The immune system abnormalities mimic the immune pattern seen in viral infections. Specific findings include increased nuMEs of activated cytotoxic T cells, low natural killer cell function, and elevated immune complexes. A large University of Miami study found that the array of immunological defects suggest that ME/CFS is a form of acquired immunodefficiency.
A more specific immune system abnormality has been discovered in ME/CFS of increased activity and dysfunction of the 2-5A RNase-L antiviral pathway in lymphocytes. The dysregulation of the RNase-L pathway supports the hypothesis that viral infection may play a role in the pathogenesis of the
illness. Patients with ME/CFS were very different from patients with major depression, fibromyalgia or healthy controls.
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RNASE L CLEAVAGE ASSAY (Code: RNAE)
Background
Ribonuclease L (RNase L) is one of the key enzymes induced by interferon and is responsible for many of the anti-viral effects observed. The native RNase L has a molecular weight of 80 kDa and is activated by binding a small effector molecule known as 2-5A. Once activated, RNase L destroys viral RNA (stopping the infectious process) and at the same time triggers the removal of infected cells by inducing programmed cell death (apoptosis).
In the immune cells of CFS patients, RNase L is cleaved by the action of proteases. Once cleaved, the lower molecular weight (LMW) species of RNase L lack the regulatory functions to control them and as a result, cellular RNA is cleaved at an accelerated rate. In addition, some of the RNase L fragments formed upon cleavage can disrupt cellular ion fluxes, accounting for many of the physiological symptoms of CFS.
Method
Radiolabeled ligand-receptor assay. Radiolabeled 2-5A is bound to the enzyme in cellular extracts, and the amounts of different 2-5A binding proteins (native or LMW forms of RNase L) are quantified following gel electrophoresis.
Result, normal range
Quantitative. The increased presence of lower molecular weight forms indicates a progressively disrupted and dysfunctional immune system. The reported value corresponds to the ratio of LMW form to the native 80 kDa form; this ratio is useful to classify the disease and monitor its progression. Ratios over 0.5 are considered positive.
One Answer to the mysterious disease syndrome variously known as M.E. (Myalgic Encephalomyelitis), CFS (Chronic Fatigue Syndrome), or CFIDS (Chronic Fatigue and Immune Dysfunction Syndrome) may be found in a newly discovered condition called The Rnase-L Defect. I have M.E., and I have the Rnase-L Defect. Join me in the quest to learn more about this serious condition.
In 1995, Temple biochemist Robert Suhadolnik, Ph.D., discovered a new immune defect in the 2'-5'A Synthetate Antiviral Pathway. When the body confronts a virus, a biochemical process creates an enzyme called Rnase-L. Suhadolik discovered that patients from the Peterson-Cheney practice in Incline Village, NV, who had fallen ill with a mysterious, debilitating disease in the mid-1980s, did not have normal Rnase-L. Instead, they produced a half-sized RNase-L protein - when viewed using electronmicroscopy, the Rnase-L was literally blank for half the space. The same year, unaware of Dr. Suhadolnik's finding, two French researchers, Bernard Le Bleu and Catherine Bisbal, also discovered that patients with the same symptoms had defective Rnase-L. Instead of weighing 80 kDa like normal Rnase-L, it only weighed 37kDA - again, roughly half the normal size. This is where the name that is often used comes from: the 37kDA Rnase-L, or the low molecular weight (LMW) Rnase-L. Having the finding duplicated on the other side of the globe using a completely different method was a very strong sign that both Suhadolnik and the Le Bleu-Bisbal team had made a significant new scientific finding.
Patients with the RNase-L Defect overproduce normal Rnase-L, which then degrades into the 37kDa version. Research by Dr. Susan Horvath, at Temple with Suhadolnik, has shown that the in these patients, the 80kDA protein cleaves into three parts. The middle drops out, and the first and third parts bind into the new, 37kDA Rnase-L protein. This leads to several problems. The defective 37kDa protein leaves the body without its normal antiviral defenses. Patients suffer from the reactivation of viruses that should be dormant. In my own case, that has meant recurring bouts of Epstein-Barr, and a chronically active case of HHV-6, Variant A, when the 37kDa Rnase-L is not under control. There may be other chronically activated or reactivated viruses - these were the only two we ever tested for. Patients diagnosed with "Chronic Fatigue Syndrome" would actually have "Chronic Viral Re-activation Syndrome". Most doctors would not pick this up, because the usual test given is an antibody screen. Once you have had the virus, you will always test positive for the antibody screen. Hence, it is difficult to tell whether a patient currently has the virus or not, and it is difficult to distinguish between those who easily disposed of the virus years ago, and those who continue to fight it.
The "rogue" protein that drops out of the 80kDa when it degrades to 37kDa itself causes problems within the body. It can cause an up-regulated immune system that fights the wrong enemy, which would explain why many patients with this disease also suffer from such diseases as fibnromyalgia and Hashimoto's thyroiditis (I have both). Another problem that it causes has been named "channelopathy". Ion channel disruption has been known to cause, among other things, increased pain, night sweats, muscle weakness and vision problems.
Hi ladybug,
Some info I have found. From what i can gather RNase is suppose to be an indication of a virus, if tested positive (antibodies)to ebv etc and have high RNase then it is 'probably reactivating"?
I am wondering if you have a bacterial co-infection (mycoplasma or chlamydia pnuemonia)as your RNase have dropped from the antivirals but you still feel unwell. Have you been tested for bacterial infections although they are unreliable, Maybe you need to trial some doxycycline along with your antivirals, low dose pulsing every second day and see how you go.
Good luck cheers!
