RNase L and Chronic Fatigue Syndrome (ME/CFS): A SCREENING TEST?

Roelens, C., Herst,C.V., D’Haese, A., De Smet, K., Fremont, M., De MeirLeir, K. and P. Englebienne. 2001 G-actin Cleavage Parallels 2-5A Dependent RNase L Cleavage in Peripheral Blood Mononuclear Cells – Relevance to a Possible Serum-Based Screening Test for Dysregulations in the 2-5A Pathway. 2001. Journal of Chronic Fatigue Syndrome 8 (3/4): 63-82.

The G-actin protein is a central component of the cells superskeleton. Actin plays a role not only in intracellular organization but also in antigen presentation and T-cell signaling. (See Chapter VI of “Chronic Fatigue Syndrome: A Biological Approach”.).

G-actin fragments are typically released into the serum when cells are broken up into small bits during cell apoptosis. Depending on the degree of RNase L fragmentation found apoptosis rates can either be increased or decreased in CFS. The abnormal levels of apoptosis seen in CFS patients could be due to RNase L dysfunction or to an upregulated protein kinase R enzyme or both.

In order to determine if the RNase L fragmentation occurring in CFS patients was accompanied by increased G-actin fragmentation the researchers first screened the PBMC’s (peripheral blood mononuclear cells) of CFS patients for two of the terminal ends (N @ C) of the G-actin protein. Both were found.

A further analysis indicated that the abundance of the N-terminal section of the G-actin in serum was highly correlated with the degree of RNase L fragmentation. When the addition of calpain to PBMC’s to RNase L generated the same 37-kDa fragment seen in CFS patients, it appeared that calpain was responsible.

A further test of calpain and caspase inhibitors indicated that only calpain was involved in RNase L fragmentation. (Because calpain is involved in apoptosis this suggests that RNase L fragmentation is a function of increased apoptosis. Since both branches of the IFN immune response dysregulated in CFS – protein kinase R (PKR) and RNase L – are involved in apoptosis either could be responsible.)

The authors noted that the testing for the 37-kDa fragment is expensive (and requires a lot of blood!) and suggest that a test for the N-terminal section of the G-actin fragment would be an appropriate screening technique. (This would be quite a breakthrough. However, despite the low cost of this test and the need for a cost-effective means of screening for CFS patients, no studies have attempted to confirm this finding in the four years since its publication)

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