TGI Friday! | Our regular round-up of recently published research abstracts | 12 April 2013

From the International Journal of Clinical Medicine, March 2013.

Enhanced Gene Expression Following Vaccination in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Ekua W. Brenu1(2*), Gunn M. Atkinson(2). Mieke L. van Driel(3), Sanne Kreijkamp-Kaspers(4), Don R. Staines(2,5), Sonya M. Marshall-Gradisnik(1,2)
1 School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Australia;
2 National Center for Neuroimmu- nology and Emerging Diseases, Griffith University, Gold Coast, Australia;
3 Discipline of General Practice, School of Medicine, The University of Queensland, Brisbane, Australia;
4 Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia; Health
5 Queensland Health, Gold Coast Public Health Unit, Gold Coast, Australia.
Email: e.brenu@griffith.edu.au

Abstract

Vaccines have been shown to cause differential expression of genes and increase antibody titers against antigens. 

Influenza vaccines may have an effect on unexplained disorders such as Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Immunological changes have been identified following immunization with trivalent influenza vaccine (TIV).

The objective of this pilot study was to examine the consequences of TIV on cytokine and cytotoxic genes in CFS/ME.

Peripheral blood mononuclear cells were preferentially isolated from whole blood of 7 CFS/ME  patients and 8 controls. Following total RNA extraction and synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of mRNAs for cytotoxic genes (perforin (PRF1), granzyme A (GZMA), granzyme B (GZMB) and cytokine genes.

GZMB was significantly increased overall in the CFS/ME patients compared to the controls. GZMA was significantly increased 28 days after vaccination while PRF1 was reduced prevaccination but increased 14 days post-vaccination in the CFS/ME patients. There were no significant changes in cytokine genes pre or post vaccination.

Administration of TIV may increase the expression of lytic genes in CFS/ME and this may contribute to the increase in cytotoxic activity we observed in these
patients post vaccination.

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From Australian Family Physiciann, April 2013.

Chronic fatigue syndrome – A patient-centered approach to management

Megan Arroll(1), Bruce Arroll(2)
1 Director of Research, The Optimum Health Clinic, Research Department, London, England
2 Professor in General Practice and Primary Health Care, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
* Correspondence afp@racgp.org.au

Abstract

BACKGROUND

Chronic fatigue syndrome (myalgic encephalomyelitis) is a diagnosis that can attract feelings of stigma in the patient due to the lack of a definite diagnostic biomarker. To ensure that the patient firstly understands the diagnosis, and subsequently is comfortable with the treatment suggested, a patient centred approach is advised within the consultation.

OBJECTIVE

This article presents a hypothetical case and uses this to give guidance on methods for negotiating the diagnosis and treatment of chronic fatigue syndrome.

DISCUSSION

It is important to reassure the patient that negative investigation results and the suggestion of treatment options that are also used for depressive illness (eg. antidepressants and cognitive behavioural therapy), does not mean that their illness experience is fabricated or that they are being treated for depression. Once red flag features are ruled out and any exclusory illnesses identified, a multidisciplinary pragmatic rehabilitation program can be implemented. This includes strategies for increasing social support, liaising with employers and graded return to activities in a ‘What matters to you?' approach.

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From Journal of Translational Medicine, 9 April 2013.

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

Elizabeth Ann Stringer(1), Katharine Susanne Baker(1), Ian R Carroll(1), Jose G Montoya(2), Lily Chu(5). Holden T Maecker(3), Jarred W Younger(1,4,*)
1 Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA 94304, USA
2 Department of Medicine, Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94304, USA
3 Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA
4 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304-1336, USA 5 Independent Consultant, Stanford, CA 94304, USA
* Corresponding author. 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304- 1336, USA

Abstract (provisional)

BACKGROUND

Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.

METHODS

Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology.

Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity.

A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected.

Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women.

As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.

RESULTS

Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. In a secondary analysis, we widened the analyses to 50 other cytokines. In participants with CFS the relationship between immune factors and fatigue was so strong that we were able to distinguish low fatigue days from high fatigue days with 78.3% accuracy, using only cytokines as predictors. Additionally, when this CFS-trained model was applied to the control dataset, the model performed at a chance level. The results support a role of inflammation in CFS pathology.

The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.

CONCLUSIONS

Our results support the role of cytokines in the pathophysiology of CFS.

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From American Journal of Translational Research, 28 March 2013.

Prefrontal lactate predicts exercise-induced cognitive dysfunction in Gulf War Illness.

Rayhan RU, Raksit MP, Timbol CR, Adewuyi O, Vanmeter JW, Baraniuk JN.
Division of Rheumatology, Immunology and Allergy; Department of Medicine, Georgetown University Medical Center Room 3004F 3rd Floor PHC Building, 3800 Reservoir Road, NW, Washington, DC 20007, USA

Abstract

BACKGROUND

25% to 30% of Veterans deployed to the 1990 to 1991 Persian Gulf War exhibit an idiopathic syndrome of chronic fatigue, exertional exhaustion, pain, hyperalgesia, cognitive and affective dysfunction known as Gulf War Illness (GWI).

METHODS

Gulf War veterans (n=15) and sedentary veteran and civilian controls (n=11) completed a 2-back working memory test in an fMRI before and after two bicycle exercise stress test. We performed single voxel (1)H MRS to evaluate brain metabolic differences in the left anterior cingulate cortex and the changes associated with exercise.

RESULTS

Eight GWI subjects increased their 2-back scores after exercise (labelled increasers) and seven GWI subjects decreased their 2-back scores after exercise (labelled decreasers). These phenotypic responses were absent for controls. Decreasers had significantly elevated prefrontal lactate levels compared to Increasers prior to completion of the exercise stress tests. Evaluation of prefrontal lactate levels prior to exercise demonstrated predictability (ROC analysis) of the two diametrically opposed subgroups.

CONCLUSION

Prefrontal lactate levels may be a potential biomarker for exercise-induced subgroups in GWI. The alterations in brain energetics may be in part responsible for a subgroup of GWI and underlie some of the symptoms present in the patient population.

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Toxins, 11 April 2013,

Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome

Joseph H. Brewer(1,*), Jack D. Thrasher(2), David C. Straus(3), Roberta A. Madison(4) and Dennis Hooper(5).
1 Plaza Infectious Disease and St. Luke's Hospital, 4320 Wornall Road, Suite 440, Kansas City, MO 64111, USA
2 Citrus Heights, CA 95610, USA
3 Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
4 California State University, Northridge, CA 91330, USA
5 RealTime Laboratories, Carrollton, TX 75010, USA
* Author to whom correspondence should be addressed.

This article appeared in the Special Issue Mycotoxins and Human Diseases

Abstract

Over the past 20 years, exposure to mycotoxin producing mold has been recognized as a significant health risk.

Scientific literature has demonstrated mycotoxins as possible causes of human disease in water-damaged buildings (WDB).

This study was conducted to determine if selected mycotoxins could be identified in human urine from patients suffering from chronic fatigue syndrome (CFS).

Patients (n = 112) with a prior diagnosis of CFS were evaluated for mold exposure and the presence of mycotoxins in their urine.

Urine was tested for aflatoxins (AT), ochratoxin A (OTA) and macrocyclic trichothecenes (MT) using Enzyme Linked Immunosorbent Assays (ELISA).

Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin (one in the equivocal range). Almost 30% of the cases had more than one mycotoxin present. OTA was the most prevalent mycotoxin detected (83%) with MT as the next most common (44%).

Exposure histories indicated current and/or past exposure to WDB in over 90% of cases.

Environmental testing was performed in the WDB from a subset of these patients.

This testing revealed the presence of potentially mycotoxin producing mold species and mycotoxins in the environment of the WDB.

Prior testing in a healthy control population with no history of exposure to a WDB or moldy environment (n = 55) by the same laboratory, utilizing the same methods, revealed no positive cases at the limits of detection.

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