2011 – Page 16 – American ME and CFS Society

Heterologous immunity: immunopathology, autoimmunity and protection during viral infections

There is a strong association between infection-related cell-mediated immunity and autoimmune diseases such as diabetes, multiple sclerosis (MS), rheumatoid arthritis (RA) and lupus erythematosis (SLE)1. Infections have also been associated with unusual immunopathologies of unknown origin, such as Wegner granulomatosis, sarcoidosis, colitis, panniculitis, bronchiolitis obliterans and even chronic fatigue syndrome. Despite exhaustive efforts, a definitive link between one particular pathogen and any of one these pathologies has never been found. More often several pathogens have become associated with each of these conditions. For instance multiple sclerosis has been associated with Epstein Barr virus (EBV), measles virus, HHV-6, varicella-zoster virus, and Picornaviruses2-6. Panniculitis in the form of erythema nodosum and bronchiolitis obliterans have both been associated with unusual cell-mediated immune responses that occur following non-specified viral or intracellular bacterial infections 7-9. Erythema nodosum, which has also been associated with Crohn’s disease8, is a very painful condition, where nodules of inflamed subcutaneous fat often on the shins and forearms persist for months. There is no known therapy. Bronchiolitis obliterans is a lethal condition in humans where the bronchioles become occluded with immune cells and fibrinous material, with no known cause or treatment9.

Chronic fatigue syndrome (CFS) is another unusual multisystem disease which is thought to be associated with immune dysregulation. Over the past two decades millions of patients world wide have suffered from a clinical syndrome of disabling fatigue, myalgias, palpitations and cognitive dysfunction that lasts longer than 6 months. In 50% of cases it develops after a mild viral illness. Cases may appear sporadically or in clusters10,11. Many attempts have been made to define the syndrome on the basis of an etiologic agent. These agents have included Epstein-Barr virus10, Brucella12, Candida albicans13, Borrelia burgdorferi, and human herpesvirus-614,15. More recently it has been associated with enteroviruses and xenoretroviruses 16-18. The general conclusion has been that it is unlikely that the syndrome is caused by a single etiologic agent. The mechanisms mediating CFS are poorly understood, and there are few well designed studies examining its cause. The symptoms of CFS are similar to those experienced during viral infections such as infectious mononucleosis or influenza or in the setting of therapy with cytokines such as interferon or interleukin-2. It has been speculated that some or all the symptoms are reflective of an altered immune response to some pathogen with over production of one or more cytokines. An alternative hypothesis suggests that a number of infectious agents are involved and result in a regulatory imbalance of cytokines and the patient with CFS is unable to reestablish the appropriate balance of cytokines. These theories have been supported by reports of immune deficiency seen associated with CFS19.

Source: Selin LK, Wlodarczyk MF, Kraft AR, Nie S, Kenney LL, Puzone R, Celada F. Heterologous immunity: immunopathology, autoimmunity and protection during viral infections. Autoimmunity. 2011 Jun;44(4):328-47. doi: 10.3109/08916934.2011.523277. Epub 2011 Jan 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633594/ (Full article)

Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up

Abstract:

Chronic fatigue syndrome (CFS) produces physical and neurocognitive disability that significantly affects health-related quality of life (HRQL). Multidisciplinary treatment combining graded exercise therapy (GET) cognitive behavioural therapy (CBT) and pharmacological treatment has shown only short-term improvements.

Aim: To compare the effects on HRQL of (1) multidisciplinary treatment combining CBT, GET, and pharmacological treatment, and (2) usual treatment (exercise counselling and pharmacological treatment) at 12 months of follow-up.

Design: Prospective, randomized controlled trial with a follow-up of 12 months after the end of treatment.

Method: Patients consecutively diagnosed with CFS (Fukuda criteria) were randomly assigned to intervention (n = 60) or usual treatment (n = 60) groups. HRQL was assessed at baseline and 12 months by the Medical Outcomes Study Short-Form questionnaire (SF-36). Secondary outcomes included functional capacity for activities of daily living measured by the Stanford Health Assessment Questionnaire (HAQ) and comorbidities.

Results: At baseline, the two groups were similar, except for lower SF-36 emotional role scores in the intervention group. At 12 months, the intervention did not improve HRQL scores, with worse SF-36 physical function and bodily pain scores in the intervention group.

Conclusion: Multidisciplinary treatment was not superior to usual treatment at 12 months in terms of HRQL. The possible benefits of GET as part of multidisciplinary treatment for CFS should be assessed on an individual patient basis.

Source: Núñez M, Fernández-Solà J, Nuñez E, Fernández-Huerta JM, Godás-Sieso T, Gomez-Gil E. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clin Rheumatol. 2011 Mar;30(3):381-9. doi: 10.1007/s10067-010-1677-y. Epub 2011 Jan 15. https://www.ncbi.nlm.nih.gov/pubmed/21234629

For a list of references see: http://link.springer.com/article/10.1007/s10067-010-1677-y

CFS prevalence and risk factors over time

Abstract:

The present natural history study examined the course of CFS from 1995-97 (Wave 1) to approximately 10 years later (Wave 2) from a random, community-based, multi-ethnic population. The rate of CFS remained approximately the same over the period of time from Wave 1 to Wave 2, although a high level of mortality was found (18% of those with medical or psychiatric exclusions group, 12.5% for the CFS group). Physical measures of disability and fatigue, along with measures of specific somatic symptoms, better differentiate individuals who later are diagnosed with CFS than more psychosocial measures such as stress and coping.

Source: Jason LA, Porter N, Hunnell J, Rademaker A, Richman JA. CFS prevalence and risk factors over time. J Health Psychol. 2011 Apr;16(3):445-56. doi: 10.1177/1359105310383603. Epub 2011 Jan 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166209/ (Full article)

Diagnostic accuracy of symptoms characterising chronic fatigue syndrome

Abstract:

PURPOSE: To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS).

METHODS: A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n = 16 individuals with CFS; n = 14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24 h apart.

RESULTS: Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve = 0.864, 95% confidence interval [CI]: 0.706-1.00, p = 0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p < 0.001). A significant binary logistic regression model (p < 0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects.

CONCLUSIONS: A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.

Source: Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-75. doi: 10.3109/09638288.2010.546936. Epub 2011 Jan 6. https://www.ncbi.nlm.nih.gov/pubmed/21208154

Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity

Abstract:

OBJECTIVE: The underlying aetiology of chronic fatigue syndrome is currently unknown; however, in the light of carnitine’s critical role in mitochondrial energy production, it has been suggested that chronic fatigue syndrome may be associated with altered carnitine homeostasis. This study was conducted to comparatively examine full endogenous carnitine profiles in patients with chronic fatigue syndrome and healthy controls.

DESIGN: A cross-sectional, observational study.

SETTING AND SUBJECTS: Forty-four patients with chronic fatigue syndrome and 49 age- and gender-matched healthy controls were recruited from the community and studied at the School of Pharmacy & Medical Sciences, University of South Australia.

MAIN OUTCOME MEASURES: All participants completed a fatigue severity scale questionnaire and had a single fasting blood sample collected which was analysed for l-carnitine and 35 individual acylcarnitine concentrations in plasma by LC-MS/MS.

RESULTS: Patients with chronic fatigue syndrome exhibited significantly altered concentrations of C8:1, C12DC, C14, C16:1, C18, C18:1, C18:2 and C18:1-OH acylcarnitines; of particular note, oleyl-L-carnitine (C18:1) and linoleyl-L-carnitine (C18:2) were, on average, 30-40% lower in patients than controls (P < 0.0001). Significant correlations between acylcarnitine concentrations and clinical symptomology were also demonstrated.

CONCLUSIONS: It is proposed that this disturbance in carnitine homeostasis is reflective of a reduction in carnitine palmitoyltransferase-I (CPT-I) activity, possibly a result of the accumulation of omega-6 fatty acids previously observed in this patient population. It is hypothesized that the administration of omega-3 fatty acids in combination with l-carnitine would increase CPT-I activity and improve chronic fatigue syndrome symptomology.

Source: Reuter SE, Evans AM. Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity. J Intern Med. 2011 Jul;270(1):76-84. doi: 10.1111/j.1365-2796.2010.02341.x. Epub 2011 Jan 19. https://www.ncbi.nlm.nih.gov/pubmed/21205027

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.

RESULTS: No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffected twins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetected hepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation.

CONCLUSIONS: Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.

Source: Sullivan PF, Allander T, Lysholm F, Goh S, Persson B, Jacks A, Evengård B, Pedersen NL, Andersson B. An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue. BMC Microbiol. 2011 Jan 2;11:2. doi: 10.1186/1471-2180-11-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022642/ (Full article)

Adolescents with severe chronic fatigue syndrome can make a full recovery

Abstract:

The needs of children and adolescents severely affected by chronic fatigue syndrome, myalgic encephalomyelitis (CFS/ME) are currently inadequately addressed in the UK. Sadly, there are few specialists addressing the needs of these patients who are primarily bed-bound, wheelchair users or who can only leave home on an infrequent basis. Uncertainty about what to offer as well of a lack of funding may play a part. Action for Young people with ME (AYME) suggests that at least 350 severely affected children/adolescents are receiving little or inadequate care to help them overcome this debilitating illness. This case report illustrates how recovery can occur with pragmatic rehabilitation combined with a committed compassionate family based approach.

Source: Burgess M, Chalder T. Adolescents with severe chronic fatigue syndrome can make a full recovery. BMJ Case Rep. 2011 May 10;2011. pii: bcr0120113716. doi: 10.1136/bcr.01.2011.3716. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091076/ (Full article)