2001 Clinical and Scientific Meeting

J Nijs1, 3, PT; K De Meirleir1,2, MD, PhD; D Coomans3, PhD; P De Becker1, PhD; GL Nicolson4, PhD

Department of Human Physiology
Faculty of Physical Education and Physical Therapy
Vrije Universiteit Brussel,

Chronic Fatigue Clinic
Vrije Universiteit Brussel Department of Biostatistics
James Cook University

Institute for Molecular Medicine,
Huntington Beach,

To whom correspondence should be addressed:
Vakgroep MFYS,
AZ-VUB KRO gebouw ­1,
Laarbeeklaan 101,
1090 Brussel

Associations between Mycoplasmae and 2,5A synthetase RNase L antiviral pathway in Chronic Fatigue Syndrome

Numerous reports highlighted the importance of Mycoplasmae spp. [1 - 6] and the deregulation of the 2.5A synthetase RNase L antiviral pathway [9 - 14] in subsets of Chronic Fatigue Syndrome (CFS). We hypothesised there may be a co-morbid physiopathological mechanism between infection by Mycoplasma species and the deregulation of the 2,5A synthetase / RNase L antiviral pathway in Chronic Fatigue Syndrome. The study was conducted in Brussels, at a university-based outpatient clinic (Vrije Universiteit Brussel). We enrolled 192 consecutive patients seeking care for prolonged fatigue as major complaint between the first of January and the end of June 1999, who complied with the Fukuda et al [7] definition. All subjects had to be free of antibiotic-treatment two months prior to blood collection. Mycoplasmae-infected CFS-patients presented with significantly elevated RNase L-ratio, compared to non-infected subjects. These results suggest a strong interaction between Mycoplasmae infections and a deregulation of the 2,5A synthetase RNase L antiviral pathway. Indeed, Mycoplasmae are active in stimulating several components of the immune system. They can act as polyclonal T-cell and B-cell activators [17], and some Myoplasmas can trigger macrophages in vitro [15]. To bring about their phagocytic activity, monocytes produce elastase. The latter enables them to pass through connective tissues. Elastase is capable of cleaving 80 kDa RNase L [16], thus causing deregulation of the antiviral pathway. In addition, low molecular weight RNase L has been suggested to reduce TH1 activity [8]. The latter implicates an increased susceptibility to infections and a suppressed ability to eliminate intracellular antigens.


1. NASRALLA MY, HAIER J, NICOLSON NL, NICOLSON GL. Examination of Mycoplasmas in blood of 565 chronic illness patients by polymerase chain reaction. In J Med Biol Environ 2000; 28(1): 15-23
2. NASRALLA M, HAIER J, NICOLSON GL. Multiple Mycoplasmal infections detected in blood of patients with Chronic Fatigue Syndrome and / or Fibromyalgia. Eur J Clin Microbiol Infect Dis 1999; 18: 859-865
3. NICOLSON GL, NASRALLA MY et al. Role of Mycoplasmal infections in Fatigue Illnesses: Chronic Fatigue and Fibromylagia Syndromes, Gulf War Illness and Rheumatoid Arthritis. Journal of Chronic Fatigue Syndrome 2000; 6(3/4): 23-39
4. NICOLSON GL, NICOLSON NL. Diagnosis and treatment of Mycoplamsmal infections in Persian Gulf War Illness - CFIDS patients. International journal of occupational medicine, immunology and toxicology 1996; 5:67-78
5. VOJDANI A, FRANCO AB. Multiplex PCR for the detection of Mycoplasma fermentans, M hominis, and M penetrans in patients with Chronic Fatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis, and Gulf War Syndrome. Journal of Chronic Fatigue Syndrome 1999; _:187-197
6. NICOLSON GL, NASRALLA M et al. Diagnosis and treatment of chronic mycoplasmal infections in fibromylagia and chronic fatigue syndromes: relationship to gulf war illness. Biomedical Therpay 1998; 16(4): 266-271
7. FUKUDA K, STRAUSS SE et al. The Chronic Fatigue Syndrome, a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953-959
8. ROELENS S, HERST CV, DE SMET K, D'HAENE A, DE MEIRLEIR K, ENGLEBIENNE P. Apoptotic dysfunction consecutive to RNase L cleavage is likely to be central to the maintenance of chronic fatigue syndrome. Abstractbook Fifth International Research, Clinical and Patient Conference of the American Association for Chronic Fatigue Syndrome, January 26-29, 2001; p70
9. SUHADOLNIK RJ REICHENBACH NL et al. Upregulation of the 2-5A synthetase/Rnase L antiviral pathway associated with chronic fatigue syndrome. Clinical Infectious diseases 1994; 18(S1): S96-104
10. SUHADOLNIK RJ, PETERSON DL et al. Biochemical dysregulation of the 2-5A synthetase/Rnase L antiviral defense pathway in chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome 1999; 5(3/4): 223-242
11. DE MEIRLEIR K, BISBAL C, CAMPINE I, DE BECKER P, SALEHZADA T, DEMETTRE E, LEBLEU B. A 37 kDa 2-5A binding protein as a potential biochemical marker for Chronic Fatigue Syndrome. The American Journal of Medicine 2000 ; 108 : 99-105
12. SUHADOLNIK RJ, PETERSON DL et al. Biochemical Evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. Journal of Interferon and cytokine research 1997; 17:377-385
13. BISBAL C, MARTINAND C et al. Cloning and Characterization of a Rnase L inhibitor. The Journal of Biological Chemistry 1995; 270(22):13308-13317
14. MARTINAND C, MONTAVON C et al. Rnase L inhibitor is induced during human immunodeficiency virus type 1 infection and down regulates the 2-5A/Rnase L Pathway in Human T Cells. Journal of Virology 1999; 73(1): 290-296
15. BAUM SC. Mycoplasma pneumoniae and atypical pneumonia. Part III, section D:161 in MANDELL GL, BENNETT JE, DOLIN R. Principles and practice of infectious diseases. New York: Chirchill Livingstone 1995; 1713-1718
16. HERST CV, DE SMET K, D'HAESE A, et al. The interaction of RNase L ankyrin domain with ABC transportres might explain pain and many of the physiological disorders of CFS. Abstract presented at the AACFS fifth international research, clinical and patients conference. Abstract book page 71
17. SIMECKA JW, ROSS SE, CASSELL GH, DAVIS JK. Interactions of Mycoplasmas with B cells: antibody production and non-specific effects. Clinical Infectious Diseases 1993; 17(S1): S176-82


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