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CFS: RNase L

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Hi everyone. i am looking for anyone who has had their RNase L levels tested, what it was, if it changed with treatment, and if there was any correlation with clinical improvment.

My RNase L was 1885 (normal: <50) before treatment and is now normalizing on antivirals. However, I am not experiening much in the way of clinical improvement (yet?).

Thank you


New Member
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.




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.


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!



New Member
I don't know what to think of this test. One of my RNase L tests was normal but I'm housebound with fatigue!

My doctor said he didn't believe the test as he believes that viruses are at the root of my illness.

It seems that the test just doesn't correlate with a person's level of feeling well.

I'm curious to see how Dr. Montoya talks about it in his paper. Didn't people in the study have there RNase L tested?
yes people in the study had the rnase l tested but i do not think he found a correlation.

heap..thank you...i did have all bacterial tests and many other tests too...

i hope you all are doing well.



New Member
ladybug, sometimes bacterial infections like mycoplasma etc dont show up in tests, sometimes its worth a trial of doxy and see how u go.
good luck
thanks again. i did try doxy for a month or two and it had no effects at all, either positive or negative.....

i am so sure my condition is viral, but just don't know the best way to attack it.

dr. lerner is the best but he seems to want only valtrex and valcyte. i want to be able to take other meds to try to make day-to-day living more bareable, such as maybe cortisol or something, but he won't hear of it.

i am too scared to leave dr. lerner though, as he is the one with 25 years' experience with antivirals.

i am very intrigued by artesunate, which seems to be great for HHV6 and not toxic. but it is not available in north america.



New Member
Cortisol can be a nasty drug(osteoporosis,immune depressant etc), i would be tempted to leave it as a last resort. If your paying big money to see dr lerner and he advises antivirals, i think you should take his advise or see someone else, he's the man when it comes to antivirals. i think you have nothing to lose, valtrex is quite safe long term.

Google immunovir/imunovir this can be helpful for viral infections too. An aussie doc says that immunovir isnt much different to the amino acid version called inosine which u can buy cheaply at health food shop. I had some success with it for a few months then stopped, but apparently when using it u cycle off and on every few months. not a cure but can give u a few months every year of some improvement.

havent hears of artesunate will look into it, thanks.
thank you. yes...i will stay with dr. lerner as long as i can afford it, which might be maybe a year or so.

please keep in touch



ladybug, others
I got back the results of my test today, interesting--super high rnase stuff, unremarkable interleukin and positive immunobilan:

elastase =3285 (normal is below 140!)
rnaa= 149 (norm < 50)
rnap=21.3 (<2 n)
and a lot of the iga stuff was extremely high and igm high
I dont really have much of a clue what this all means yet.
my regular local doc is just starting to explore these issues but isnt expert in it like peterson etc and he isnt sure how much stock he put in it, but did say if the theory is correct it could sure correlate with my fatigue. the interesting thing is i have chronic pain and i guess the interleukin stuff is more indicative of inflammation which i was low on so could explain why antiinflammatories do jack for my spinal pain.

his interp of this indicates more antibiotics vs antivirals, so i am confused ladybug what makes one focus more on one than the other, but he suspected possible bacterial infection of some sort if something from these results. we are going to do more research before do any abx and have me work even more on my gut with more suppplementation. i have already been doing probiotics and some herbs etc and helps some, but obviously not enough to get thse results down. I have had cfs for almost 20 years. If anyone is interestd i can list a supplement for gut he rec'd. I also am going to consult with a cfs expert on this later this year.
He thought it was sort of odd to have high rnase but low interleukin. i dunno, a lot of this is over my head.
[This Message was Edited on 02/09/2009]
simon thanks for posting your results!

which interleukin was low? there are many types (IL-2, IL-6, etc)

your doc is not bad! it is more likely that if you had active virus, your RNase L would be much higher (mine was almost 2000!) your RNase L is in keeping with bacteria.

the RNAP is high like mine; i suspect that this has something to do with the inflammation you have a lot of, cuz of the very high elastase. i think this ratio becomes more and more abnormal the longer you have been sick since the normal RNase L is cleaved and you are left with a lot of LMW RNase L.

unfortunately, i do not know much about immunobilin but if i had to guess, i would say your doctor might well be right about the bacteria and gut issues.

best of luck and please keep us posted!!!!



ifng=18.8 (17n)
il10 <24 (<85)
il12 79.8 (<240)
il1b 39.1 (<192)
IL2 <24 (<46)
IL4 <33 (<33)
IL6 <14 (<14)

yea the local doc is cool, nice to see someone in mainstream system open to doing the testing
hi simon. i have been trying to find the differences between the cytokine profiles (IL's) of someone infected with virus and someone infected with bacteria but am having no luck!

perhaps someone else could help...?



dont stress on it sue
i have been dealing with this stuff for so long i feel nonchalant, sort of, about figuering it out
cus there is no big solution anyway......
will let ya know if i learn more
if others come along that can shed light please do


nkc1: 3.53 (L) range= 6-20%
nkc2: 0.3 (L) range 6-20
nkc3: 0.7 L r= 3-33
nkc4 88.10 H r= 45-76
nkc5 1570 N r= 750-2310
nkc6 60 L r= 120-410
nkc9 L r= 8-170

does this mean anything to you sue or others?
i have never seen this test before!

my advice is to call redlabs and ask to speak to craig. ask him to please quickly explain what the test indicates or where to look to find out. if he cannot help, ask to leave a message for dr. vincent lombardi. if he doesn't call back in a few days, call again. you have to be persistent. tell them you are not looking for medical advice, just where to find out more information about the test. tell them your doctor doesn't know either...just keep bothering them until someone agrees to interpret the results. it worked for me.
[This Message was Edited on 02/13/2009]


New Member
Here are my Redlabs test results for January 2008 and January 2009. The Jan 2008 is shown first, then the Jan 2009.

Background: I have had CFS for 18 years starting with a severe case of mono at age 23. I fluctuated btw 70 and 80% of normal for most of the time until 2 years ago when I had a very bad relapse that left me at about 30% of normal. Over the time frame btw the two tests (the last year) I have done many treatments including among other things, taking Famvir (500mg x2) for the entire year, starting Martin Pall/Ziem protocol about 6 months ago, daily FIR sauna, etc. I have gotten some clinical improvement and now probably 40-50% of normal.

Jan 08 vs Jan 09
elas: 92 vs 686 (r= <140) – went from normal to very high
rnaa: 657 vs 25 (r= < 50) – went from very high to normal
rnap: 0.1 vs 20.9 (r= <2) -- went from normal to very high

As you can see there was a radical change over the last year, which does make me wonder about the reliability of these tests.

nkc1: 3.4 vs 9.9 (r= 6-20)
nkc2: 4.4 vs 3.6 (r= 6-20)
nkc3: 13.1 vs 3.6 (r= 3-33)
nkc4: 75.5 vs 81.9 (r= 45-76)
nkc5: 1230 vs 750 (r= 750-2310)
nkc6: 60 vs 90 (r= 120-410)
nkc9: 3 vs 3 (r= 8-170)

This test is only for Jan 2009:

Immunobilan (<2.0 = normal, 2.0-3.0 = high range, >3.0 = extreme positive)

Kleb 6.01
Proteus 4.62
Citrobacter 4.71
Psuedomonas A 3.97
Psuedomonas P 3.52
Morganella 3.62
Hafnia 4.92

All less than 2.0

Note my recent CDSA tests (Genova, Metametrix) do not show a major problem with pathogenic bacteria (though several years ago the CDSAs did show major problems and I did treat them, but did not feel any better).
mulder...after antiviral therapy, my RNase L activity (RNAA) also dramatically improved but the ratio (RNAP) and elastase increased just like yours.

i am not sure what the increase in elastase means but i suspect the LMW RNase L levels will normalize over time. k. loomis told me that elastase does seem to increase during treatment but she wasn't sure why either.

perhaps i will ask prof. sudaholnik when i get a chance.