TGI Friday! Our weekly round-up of recently published research abstracts and announcements | 2 November 2012

From the American Journal of Translational Research, 30 October 2012 (use highlighted link to download of full paper).

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome

Peter D Burbelo(1*), Ahmad Bayat1(*), Jason Wagner(1), Thomas B Nutman(2), James N Baraniuk(3), Michael J Iadarola(1)

(1) Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Cranio- facial Research, National Institutes of Health, Bethesda, MD;
(2) The Laboratory of Parasitic Diseases, National Insti- tute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
(3) Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, D.C. 20007-2197.
(*) Contributed equally to this study.

Abstract

Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases.

Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101). Analysis of the antibody re- sponses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors.

Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity.

To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibod- ies. While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B. However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients.

These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV- 6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.


From the Journal of Clinical Child Psychology and Psychiatry, 23 October 2012. [Epub ahead of print]

Why do young people with CFS/ME feel anxious? A qualitative study.

Fisher H, Crawley E.

Paediatric CFS/ME Service, Royal National Hospital for Rheumatic Diseases, UK.

Abstract

Young people with chronic fatigue syndrome or myalagic encephalopathy (CFS/ME) (CFS/ME) experience higher levels of psychological distress than healthy controls and young people with other chronic illnesses, and it was recently demonstrated that 38% of this population scored above the clinical cut-off on the Spence Child Anxiety Scale. Subscales of social and separation anxiety were consistently high across gender and age groups.

In this study, we used qualitative methods to help us understand more about these two types of anxiety in young people with CFS/ME. Eleven young people (age 12-18) were interviewed. Interviews were self-directed by the participants and were wide ranging. The transcripts were analysed using interpretative phenomenological analysis.

Five superordinate themes were identified: social loss and adjustment; introduction of uncertainty and unpredictability; the vulnerable self; individual differences; and contributions towards recovery. Many themes were identical to those described in young people coping with other chronic illnesses in adolescence.

In addition, young people with CFS/ME describe experiences associated with the perceived illegitimacy of this condition, namely: feeling unable to explain their illness; bullying from peers; disbelief; and distrust from adults around them. This becomes an additional challenge for these young people. Clinicians need to be aware of these problems, and offer appropriate support.


From Lupus, February 2012

Autoimmunity following Hepatitis B vaccine as part of the spectrum of ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’ (ASIA): analysis of 93 cases

Y Zafrir(1*), N Agmon-Levin1(*), Z Paz(1), T Shilton(1), Y Shoenfeld1(2)

(1) The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
(2) Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Yehuda Shoenfeld, MD, FRCP, Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Email: shoenfel@post.tau.ac.il

Abstract

OBJECTIVES

In this study we analyzed the clinical and demographic manifestations among patients diagnosed with immune/autoimmune-mediated diseases post-hepatitis B vaccination. We aimed to find common denominators for all patients, regardless of different diagnosed diseases, as well as the correlation to the criteria of Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants (ASIA).

PATIENTS AND METHODS

We have retrospectively analyzed the medical records of 114 patients, from different centers in the USA, diagnosed with immune-mediated diseases following immunization with hepatitis-B vaccine (HBVv). All patients in this cohort sought legal consultation. Of these, 93/114 patients diagnosed with disease before applying for legal consultation were included in the study. All medical records were evaluated for demographics, medical history, number of vaccine doses, peri-immunization adverse events and clinical manifestations of diseases. In addition, available blood tests, imaging results, treatments and outcomes were recorded. Signs and symptoms of the different immune-mediated diseases were grouped according to the organ or system involved. ASIA criteria were applied to all patients.

RESULTS

The mean age of 93 patients was 26.5 ± 15 years; 69.2% were female and 21% were considered autoimmune susceptible. The mean latency period from the last dose of HBVv and onset of symptoms was 43.2 days. Of note, 47% of patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neuro-psychiatric (70%), fatigue (42%) mucocutaneous (30%), musculoskeletal (59%) and gastrointestinal (50%) complaints. Elevated titers of autoantibodies were documented in 80% of sera tested. In this cohort 80/93 patients (86%), comprising 57/59 (96%) adults and 23/34 (68%) children, fulfilled the required criteria for ASIA.

CONCLUSIONS

Common clinical characteristics were observed among 93 patients diagnosed with immune-mediated conditions post-HBVv, suggesting a common denominator in these diseases. In addition, risk factors such as history of autoimmune diseases and the appearance of adverse event(s) during immunization may serve to predict the risk of post-immunization diseases. The ASIA criteria were found to be very useful among adults with post-vaccination events. The application of the ASIA criteria to pediatric populations requires further study.


From the Journal of Affective Disorders, 10 December 2012.

Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Brenu EW, Ashton KJ, van Driel M, Staines DR, Peterson D, Atkinson GM, Marshall-Gradisnik SM.
Faculty of Health Science and Medicine, Population Health and Neuroimmunology Unit, Bond University, Robina, Queensland, Australia; Faculty of Health Science and Medicine, Bond University, Robina, Queensland, Australia. Electronic address: ekbrenu@bond.edu.au.

Abstract

BACKGROUND

Immune dysfunction associated with a disease often has a molecular basis. A novel group of molecules known as microRNAs (miRNAs) have been associated with suppression of translational processes involved in cellular development and proliferation, protein secretion, apoptosis, immune function and inflammatory processes. MicroRNAs may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), where immune function is impaired. The objective of this study was to determine the association between miRNAs in cytotoxic cells and CFS/ME.

METHODS

Natural Killer (NK) and CD8(+)T cells were preferentially isolated from peripheral blood mononuclear cells from all participants (CFS/ME, n=28; mean age=41.8±9.6years and controls, n=28; mean age=45.3±11.7years), via negative cell enrichment. Following total RNA extraction and subsequent synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of nineteen miRNAs.

RESULTS

There was a significant reduction in the expression levels of miR-21, in both the NK and CD8(+)T cells in the CFS/ME sufferers. Additionally, the expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191 was significantly decreased in NK cells of CFS/ME patients in comparison to the non-fatigued controls.

LIMITATIONS

The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required.

CONCLUSIONS

Collectively these miRNAs have been associated with apoptosis, cell cycle, development and immune function. Changes in miRNAs in cytotoxic cells may reduce the functional capacity of these cells and disrupt effective cytotoxic activity along with other immune functions in CFS/ME patients.


From Archives of Diseases in Childhood, November 2012

British Association of General Paediatrics/British Society for Paediatric Endocrinology & Diabetes

Co-morbid conditions in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) – a retrospective case note review of a large cohort

LM Oliver(1), K Patel(2)

(1) Brighton and Sussex Medical School, Brighton and Sussex University Hospitals (BSUH), Brighton, UK
(2) Royal Alexandra Children’s Hospital, Brighton and Sussex University Hospitals (BSUH), Brighton, UK

Abstract

AIMS

CFS/ME is a complex illness, causing severe incapacitating fatigue, physical and cognitive complaints and is as disabling as many other serious chronic conditions. The prevalence in children is estimated to be 0.2-0.5%. The aim of this study was to take a cohort of children and adolescents with the condition and determine the pattern of co-morbid conditions.

METHODS

Our study took the form of a quantitative and semi-qualitative analysis undertaken as a retrospective case note review of a cohort of 131 patients attending a hospital based, consultant-led specialist CFS/ME clinic. Patients must have been diagnosed with CFS/ME using NICE and RCPCH criteria whilst under the care of a consultant paediatrician to be eligible to be included in the study. Information gathered from their hospital notes included basic demographics, CFS/ME diagnosis information and any co-morbid conditions present.

RESULTS

80% of patients were female which was as expected, with CFS/ME acknowledged to be a female dominated disease. The median age at diagnosis of CFS/ME was 14 years, and there were a total of 38 different symptoms recorded at diagnosis. Other than fatigue, the most common symptoms were headaches, abdominal pain, musculoskeletal pain and decreased concentration and short term memory.

56% of the cohort had at least 1 co-morbid condition. There were 51 separate co-morbid conditions, with the most common conditions being psychiatric, gastrointestinal, respiratory and musculoskeletal problems. 30% of the patients had at least 1 co-morbid condition that the RCPCH lists as a differential diagnosis of CFS/ME.

CONCLUSION

This is the first study exploring co-morbid conditions in children and adolescents with CFS/ME. More than half of the cohort had at least one co-morbid condition. We wish to highlight to paediatricians that the presence of a co-morbid differential diagnosis does not appear to exclude CFS/ME.

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