MEDICAL UPDATE May 2000

De Meirleir, K et al.  37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome.  American Journal of Medicine, 2000, 108, 2, 99-105.

Past studies on the blood of patients with CFS have revealed abnormalities in the antiviral, ribonuclease L pathway. (Click on button for a more detailed explanation of this pathway).

The most recent study has just been published by Prof. De Meirleir and his colleagues from Belgium. They tested 57 patients with acute or subacute post-viral onset CFS (CDC criteria '88 and '94) and 53 control subjects (28 healthy subjects and 25 patients with depression or fibromyalgia).

A unique 37 kDa form of RNase L was found in 88% of the patients with CFS and 28% of the controls (p<0.01). When present, the amount of the 37 kDa form was very low in the control groups. The ratio of 37 kDa to the normal 80 kDa form of RNase L was high in 72% of CFS patients compared with 11% of the controls and none of the people with fibromyalgia or depression.  In other words, by calculating the ratio of the low molecular weight RNase L to the normal 80 kDa RNase L, people with CFS can be distinguished from healthy controls and patients with depression or fibromyalgia with significant accuracy.

Comments

These results are consistent with the theory that most patients with strictly-defined CFS are suffering from an ongoing chronic viral infection. (The abnormalities are not limited to recent onset cases; some of those tested had been ill for 19 years). In his editorial on this study, Prof Komaroff speculates about "a chronic low-level 'war' with the immune system attempting in vain to rid the body of infection."

Conversely, the findings do not support the CBT model, which assumes that any infection has gone, that there is no ongoing 'disease' and that the fatigue is perpetuated by psychological factors (like the belief that ME is a physical illness).

However, the study raises several questions.  Firstly, not every patient tested had an upregulated RNase L pathway. Why not? Were they misdiagnosed?  Were they recovering?  Secondly, if the antiviral pathway is activated, why have so few studies identified viruses in patients with CFS? Is the pathway responding to the presence of an infectious agent or is there something wrong with the mechanism that's supposed to switch it off?

Psychiatrists will no doubt wonder whether the abnormalities are the result of chronic stress. If that were the case, one should have observed the same changes in the majority of patients with fibromyalgia which is also a major stressor, like CFS. Still, a study involving patients with 'burn-out' may be interesting.

Future research should also compare CFS patients with people suffering from diseases like hepatitis, to confirm that the abnormalities are related to an ongoing viral infection. Similarly, it might be worth replicating the study using people with broadly-defined CFS (selected using the Oxford criteria). If the definition matters, then fewer of these patients will have the 37 kDa form of RNase L.

To conclude, scientists have found a reproducible enzyme defect which is linked to the health status of patients. However, it's early days so the findings should be regarded as 'preliminary'.

Ablashi, DV et al. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. Journal of Clinical Virology, 2000, 16, 3, 179-191.

HHV-6 is a ubiquitous virus and infection usually occurs in childhood after which it becomes latent.  By measuring certain types of antibodies (e.g. IgG and IgM), one can determine if the virus has been reactivated.

Twenty-one patients with multiple sclerosis (MS) and 35 patients with CFS (CDC criteria '94) were compared with 20 people suffering from other neurological conditions (OND) and 28 healthy blood donors (HD).

In both MS and CFS patients, the researchers found higher levels of HHV-6 IgM and IgG antibody when compared to the healthy controls. IgM antibodies were identified in 57.1% of the CFS patients, 71% of the MS patients, 20% of people with OND and 15% of healthy controls. Moreover, evidence of persistent HHV-6 infection was found in the two CFS patients tested over a period of 2.5 years.

Interestingly, not everyone had been infected by the same strain of the virus. The majority of MS patients were found to have Variant B, whereas the virus identified in CFS patients was predominantly Variant A (70%).

Comment

The significance of these findings remain unclear. Obviously, it supports an organic cause of CFS and suggests certain links with MS. Having said that, the patients with CFS were selected using broad criteria, so patients with post-viral CFS may turn out to have even greater evidence of HHV-6 involvement.

As for the role of HHV-6, we don't know whether the reactivation is the result of another problem, whether HHV-6 is the primary source of infection or whether the virus is responsible for stimulating the immune system. Watch this space!

Friedberg, F et al. Symptom patterns in long-duration chronic fatigue syndrome. Journal of Psychosomatic Research, 2000, 48, 1, 59-68.

This study compared groups with long-duration CFS (median=18 years; n=258) and short-duration CFS (median=3 years; n=28) to a group of healthy 'significant others' (n=79). Data were gathered from a postal questionnaire which included a fatigue scale (Krupp et al 1989) and Brief Symptom Inventory.

Compared with the short-duration CFS group, the long-duration group had significantly higher CFS symptom severity scores, especially for cognitive difficulties, but there was no difference with regard to fatigue, depression, allergies, stress, social support, coping strategies or functional status. The CFS groups differed from the healthy controls in terms of the number of coexisting disorders such as chemical sensitivity, fibromyalgia and cardiac arrhythmias.

The pattern of coexisting disorders in the CFS groups was consistent with the hypersensitivity and viral reactivation hypotheses. The similar rates of fatigue in the short and long duration groups conflicts with the CBT model which predicts increasing fatigue over time.

Iriarte, J et al. Modalities of fatigue in multiple sclerosis: correlation with clinical and biological factors.  Multiple Sclerosis, 2000, 6, 124-130.

The researchers assessed the relationship between fatigue and other symptoms, depression, types of treatment and immune status in 155 patients with MS.

The results suggest that 'fatigue' may not be a single entity. According to Iriarte et al, one can distinguish three different forms, namely asthenia (fatigue at rest), fatiguability (fatigue during or after exertion) and the worsening of other symptoms with exercise (e.g. unsteadiness and blurred vision).

Analysis of the data showed that asthenia was associated with immune activation while fatiguability was linked to abnormalities in the pyramidal tract. (This is a collection of nerve fibres which extend from the cerebral cortex to the spinal cord via the medulla oblongata/brainstem.)

Sleep disorders, anxiety and depression were also a source of fatigue but only in a few patients.

Comment

This study should be replicated using patients with ME!

Copyright EM. Goudsmit 2000. ©
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