34-42. doi: 10.2119/molmed.2008.00098. Epub 2008 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/ (Full article)

 

Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. Following two microarray studies, we reported the differential expression of 88 human genes in patients with CFS; 85 of these genes were upregulated and 3 were downregulated.

The top functional categories of these 88 genes were hematologic disease and function, immunologic disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from CFS/ME patients revealed seven subtypes with distinct differences in Short Form (SF)-36 scores, clinical phenotypes, and severity. Gene signatures in each subtype implicate five human genes as possible targets for specific therapy.

Development of a diagnostic test for subtype status is now a priority. The possibility that these subtypes represent individual host responses to particular microbial infections is being investigated and may provide another route to specific therapies for CFS patients.

 

Source: Kerr JR. Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis. Curr Rheumatol Rep. 2008 Dec;10(6):482-91. https://www.ncbi.nlm.nih.gov/pubmed/19007540

 

A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.

Abstract:

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

 

Source: Exley C, Swarbrick L, Gherardi RK, Authier FJ. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses. 2009 Feb;72(2):135-9. doi: 10.1016/j.mehy.2008.09.040. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19004564

 

Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy

Abstract:

OBJECTIVE: To understand more about the problems children with chronic fatigue syndrome (CFS) or myalgic encephalopathy (ME) experience with memory and attention, and to test the feasibility of quantitative measurement of both memory and attention.

DESIGN: Four-item semistructured questionnaire and neuropsychological test battery with 10 psychometric subtests.

SETTING: Family home of the child taking part.

PATIENTS: 20 children with a diagnosis of CFS/ME experiencing memory and/or concentration problems were recruited between April and October 2007 from a regional CFS/ME clinical service (female 13; average age 13.5 years; range 8-16).

METHODS: Each child, parent and teacher was asked to describe the child’s memory and attention problems. Responses were subject to thematic analysis by two independent researchers. In addition, each child completed a battery of 10 tests to measure: processing speed; attention; immediate and delayed memory; working memory; executive function. Raw scores were converted into age-scaled scores and the children’s psychometric scores on the 10 tests taken were compared with normative data using t tests.

RESULTS: Children with CFS/ME, their parents and teachers described problems with focussed attention, sustained attention, recall and stress. Scores for sustained attention (mean 8.1, 95% CI 6.3 to 9.9), switching attention (7.5, 5.5 to 9.4), divided attention (6.9, 5.5 to 8.2), auditory learning (8.2, 6.8 to 9.6) and immediate recall (8.7, 7.3 to 10.0) appeared lower than the normative mean of 10.

CONCLUSIONS: Children with CFS/ME appear to experience problems with attention, which may have adverse implications for verbal memory. These cognitive problems may explain some of the educational difficulties associated with CFS.

 

Source: Haig-Ferguson A, Tucker P, Eaton N, Hunt L, Crawley E. Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy. Arch Dis Child. 2009 Oct;94(10):757-62. doi: 10.1136/adc.2008.143032. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19001478

 

Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy

Abstract:

OBJECTIVE: To investigate factors associated with school attendance and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).

DESIGN: Cross-sectional study.

SETTING: Regional specialist CFS/ME service.

PATIENTS: Children and young people aged under 18 years.

OUTCOME MEASURES: Self-reported school attendance and physical function measured using the physical function subscale of the Short Form 36.

METHODS: Linear and logistic regression analysis of data from self-completed assessment forms on children attending a regional specialist service between 2004 and 2007. Analyses were done in two groups of children: with a completed Spence Children’s Anxiety Scale (SCAS) and with a completed Hospital Anxiety and Depression Scale (HADS).

RESULTS: Of 211 children with CFS/ME, 62% attended 40% of school or less. In children with completed SCAS, those with better physical function were more likely to attend school (adjusted odds ratio (OR) 1.70; 95% CI 1.36 to 2.13). This was also true for those with completed HADS (adjusted OR 2.05; 95% CI 1.4 to 3.01). Increasing fatigue and pain and low mood were associated with worse physical function. There was no evidence that anxiety, gender, age at assessment, family history of CFS/ME or time from onset of symptoms to assessment in clinic were associated with school attendance or physical function.

IMPLICATIONS: Paediatricians should recognise that reduced school attendance is associated with reduced physical function rather than anxiety. Improving school attendance in children with CFS/ME should focus on evidence-based interventions to improve physical function, particularly concentrating on interventions that are likely to reduce pain and fatigue.

 

Source: Crawley E, Sterne JA. Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy. Arch Dis Child. 2009 Oct;94(10):752-6. doi: 10.1136/adc.2008.143537. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19001477

 

Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome

Abstract:

BACKGROUND: Systems biologic approaches such as Weighted Gene Co-expression Network Analysis (WGCNA) can effectively integrate gene expression and trait data to identify pathways and candidate biomarkers. Here we show that the additional inclusion of genetic marker data allows one to characterize network relationships as causal or reactive in a chronic fatigue syndrome (CFS) data set.

RESULTS: We combine WGCNA with genetic marker data to identify a disease-related pathway and its causal drivers, an analysis which we refer to as “Integrated WGCNA” or IWGCNA. Specifically, we present the following IWGCNA approach: 1) construct a co-expression network, 2) identify trait-related modules within the network, 3) use a trait-related genetic marker to prioritize genes within the module, 4) apply an integrated gene screening strategy to identify candidate genes and 5) carry out causality testing to verify and/or prioritize results. By applying this strategy to a CFS data set consisting of microarray, SNP and clinical trait data, we identify a module of 299 highly correlated genes that is associated with CFS severity. Our integrated gene screening strategy results in 20 candidate genes. We show that our approach yields biologically interesting genes that function in the same pathway and are causal drivers for their parent module. We use a separate data set to replicate findings and use Ingenuity Pathways Analysis software to functionally annotate the candidate gene pathways.

CONCLUSION: We show how WGCNA can be combined with genetic marker data to identify disease-related pathways and the causal drivers within them. The systems genetics approach described here can easily be used to generate testable genetic hypotheses in other complex disease studies.

 

Source: Presson AP, Sobel EM, Papp JC, Suarez CJ, Whistler T, Rajeevan MS, Vernon SD, Horvath S. Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome.BMC Syst Biol. 2008 Nov 6;2:95. doi: 10.1186/1752-0509-2-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625353/ (Full article)

 

Vaccination as teenagers against meningococcal disease and the risk of the chronic fatigue syndrome

Abstract:

The etiology of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is unknown. In Norway, a vaccine against Neisseria meningitides group B was administered to teenagers in 1988–1989 in a protection trial. In order to estimate the relative risk of CFS/ME according to vaccine history, we conducted a case-control study in 2007, with 201 cases diagnosed at one of two hospitals and 389 controls. The adjusted odds ratio for CFS/ME was 1.06 (95% CI: 0.67-1.66) for subjects who received the active vaccine contrasted to subjects who did not. Using this design, no statistically significant association between vaccination against meningococcal disease in teenagers and occurrence of CFS/ME could be observed.

 

Source: Magnus P, Brubakk O, Nyland H, Wold BH, Gjessing HK, Brandt I, Eidem T, Nøkleby H, Stene-Larsen G. Vaccination as teenagers against meningococcal disease and the risk of the chronic fatigue syndrome. Vaccine. 2009 Jan 1;27(1):23-7. doi: 10.1016/j.vaccine.2008.10.043. Epub 2008 Nov 5. https://www.ncbi.nlm.nih.gov/pubmed/18984023

 

Symptoms, impairment and illness intrusiveness–their relationship with depression in women with CFS/ME

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an illness in which physiological and psychological factors are believed to interact to cause and maintain CFS/ME in an individual predisposed to it. The various symptoms and impairments associated with CFS/ME have a large impact on quality of life. The purpose of the present study was to identify the extent to which the core symptoms and impairments associated with CFS/ME relate to depression in women with CFS/ME, and to discover whether these relationships were mediated by illness intrusiveness. CFS/ME was found to be a highly intrusive illness, intruding into more life domains and to a greater degree than other illnesses. The effects of both symptoms and impairment on depression were, in part, mediated by illness intrusiveness. Although symptoms severity and impairment had both direct and indirect effects on depression, illness intrusiveness was the strongest predictor of depression.

 

Source: Dancey CP, Friend J. Symptoms, impairment and illness intrusiveness–their relationship with depression in women with CFS/ME. Psychol Health. 2008;23(8):983-99. doi: 10.1080/08870440701619957. https://www.ncbi.nlm.nih.gov/pubmed/25160923

 

Traditional chinese medicine for chronic fatigue syndrome

Abstract:

More and more patients have been diagnosed as having chronic fatigue syndrome (CFS) in recent years. Western drug use for this syndrome is often associated with many side-effects and little clinical benefit.

As an alternative medicine, traditional Chinese medicine (TCM) has provided some evidences based upon ancient texts and recent studies, not only to offer clinical benefit but also offer insights into their mechanisms of action. It has perceived advantages such as being natural, effective and safe to ameliorate symptoms of CFS such as fatigue, disordered sleep, cognitive handicaps and other complex complaints, although there are some limitations regarding the diagnostic standards and methodology in related clinical or experimental studies.

Modern mechanisms of TCM on CFS mainly focus on adjusting immune dysfunction, regulating abnormal activity in the hypothalamic-pituitary-adrenal (HPA) axis and serving as an antioxidant. It is vitally important for the further development to establish standards for ‘zheng’ of CFS, i.e. the different types of CFS pathogenesis in TCM, to perform randomized and controlled trials of TCM on CFS and to make full use of the latest biological, biochemical, molecular and immunological approaches in the experimental design.

 

Source: Chen R, Moriya J, Yamakawa J, Takahashi T, Kanda T. Traditional chinese medicine for chronic fatigue syndrome. Evid Based Complement Alternat Med. 2010 Mar;7(1):3-10. doi: 10.1093/ecam/nen017. Epub 2008 Feb 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816380/ (Full article)

 

Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome

Abstract:

BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. One theory about the aetiology of this hypocortisolism is that it occurs late in the course of CFS via factors such as inactivity, sleep disturbance, chronic stress and deconditioning. We aimed to determine whether therapy aimed at reversing these factors–cognitive behavioural therapy for CFS–could increase cortisol output in CFS.

METHODS: We measured diurnal salivary cortisol output between 0800 and 2000 h before and after 15 sessions (or 6 months) of CBT in 41 patients with CDC-defined CFS attending a specialist, tertiary outpatient clinic.

RESULTS: There was a significant clinical response to CBT, and a significant rise in salivary cortisol output after CBT.

LIMITATIONS: We were unable to control for the passage of time using a non-treated CFS group.

CONCLUSIONS: Hypocortisolism in CFS is potentially reversible by CBT. Given previous suggestions that lowered cortisol may be a maintaining factor in CFS, CBT offers a potential way to address this.

 

Source: Roberts AD, Papadopoulos AS, Wessely S, Chalder T, Cleare AJ. Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome. J Affect Disord. 2009 May;115(1-2):280-6. doi: 10.1016/j.jad.2008.09.013. Epub 2008 Oct 19. https://www.ncbi.nlm.nih.gov/pubmed/18937978