Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an inflammatory disease of unknown aetiology. Researchers have proposed infectious, neurological and immunological causes of this syndrome. Recently, the xenotropic murine leukemia virus-related virus was detected in 67% of patients with CFS in a US study. This observation is in agreement with one ascertained aspect of the disease: a decreased efficiency in NK cell lytic activity in CFS patients. Here, we analyzed the genomic polymorphism of killer cell immunoglobulin-like receptors (KIRs) and their HLA class I cognate ligands in patients with certified CFS. An excess of KIR3DS1 was found in CFS patients with respect to controls, as well as an increased frequency of the genotype missing KIR2DS5. Forty-four CFS patients and 50 controls also underwent genomic typing for the HLA-ligands. In the patients, a great proportion of KIR3DL1 and KIR3DS1 receptors were found to be missing their HLA-Bw4Ile80 binding motif. We hypothesize that an excess of KIR3DS1, combined with an excess of ligand-free KIR3DL1 and KIR3DS1 receptors, may hamper the clearance of a pathogen via NK cells, thus favouring the chronicity of the infection.

Source: Pasi A, Bozzini S, Carlo-Stella N, Martinetti M, Bombardieri S, De Silvestri A, Salvaneschi L, Cuccia M. Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome. Mol Med Rep. 2011 May-Jun;4(3):535-40. doi: 10.3892/mmr.2011.447. Epub 2011 Mar 4. https://www.ncbi.nlm.nih.gov/pubmed/21468604

Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors

Abstract:

The literature is reviewed and data are presented that relate to a model we have developed to account for the perpetuation of the perplexing disorder currently termed chronic fatigue syndrome (CFS). In patients with CFS there is chronic lymphocyte overactivation with cytokine abnormalities that include perturbations in plasma levels of proinflammatory cytokines and decrease in the ratio of Type 1 to Type 2 cytokines produced by lymphocytes in vitro following mitogen stimulation. The initiation of the syndrome is frequently sudden and often follows an acute viral illness.

Our model for the subsequent chronicity of this disorder holds that the interaction of psychological factors (distress associated with either CFS-related symptoms or other stressful life events) and the immunologic dysfunction contribute to (a) CFS-related physical symptoms (e.g., perception of fatigue and cognitive difficulties, fever, muscle and joint pain) and increases in illness burden and (b) impaired immune surveillance associated with cytotoxic lymphocytes with resulting activation of latent herpes viruses.

 

Source: Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG. Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors. Appl Neuropsychol. 2001;8(1):51-64. http://www.ncbi.nlm.nih.gov/pubmed/11388124

 

Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment

Abstract:

OBJECTIVE: Changes in physical activity are thought to play an important role in maintaining symptoms in chronic fatigue syndrome (CFS). The aim of this study was to describe intraindividual physical activity patterns in more detail and to identify pervasively passive patients.

METHODS: With help of a movement-sensing device, physical activity levels were registered continuously over a 12-day period in 277 CFS patients. Within this registration period, the 10 largest activity peaks were computed. The intensity and duration of these activity peaks and their subsequent rest periods were described and compared to those of 47 healthy controls. In addition, the patients’ 12 daily activity scores were used to identify patients who were characterised by low levels of physical activity throughout the registration period.

RESULTS: The CFS sample had less intense and shorter activity peaks, while the average rest periods that followed these peaks lasted longer. Approximately one-fourth of the CFS sample differed distinctly from the control group and was labelled as pervasively passive.

CONCLUSION: The measurements and classification of actual physical activity levels were found to reduce heterogeneity in the CFS population and therefore could provide the opportunity to optimise behavioural intervention protocols for CFS.

 

Source: van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW, Bleijenberg G. Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. J Psychosom Res. 2000 Nov;49(5):373-9. http://www.ncbi.nlm.nih.gov/pubmed/11164063

 

Sociosomatics and illness in chronic fatigue syndrome

Abstract:

OBJECTIVE: This study examines social processes that construct the course of chronic illness. Specifically, it identifies and describes mechanisms that constitute the process of role constriction in employment for individuals with chronic illness.

METHOD: Sixty-six persons meeting the Centers for Disease Control case definition of chronic fatigue syndrome (CFS) participated in a longitudinal study involving three waves of data collection over 3 years. Qualitative and quantitative methods were combined in the research, which included face-to-face semistructured interviews, telephone interviews, and self-report questionnaires. Materials presented in this study are drawn principally from the Year 1 face-to-face and telephone interviews.

RESULTS: When patterns of symptoms and of the illness course in CFS intersect with work requirements, they impede performance and place ill individuals at risk for job loss. Persons with CFS devise and implement specific strategies to resist role constriction and remain in the work force.

CONCLUSIONS: Role constriction is a social process of marginalization in chronic illness. Opposing forces of marginalization and resistance define the social course in chronic illness and suggest that chronicity can be thought of as a marginalized position in social space.

Comment in: Sociosomatics and illness in CFS. [Psychosom Med. 1999]

 

Source: Ware NC. Sociosomatics and illness in chronic fatigue syndrome. Psychosom Med. 1998 Jul-Aug;60(4):394-401. http://www.ncbi.nlm.nih.gov/pubmed/9710284

 

Government’s expert group has reached consensus on prognosis of chronic fatigue syndrome

EDITOR,-The chronic fatigue syndrome is a complex problem that has attracted a great deal of controversy. Against this background, doctors working for the Department of Social Security and its executive agencies have to give informed and consistent advice. To help in this process I set up an expert group to give me advice on the subject. A consensus view was sought on prognosis and chronicity, which are critical factors in determining a person’s entitlement to a benefit or pension.

The expert group was drawn from a range of medical disciplines with an interest in the condition, so that it reflected a range of opinions; it first met on 6 March this year. A consensus emerged on most of the topics discussed. A report of the meeting has been published and circulated to to those who have a direct interest in the findings.

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359054/pdf/bmj00562-0061b.pdf

 

Source: Aylward M. Government’s expert group has reached consensus on prognosis of chronic fatigue syndrome. BMJ. 1996 Oct 5;313(7061):885. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359054/

 

Chronic fatigue syndrome. Clinical, social psychological problems and management

Abstract:

Fatigue chronic syndrome (SFC) is the heir-at-law of neurasthenia. Both are seen like physical diseases and share certain therapeutic measures, such as sleep; they have the same symbolic function and enable patients as well as doctors reluctant to psychological dimensions of pathology, to get and express sympathy and attention. A strong controversy developed these last years concerning the SFC physiopathology particularly concerning the responsibility of viral infectious agents or psychiatric troubles.

The SFC fatigue is unlikely hysterical or neuromuscular but it probably depends on several associated factors; cerebral neurobiochemistry anomalies (possibly induced by an infection or immune reactions), effort perception trouble, affective trouble, lack of physical activity. The handicap seems to be worse on account of unsuitable care and inefficacious treatment. Especially sleep, which is often beneficial in a short term, is source of ulterior chronicisation. Antidepressants are the only justified pharmacological treatment for SFC at the moment. Referring to the existence and the nature of cognitive distortions, the author suggests a cognitive-behavioural therapy, whose aim is a progressive activity resumption.

 

Source: Wessely S. Chronic fatigue syndrome. Clinical, social psychological problems and management. Encephale. 1994 Nov;20 Spec No 3:581-95. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843055