Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients

Abstract:

A 37-kDa binding polypeptide accumulates in peripheral blood mononuclear cell (PBMC) extracts from chronic fatigue syndrome (CFS) patients and is being considered as a potential diagnostic marker (De Meirleir, K., Bisbal, C., Campine, I., De Becker, P., Salehzada, T., Demettre, E., and Lebleu, B. (2000) Am. J. Med. 108, 99-105). We establish here that this low molecular weight 2-5A-binding polypeptide is a truncated form of the native 2-5A-dependent ribonuclease L (RNase L), generated by an increased proteolytic activity in CFS PBMC extracts. RNase L proteolysis in CFS PBMC extracts can be mimicked in a model system in which recombinant RNase L is treated with human leukocyte elastase. RNase L proteolysis leads to the accumulation of two major fragments with molecular masses of 37 and 30 kDa. The 37-kDa fragment includes the 2-5A binding site and the N-terminal end of native RNase L. The 30-kDa fragment includes the catalytic site in the C-terminal part of RNase L. Interestingly, RNase L remains active and 2-5A-dependent when degraded into its 30- and 37-kDa fragments by proteases of CFS PBMC extract or by purified human leukocyte elastase. The 2-5A-dependent nuclease activity of the truncated RNase L could result from the association of these digestion products, as suggested in pull down experiments.

 

Source: Demettre E, Bastide L, D’Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B.Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem. 2002 Sep 20;277(38):35746-51. Epub 2002 Jul 12. http://www.ncbi.nlm.nih.gov/pubmed/12118002

 

Chronic fatigue and chronic fatigue syndrome: a co-twin control study of functional status

Abstract:

Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue may be accompanied by substantial functional disability. A volunteer sample of twins discordant for fatigue was identified from throughout the US. Fatigued twins were classified using three increasingly stringent definitions: (1) > or = 6 months of fatigue (119 pairs); (2) CFS-like illness based on self-report of the Centers for Disease Control and Prevention CFS research definition criteria (74 pairs); and (3) CFS assessed by clinical examination (22 pairs). Twins with chronic fatigue were compared with their unaffected co-twins on the eight standard scales and two physical and mental component summary scales from the medical outcomes study short-form health survey (SF-36). Substantial impairment was observed for fatigued twins across all levels of fatigue, while scores in the healthy twins were similar to US population values. Mean scores among fatigued twins on the physical and mental component summary scales were below 97 and 77%, respectively, of the US population scores. Diminished functional status was found across increasingly stringent classifications of fatigue and was associated with a dramatic decrement in physical functioning. The symptom of fatigue has a pronounced impact on functional status, especially in the domain of physical functioning.

 

Source: Herrell R, Goldberg J, Hartman S, Belcourt M, Schmaling K, Buchwald D. Chronic fatigue and chronic fatigue syndrome: a co-twin control study of functional status. Qual Life Res. 2002 Aug;11(5):463-71. http://www.ncbi.nlm.nih.gov/pubmed/12113393

 

Daily hassles reported by chronic fatigue syndrome and fibromyalgia patients in tertiary care: a controlled quantitative and qualitative study

Abstract:

BACKGROUND: This study aimed at providing insight in the frequency, emotional impact and nature of daily hassles, experienced by patients suffering from chronic fatigue syndrome (CFS) and/or fibromyalgia (FM), compared with patients with a chronic organic disease.

METHODS: One hundred and seventy-seven CFS/FM patients, 26 multiple sclerosis (MS) and 26 rheumatoid arthritis (RA) patients were investigated within 2-6 months after diagnosis. All patients completed a self-report questionnaire assessing daily hassles and associated distress, a visual analogue scale assessing fatigue and pain and a depression and anxiety questionnaire.

RESULTS: CFS/FM patients show a higher frequency of hassles, higher emotional impact and higher fatigue, pain, depression and anxiety levels compared with MS/RA patients. Three hassle themes dominate in the CFS/FM group: dissatisfaction with oneself, insecurity and a lack of social recognition. In contrast, hassles reported by MS/RA patients show a much larger diversity and are not focused on person-dependent problems.

CONCLUSIONS: Patients recently diagnosed as suffering from CFS and/or FM are highly preoccupied and distressed by daily hassles that have a severe impact on their self-image, as well as their personal, social and professional functioning. An optimal therapeutic approach of CFS and FM should take account of this heavy psychosocial burden, which might refer to core themes of these patients’ illness experience.

Copyright 2002 S. Karger AG, Basel

 

Source: Van Houdenhove B, Neerinckx E, Onghena P, Vingerhoets A, Lysens R, Vertommen H. Daily hassles reported by chronic fatigue syndrome and fibromyalgia patients in tertiary care: a controlled quantitative and qualitative study. Psychother Psychosom. 2002 Jul-Aug;71(4):207-13. http://www.ncbi.nlm.nih.gov/pubmed/12097786

 

Evidence for the presence of immune dysfunction in chronic fatigue syndrome

Chronic fatigue syndrome is a medically unexplained ailment characterized by new onset of fatigue accompanied by rheumatological, infectious, and neuropsychiatric symptoms. Because the ailment often begins suddenly with a flu-like presentation, early pathophysiological ideas as to cause included viral infection and immune activation. When early reports identified putative immunological abnormalities in this illness, it was given the name of chronic fatigue and immune dysfunction syndrome, or CFIDS.

The purpose of this review is to evaluate the immunological literature to determine if strong evidence to support this notion exists. We collected and reviewed 239 published papers, of which only 72 fulfilled a set of criteria for use in this review. For this review, we developed the following criteria: papers had to be published in the peer review literature; patients had to be from a group with substantial fatigue lasting at least 6 months (the vast majority fulfilled either the 1988 or the 1994 case definition of chronic fatigue syndrome [CFS]); papers had to compare CFS patients to healthy controls; and actual data had to be shown with evidence of testing for statistical significance. So, for example, when a paper reported no difference between patients and controls for some immunological variables but actual data were not included, we did not include it. Also, if a report compared patient data to normative values rather than to the study’s own control group, we did not include it.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/

 

Source: Natelson BH, Haghighi MH, Ponzio NM. Evidence for the presence of immune dysfunction in chronic fatigue syndrome.  Clin Diagn Lab Immunol. 2002 Jul;9(4):747-52. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/ (Full article)

 

Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome

Abstract:

The elevated RNase L enzyme activity observed in some Chronic Fatigue Syndrome (CFS) patients may be linked to the low exercise tolerance and functional impairment that typify this disease. The purpose of this investigation was to determine if specific indicators of physical performance can predict abnormal RNase L activity in CFS patients. Seventy-three CFS patients performed a graded exercise test to voluntary exhaustion. Forty-six patients had elevated RNase L levels. This measure was employed as the dependent variable in a discriminant function analysis, with peak V02, exercise duration and Karnofsky Performance Scores (KPS) serving as the independent variables. All three variables entered the single significant function (p < 0.001). The elevated RNase L group had a lower peak V02 and duration than the normal group, but a higher KPS. The results suggest that both exercise testing and the RNase L biomarker have potential to aid in the diagnosis of CFS.

 

Source: Snell CR, Vanness JM, Strayer DR, Stevens SR. Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome. In Vivo. 2002 Mar-Apr;16(2):107-9. http://www.ncbi.nlm.nih.gov/pubmed/12073768

 

A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale)

Abstract:

OBJECTIVE: To construct an observer’s rating scale sensitive to change for measuring severity and treatment outcome in fibromyalgia (FM) and chronic fatigue syndrome (CFS) patients.

METHODS: A selection of items from the Comprehensive Psychopathological Rating Scale (CPRS) were repeatedly rated and used as outcome measure of a 24-week treatment study. In the study 100 women, fulfilling the criteria for both FM and CFS, received intermittent injections of a staphylococcus toxoid or placebo. Nine CPRS-items with high baseline incidence (cutoff 70%) were extracted and validated against global ratings and the Fibromyalgia Impact Questionnaire (FIQ). The fibromyalgia and chronic fatigue syndrome rating scale (the FibroFatigue scale) was thereafter formed based upon the extracted items and three supplemented ones. The interrater reliability was tested in 27 consecutive patients of both sexes.

RESULTS: The FibroFatigue scale is an observer’s rating scale with 12 items measuring pain, muscular tension, fatigue, concentration difficulties, failing memory, irritability, sadness, sleep disturbances, and autonomic disturbances (items derived from the CPRS) and irritable bowel, headache, and subjective experience of infection (new items). There was a statistically significant correlation between the CPRS-extracted items and global ratings as well as with the FIQ. The interrater reliability of the new scale was excellent (correlation coefficient.98), irrespective of the patients’ gender.

CONCLUSION: The FibroFatigue scale seems to be a reliable and valid measuring instrument with capacity to monitor symptom severity and change during treatment of FM/CFS patients.

 

Source: Zachrisson O, Regland B, Jahreskog M, Kron M, Gottfries CG. A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale). J Psychosom Res. 2002 Jun;52(6):501-9. http://www.ncbi.nlm.nih.gov/pubmed/12069875

 

The role of fear of physical movement and activity in chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine beliefs in relation to avoidance of activity in chronic fatigue syndrome (CFS) patients.

METHODS: The first phase consisted of modifying an existing chronic pain measure of kinesiophobia-fear of physical movement and activity-and validating it on the CFS population [Tampa Scale of Kinesiophobia-Fatigue (TSK-F); n=129; test-retest: r=.89, P<.001; alpha=.68]. Subscales of Illness Beliefs (alpha=.78) and Beliefs about Activity (alpha=.70) were identified. The second phase consisted of evaluating whether behavioural persistence was predicted by the TSK-F (n=33). Participants were asked to ride an exercise bike for as long as they felt able.

RESULTS: Analyses indicated that behavioural persistence did not correlate with maximal heart rate or resting heart rate, level of tiredness, symptom severity, illness identity or emotional distress. However, the TSK-F did correlate highly with distance travelled and added a significant 15% of the variance in distance after adjustments for gender and physical functioning (PF). The TSK-F Beliefs about Activity subscale appears to be the predictive factor, explaining 12% of the variance in excise performance or rather 12% of the avoidance of exercise.

CONCLUSION: Beliefs about Activity appear to be an important variable in predicting behaviour and avoidance of exercise. As avoidance has been suggested as a key to the maintenance of symptoms, disability and distress in CFS patients, this research has important theoretical, clinical and research implications.

 

Source: Silver A, Haeney M, Vijayadurai P, Wilks D, Pattrick M, Main CJ. The role of fear of physical movement and activity in chronic fatigue syndrome. J Psychosom Res. 2002 Jun;52(6):485-93. http://www.ncbi.nlm.nih.gov/pubmed/12069873

 

Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety, and fatigue

Abstract:

OBJECTIVE: This study was designed to investigate the role of depression, anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers’ objective and subjective cognitive performance.

METHODS: Twenty-three CFS sufferers and 23 healthy control participants were compared on objective and subjective assessments of cognitive performance. Depression, anxiety, and fatigue were also evaluated.

RESULTS: CFS sufferers did not demonstrate any impairment in objective cognitive functioning compared to the control group, and objective performance was not related to their higher levels of depression or their level of fatigue. Depression scores only accounted for a small amount of the variance in CFS sufferers’ lower subjective assessment of their cognitive performance compared to control participants. There were no differences between the groups on anxiety scores.

CONCLUSION: The results are discussed in terms of the heterogeneity of the CFS population and the complex interaction of symptomatological factors that characterise CFS.

 

Source: Short K, McCabe M, Tooley G. Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety, and fatigue. J Psychosom Res. 2002 Jun;52(6):475-83. http://www.ncbi.nlm.nih.gov/pubmed/12069872

 

Illness experience, depression, and anxiety in chronic fatigue syndrome

Abstract:

OBJECTIVE: Given the high rate of psychiatric comorbidity with chronic fatigue syndrome (CFS), we considered two possible correlates of anxiety and depression: lack of illness legitimization and beliefs about limiting physical activity.

METHOD: A total of 105 people diagnosed with CFS reported on their experiences with medical professionals and their beliefs about recovery and completed the depression and anxiety subscales of the Brief Symptom Inventory.

RESULTS: Those who said that their physician did not legitimize their illness (36%) had higher depression and anxiety scores (P’s<.05) than their counterparts. Those who believed that limiting their physical exertion was the path to recovery (55%) had lower depression and anxiety scores (P’s<.01) than their counterparts.

CONCLUSION: Lack of illness legitimization ranked high as a source of dissatisfaction for CFS patients, and it may aggravate psychiatric morbidity. Many CFS patients believed that staying within what they felt to be their physical limits would improve their condition. This belief, and possibly an accompanying sense of control over their symptoms, may alleviate psychiatric morbidity.

 

Source: Lehman AM, Lehman DR, Hemphill KJ, Mandel DR, Cooper LM. Illness experience, depression, and anxiety in chronic fatigue syndrome. J Psychosom Res. 2002 Jun;52(6):461-5. http://www.ncbi.nlm.nih.gov/pubmed/12069870

 

Fatigue after breast cancer and in chronic fatigue syndrome: similarities and differences

Abstract:

OBJECTIVE: Fatigue is investigated in 57 severely fatigued disease-free breast cancer patients and in 57 gender- and age-matched patients with chronic fatigue syndrome (CFS) using multidimensional and multimethod assessment. A comparison between these groups of patients is important to determine whether a cognitive behavioural intervention to reduce fatigue in CFS patients would be appropriate as well for severely fatigued disease-free breast cancer patients.

METHODS: Measurement included computerised questionnaires and a standardised neuropsychological test. Furthermore, patients filled out a daily Self-Observation List (SOL) and wore an actometer during a period of 12 days.

RESULTS: In comparison to severely fatigued disease-free breast cancer patients, CFS patients score more problematic with regard to the level of fatigue, functional impairment, physical activity, pain and self-efficacy. However, a subgroup of severely fatigued disease-free breast cancer patients reports the same amount of problems as CFS patients with regard to psychological well-being, sleep and concentration. Finally, CFS patients and severely fatigued breast cancer patients score equal on measures of social support.

CONCLUSION: There seem to be some similarities but also many differences between severely fatigued breast cancer survivors and females with CFS. Therefore, cognitive behaviour therapy (CBT) to reduce fatigue after treatment for cancer should also differ in certain aspects from cognitive behaviour therapy as it has been developed for patients with CFS.

 

Source: Servaes P, Prins J, Verhagen S, Bleijenberg G. Fatigue after breast cancer and in chronic fatigue syndrome: similarities and differences. J Psychosom Res. 2002 Jun;52(6):453-9. http://www.ncbi.nlm.nih.gov/pubmed/12069869