From the Indian Journal of Haematology and Blood Transfusion, March 2014 Epublished 25 October 2012.
Epstein-Barr Virus Infection Masquerading as Acute Leukemia: A Report of Two Cases and Review of Literature.
Chhabra P(1), Law AD(1), Sharma U(2), Suri V(1),Sachdeva MS(3), Kumari S(1), Varma S(1), Malhotra P(1)
1) Department of Internal Medicine, PGIMER, Chandigarh, 160012 India.
2) Department of Pathology, PGIMER, Chandigarh, 160012 India.
3) Department of Hematology, PGIMER, Chandigarh, 160012 India.
Epstein-Barr virus (EBV) is the first herpes virus to be completely sequenced.
It is implicated in diseases from the benign infectious mononucleosis to malignant nasopharyngeal carcinoma, Burkitt’s lymphoma and primary CNS lymphoma in AIDS patients.
It has also been found to be associated with some miscellaneous diseases like chronic fatigue syndrome, multiple sclerosis etc. however causality still remains an issue of debate.
As the virus mainly targets the lymphomonuclear cells and the reticuloendothelial system of the body, it’s various manifestations are often mistaken as leukemic malignancies.
We report two such cases of young adults who had been diagnosed as having acute leukemia on the basis of atypical cells in the peripheral blood.
One patient later turned out to be a classical infectious mononucleosis and second patient had EBV associated hemophagocytic lymphohistiocytosis syndrome.
From International Immunology, 19 January 2014.[Epub ahead of print]
Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis.
Brenu EW(1), Huth TK, Hardcastle SL, Fuller K, Kaur M, Johnston S, Ramos SB, Staines DR, Marshall-Gradisnik SM.
1) School of Medical Science, Griffith University, Gold Coast, QLD 4215, Australia.
Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders.
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels.
The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients.
Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study.
Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols.
The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, gamma deltaT cells and Tregs.
Significant changes were observed in B-cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-alfa – and IFN-gamma in the CFS/ME patients in comparison with the non-fatigued controls.
Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.
From Metabolic Brain Disease, March 2014. Epublished 10 September 2013.
Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways.
Morris G(1), Maes M.
1) Tir Na Nog, Pembrey, Llanelli, UK.
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system.
ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders.
Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage.
This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs.
Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alfa, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown.
The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity.
Lowered levels of antioxidants, zinc and coenzyme Q10, and omega3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways.
Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs.
Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage.
It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypo metabolism and cerebral hypoperfusion.
From Neuroimmunomodulation, epublished 14 February 2014.
Chronic low-grade inflammation in metabolic disorders: relevance for behavioral symptoms.
Lasselin J(1), Capuron L.
1) Nutrition and Integrative Neurobiology (NutriNeuro), UMR 1286, National Institute of Agricultural Research (INRA) and Bordeaux University, Bordeaux, France.
The ability of cytokines to influence cerebral functions and to induce the development of behavioral alterations is well established in conditions of acute or chronic high-grade activation of the innate immune system. Recent evidence suggests that the release of these immune mediators during chronic low-grade endogenous inflammatory processes may also contribute to the development of behavioural alterations.
Metabolic disorders, including obesity, type 2 diabetes and the metabolic syndrome, represent examples of those conditions which are both characterized by a chronic low-grade inflammatory state and an increased prevalence of behavioral disorders. In metabolic disorders, the increased production of acute-phase proteins and cytokines (e.g. C-reactive protein, interleukin-6 and tumour necrosis factor-α), but at relatively low levels, may promote and contribute to the development of behavioral symptoms, including depressive symptoms,
cognitive impairment, fatigue, sleep problems and pain.
This hypothesis is supported by a growing literature referring both to experimental and clinical findings that will be reviewed here.
From Clinical and Cellular Immunology, what date? Open access journal.
Analysis of the Relationship between Immune Dysfunction and Symptom Severity in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Sharni Lee Hardcastle(1*), EkuaWeba Brenu1, Samantha Johnston(1), Thao Nguyen(1), Teilah Huth(1), Manprit Kaur(1), Sandra Ramos(1), Ali Salajegheh(1), Don Staines(1,2( and Sonya Marshall-Gradisnik(1)
1) National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Centre, School of Medical Science, Griffith University, Gold Coast, QLD, Australia
2) Queensland Health, Gold Coast Public Health Unit, Robina, Gold Coast, Queensland, Australia
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a disabling illness, characterized by persistent, debilitating fatigue and a multitude of symptoms. Immunological alterations are prominent in CFS/ME cases, however little is known about the relationship between CFS/ME severity and the extent of immunological dysfunction. The purpose of this study was to assess innate and adaptive immune cell phenotypes and function of two groups of CFS/ME patients, bedridden (severe) and mobile (moderate).
CFS/ME participants were defined using the Centres for Disease Prevention and Control (1994 CDC) Criteria for CFS/ME.
Participants were grouped into healthy controls (n=22, age=40.14 ± 2.38), moderate/mobile (n=23; age=42.52 ± 2.63) and severe/bedridden (n=18; age=39.56 ± 1.51) CFS/ME patients. Flow cytometric protocols were used to examine neutrophil, monocyte, dendritic cells (DCs), iNKT, Treg, B, γδ and CD8+ T cell phenotypes, NK cytotoxic activity and receptors.
The present data found that CFS/ME patients demonstrated significant decreases in NK cytotoxic activity, transitional and regulatory B cells, γδ1T cells, KIR2DL1/DS1, CD94+ and KIR2DL2/L3. Significant increases in CD56-CD16+NKs, CD56dimCD16- and CD56brightCD16-/dim NKs, DCs, iNKT phenotypes, memory and naive B cells were also shown in CFS/ME participants.
Severe CFS/ME patients demonstrated increased CD14-CD16+ DCs, memory and naïve B cells, total iNKT, iNKT cell and NK phenotypes compared to moderate CFS/ME patients.
This study is the first to determine alterations in NK, iNKT, B, DC and γδ T cell phenotypes in both moderate and severe CFS/ME patients. Immunological alterations are present in innate and adaptive immune cells and sometimes, immune deregulation appears worse in CFS/ME patients with more severe symptoms.
It may be appropriate for CFS/ME patient severity subgroups to be distinguished in both clinical and research settings to extricate further immunological pathologies that may not have been previously reported.
From Psychology Research and Behaviour Management, 25 February 2014.
Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome
Elizabeth A Attree(1), Megan A Arroll (1), Christine P Dancey (1), Charlene Griffith (1) Amolak S Bansal(1,2).
1) Chronic Illness Research Team, School of Psychology, University of East London, London, UK;
2) Department of Immunology and the Sutton CFS Service, St Helier Hospital, Carshalton, UK
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS.
In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures.
Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression) to predict cognitive function (self-ratings on prospective and retrospective memory), and cognitive failures.
Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective) memory.
Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition.
We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness may give rise to both fatigue and cognitive deficits independently.