A Guide to RNase L in Chronic Fatigue Syndrome (ME/CFS): Breathing Difficulties

Nijs, J., De Becker, P., De MeirLeir, K., Demanet, C., Vincken, W., Schuernans, D. and N. McGregor. 2003. Associations between bronchial hyperresponsiveness and immune cell parameters in Chronic Fatigue Syndrome, Chest 123: 998-1007.

This study examined what part of the immune system is dysfunctional in a malady CFS patients often experience: bronchial hyperresponsiveness. Bronchial hyperresponsiveness (BHR) occurs when exaggerated responses to small amounts of non-allergenic substances cause the smooth muscles in the lungs to constrict thus making it difficult to take deep breaths. BHR also occurs in asthma and several other pulmonary diseases.

(Why is it important to determine the origin of this problem? Aside from the direct aid that may accrue to patients it helps pin down the kind of immune dysfunction occurring in CFS. That is still in question.)

The study indicated that the BHR seen in CFS patients does not originate in the inflammatory response found in asthmatics that involves IgE activation of mast cells and eosinophils. Thus it does not appear to be a response to extracellular antigens, bacteria or toxins. Instead CFS patients with BHR had higher numbers of cytotoxic T-cells – which attack cells infected with intracellular pathogens – and lower numbers of naïve T-cells. (I believe that the lower numbers of naïve T-cells suggests that undifferentiated T-cells are rapidly being turned into mature T-cells in order to fight an ongoing infection.) This suggests that antigens produced by intracellular pathogens such as cytomegalovirus (CMV), adenovirus or mycoplasma residing in the lungs of CFS patients may be inducing a prolonged hypersensitivity response (DTH). The authors note, however, that CD4+ T-cells (helper cells), not the CD8+ (cytotoxic) T cells seen in this study, are usually activated in the DTH response.

Because RNase L fragmentation was, interestingly enough, not enhanced in CFS patients with BHR, it does not appear that the BHR response has its origin in RNase L dysfunction. The authors noted, however, that other key parameters of RNase L dysfunction were not measured in this study.

Given elastase’s role in many chronic pulmonary diseases and its putative role in RNase L fragmentation, one can speculate that the authors expected to find that CFS patients with BHR exhibited higher numbers of (elastase producing) phagocytic cells (neutrophils, monocytes, macrophages, ) than did CFS patients without BHR. This was, however, not found. Elastase was not measured in this study.

In summary the BHR found in CFS patients does not appear to be the result of an inflammatory response consisting of IgE activation of mast cells and eosinophils. Instead it appears to originate in a response of cytotoxic T-cells to intracellular invaders. Further research will be necessary to elucidate the precise mechanisms involved.

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