Journal: J of Chronic Fatigue Syndrome, Vol. 11(2) 2003, pp. 51-69 Authors: Jo Nijs, MSc; Danny Coomans, PhD; Garth L. Nicolson, PhD; Pascale De Becker, PhD; Demanet Christian, MD, PhD; Kenny De Meirleir, MD, PhD
Jo Nijs and Pascale De Becker are affiliated with the Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Belgium.
Danny Coomans is affiliated with the School of Mathematical and Physical Sciences, James Cook University, Australia.
Garth L. Nicolson is affiliated with the Institute for Molecular Medicine, Huntington Beach, CA, USA.
Demanet Christian is affiliated with the Division of Hematology and Immunology, Academic Hospital Vrije Universiteit Brussel, Belgium.
Kenny De Meirleir is affiliated with the Department of Human Physiology, Faculty of Physical Education and Physiotherapy, and the Chronic Fatigue Clinic, Vrije Universiteit Brussel (VUB), Belgium.
Address correspondence to: Jo Nijs, Vakgroep MFYS/Sportgeneeskunde, AZ-VUB KRO-gebouw-l, Laarbeeklaan 101, 1090 Brussel, Belgium (E-mail: mailto:Jo.Nijs@vub.ac.be).
ABSTRACT. An impaired immune system and opportunistic infections are considered important characteristics in the pathophysiology of Chronic Fatigue Syndrome (CFS). Using immunofluorescence we examined healthy subjects (N = 35) and two subsets of CFS patients: those without evidence of Mycoplasma (N = 55) and those with evidence of a Mycoplasma infection in their blood (N = 131). Using monoclonal antibodies and forensic polymerase chain reaction for detection of M. hominis, M. fermentans, M. pneumoniae and M. penetrans, we examined leukocytes in peripheral blood samples.
Both patient groups presented with significantly elevated CD25+ (activated) cells as compared to healthy volunteers. CFS patients without evidence of mycoplasma infection(s) had increased amounts of CD5+ B-cells. Stepwise discriminant analysis indicated the number of activated cells, number of memory CD4+ cells and percentage of suppressor T-cells (lower in Mycoplasma+ patients as compared to Mycoplasma- patients) as the discriminant variables. A classification tree, for predicting the presence of Mycoplasma species in CFS patients, was constructed. Taken together, these data confirm earlier reports on immune activation among CFS patients, but this does not appear to be specific for Mycoplasma-infected CFS patients.
KEYWORDS. Chronic fatigue syndrome, Mycoplasma, immunity, immunofluorescence
Chronic Fatigue Syndrome (CFS), or alternatively Chronic Fatigue Immune Dysfunction Syndrome, is a chronic debilitating disease of unknown cause (1). In such patients Mycoplasma species infections may serve as primary or secondary etiological factors. Mycoplasma are prokaryotes containing circular DNA and some ribosomes (2), lacking a cell wall and certain cellular organelles. The high prevalence of Mycoplasma species infections in CFS has been discussed at length in the scientific literature (3-8).
The presence of opportunistic infections in CFS suggests an impaired immune system in these patients. Indeed, a deregulated 2'5' oligoadenylate synthetase ribonuclease antiviral pathway (9-11) and a reduced natural killer cell function (13-15) are two characteristics of impaired immunity in at least subsets of CFS patients. Although some Mycoplasma species are part of the normal human flora, others are capable of causing complex systemic infections in immunocompromised hosts, as seen in HIV-AIDS (16) and CFS (3-7).
The immunological properties of Mycoplasma species have been studied extensively. M. fermentans has been shown to affect the immune system via T – or B-cell activation and macrophage stimulation [reviewed in (2)]. A membrane-associated complement C3-activating protein (M161Ag), from M. fermentans, efficiently promotes the production of nitric oxide (NO), interleukin I beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-10 and IL-6 in human peripheral blood monocytes (2,17-19). Activation of the complement system by C3 in M.fermentans-infected cells in turn stimulates the release of C5a chemotactic factor and enhances phagocytic activity. Kikkawa et al. (17) have demonstrated that the human complement system was able to clear M. fermentans from the surface of infected human cells, but was not able to prevent persisting low-grade infections in human tumour cell lines, probably due to rapid invasion of the infected cells into tissues.
There are some data available that describe host defence action against respiratory mycoplasmosis caused by M. pneumoniae and M. pulmonis. Both innate (mediated by alveolar macrophages) and humoral immunity appear to be of prime importance in the defence action against these Mycoplasma infections (20). Moreover, T-cell responses in respiratory Mycoplasma infections can result in exacerbation of lung lesions, whereas innate immunity is crucial in defence of the lungs and humoral immunity in preventing dissemination of infection to extrapulmonary sites (20). In accordance with these observations, a recent report provides an explanation for the characteristic chronic nature of Mycoplasma spp. infections.
In this report M. pulmonis infection induced a transitional shift of the TH-I (T helper cells type 1)- TH-2 balance in favour of humoral immunity, which is thought to allow the microorganism to survive (21). The exact role of cell-mediated immunity in Mycoplasma infections, however, remains to be established.
To our knowledge, the possible effects of Mycoplasma species on immune cells in CFS patients have not been examined. Therefore, we examined CFS patients with or without Mycoplasma infection(s) and healthy volunteers to see if certain immune patterns were characteristic of chronic infections in these patients.
© 2003 by The Haworth Press, Inc. All rights reserved. (Received via Co-Cure.)