TGI Friday! Our weekly round-up of recently published research abstracts | 25 July 2014

From the Journal of Clinical and Cellular Immunology, 20 June 2014 (open access journal)

Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Ekua W Brenu(1,2*), Donald R Staines(2) and Sonya M Marshall-Gradisnik(1,2)
1) School of Medical Science, Griffith Health Centre, Griffith University, Gold Coast, QLD, Australia
2) The National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Australia

Abstract

OBJECTIVE

Methylation is known to regulate biological processes and alterations in methylation patterns have been associated with a variety of diseases. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an unexplained disorder associated with immunological and molecular changes.

CD4+T cells specifically, regulatory T cells (Tregs) have been implicated in CFS/ME patients where significant increases in Tregs have been observed in these patients. Therefore the objective of this study was to examine methylation in CD4+T cells from CFS/ME patients.

METHODS

The study comprised twenty-five CFS/ME participants and eighteen controls aged between 25-60 years. A volume of 20 ml whole blood was collected from each participant and peripheral blood mononuclear cells were isolated via density gradient centrifugation. A negative isolation kit was used to isolate the CD4+T cells from the peripheral blood samples. Genome wide methylation studies were performed on isolated CD4+T cells using the Illumina Infinium 450 K Human methylation array system. Data analysis was performed using Genome studio and Partek Enrichment software.

RESULTS

120 CpGs were observed to be differentially methylated in the CFS/ME patients in comparison to the controls. Of these 70 were associated with known genes. The majority of the differential methylated regions in the CFS/ME patients were hypomethylated. Additionally, most of the genes with differentially methylated regions in the CFS/ME patients were responsible for apoptosis, cell development, cell function and metabolic activity.

CONCLUSION

The present study demonstrates that epigenetic changes in CD4+T cells may have a potential role in the immunological changes observed in CFS/ME patients.

From the Journal of Clinical and Cellular Immunology, 14 June 2014

Characterization of natural killer cell phenotypes in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Teilah K. Huth(1,2,*), Ekua W. Brenu(1,2), Thao Nguyen(1,2), Sharni L.Hardcastle(1,2), Samantha Johnston(1,2), Sandra Ramos(1,2), Donald R. Staines(2,3) and Sonya M. Marshall-Gradisnik(1,2)

1) National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Griffith University, Southport, QLD, Australia
2) School of Medical Science, Griffith University, Southport, QLD, Australia
3) Queensland Health, Gold Coast Public Health Unit, Robina, QLD, Australia
* Corresponding Author: Teilah Huth BBioMedSc(Hons, National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Griffith University, Parklands, QLD 4222, Australia, Tel: +61 7 5678 9283, E-mail: t.huth@griffith.edu.au

Abstract

OBJECTIVE

Natural Killer (NK) cells are classified into different phenotypes according to the expression of the surface markers CD56 and CD16. Each NK cell phenotype has a role in the immune response through cytotoxic activity or cytokine production. Reduced NK cell cytotoxic activity is a consistent finding in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and investigations into the potential causes of reduced NK cell cytotoxic activity have predominantly focused on total NK cells. The purpose of this study was to investigate and characterize four NK cell phenotypes in CFS/ME.

METHODS

Twenty nine CFS/ME patients (mean age p/m SEM=48.28 p/m 2.63) meeting the 1994 Fukuda definition and 27 healthy controls (mean age p/m SEM=49.15 p/m 2.51) were included in this study. Flow cytometric protocols identified CD56brightCD16-/dim, CD56dimCD16-, CD56dimCD16+ or CD56-CD16+ NK cells for the measurement of surface markers including adhesion molecules CD2, CD18, CD11a, CD11b and CD11c, natural cytotoxicity receptors, Killer Immunoglobulin Like Receptors, signalling lymphocytic activation molecules and cell maturation (CD57). Following stimulation, NK cell phenotype expression of CD107a and CD107b was measured as a marker for degranulation. Intracellular staining measured lytic proteins including perforin, Granzyme A and Granzyme B in the four NK cell phenotypes.

RESULTS

In the CFS/ME group, CD56brightCD16-/dim NK cell co-expression of adhesion molecules CD2 and CD18 was significantly reduced. Granzyme B was significantly decreased in CD56dimCD16+ and CD56-CD16+ NK cells from CFS/ME patients. CD57 expression on CD56dimCD16+ NK cells from CFS/ME patients was significantly increased.

CONCLUSION

This is the first study to characterize four NK cell phenotypes in CFS/ME by investigating surface and intracellular molecules necessary for NK cell effector function. The data suggests that a combination of impairments in CD56dimCD16+ NK cells from CFS/ME patients may contribute to reduced cytotoxic activity of this phenotype.

From Acta Clinica Belgica, 24 July 2014. [Epub ahead of print]

A multidisciplinary network for the care of abnormal fatigue and chronic fatigue syndrome in the provinces of East and West Flanders in Belgium.

E. Tobback(*1); A. Mariman(1); S. Heytens(2); T. Declercq(2); A. Bouwen(3); D. Spooren(1); P. Snoeck(4); K. Van Dessel(5,6); S. D’Hooghe(7); S. Rimbaut(8); D. Vogelaers(1_
*Corresponding author: els.tobback@uzgent.be
1) Department of General Internal Medicine, University Hospital Ghent, Gent, Belgium
2) Department of Family Medicine and Primary Health Care of Ghent University, Ghent University, Gent, Belgium
3) Kliniek voor Onverklaarde Lichamelijke Klachten en Dienst Fysische Geneeskunde, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium
4) AZ Delta, Roeselare, Belgium
5) Gespecialiseerde TrajectBepaling en –Begeleiding (GTB), Gent, Belgium
6) Vlaamse Dienst voor Arbeidsbemiddeling en Beroepsopleiding (VDAB), Brussel, Belgium
7) Axxon, Zaventem, Belgium
8) Department of Rehabilitation and Physiotherapy of Ghent University, University Hospital Ghent, Gent, Belgium

Abstract

The organization of care for patients with the chronic fatigue syndrome (CFS) in tertiary care referral centres from 2002 onwards, was negatively evaluated by the Belgian Health Care Knowledge Centre on the endpoint of socio-professional reintegration. Subsequently, the federal health authorities asked for the elaboration of a new and innovative model of stepped care, aiming at improved integration of diagnosis and treatment into primary care and between levels of health care for patients with CFS.

The reference centre of the University Hospital Ghent took the initiative of recruiting partners in the Belgian provinces of East and West Flanders to guarantee the care for patients with medically unexplained symptoms, in particular abnormal fatigue and CFS.

A new and innovative care model, in which general practitioners play a central role, emphasizes the importance of early recognition of the patient ‘at risk', correct diagnosis and timely referral. Early detection and intervention is essential in order to avoid or minimize illness progression towards chronicity, to safeguard opportunities for significant health improvement as well as to enhance successful socio-professional reintegration.

This approach covers both the large sample of patients developing somatic complaints without obvious disease in an early phase as well as the more limited group of patients with chronic illness, including CFS. Cognitive behavioural therapy and graded exposure/exercise therapy are the evidence-based main components of therapy in the latter. A biopsychosocial model underlies the proposed path of care.

From the online journal argumentcritique.com, 24 July 2014. Click link to download pdf of full text.

False Allegations of Child Abuse in Cases of Childhood Myalgic Encephalomyelitis (ME)

Jane Colby,
Executive Director, The Young ME Sufferers Trust, Ingatestone, Essex.

Abstract

There is no cure for ME (Myalgic Encephalomyelitis). In its absence, management regimes are prescribed, typically based on cognitive behavioural therapy (CBT) and graded exercise therapy (GET). In the case of children this may involve the application of Child Protection powers to enforce treatment.

NICE confirms that patients may withdraw from treatment without effects on future care, but parents who decline, or withdraw children from, management regimes, which may have worsened their illness, can find themselves facing investigation for child abuse or neglect, or have their child forcibly confined to a psychiatric unit.

Tymes Trust has advised 121 families facing suspicion/investigation. To date, none of these families has been found to be at fault. Subsuming ME under the heterogeneous term Chronic Fatigue Syndrome (CFS) has confounded research and treatment and led to disbelief over its severity and chronicity. As evidence points to persistent viral infection, recommendations have been made to separate ME from CFS.

International consensus criteria for ME emphasise post-exertional deterioration as distinct from fatigue. If the child with ME deteriorates under management regimes, re-diagnosis with a psychiatric condition can mask treatment failure and lead to blame attaching to the parent. A more constructive redeployment of resources away from Child Protection investigations into appropriate practical support for these seriously unwell children, should be developed.