LiveAgain
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I've had NK function tested twice and it comes back within normal range. I keep reading that low NK function is typical in ME/CFS. So what if you test normal? Anyone else?
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I've had NK function tested twice and it comes back within normal range. I keep reading that low NK function is typical in ME/CFS. So what if you test normal? Anyone else?
We appreciate the interest of Marques et al. in the assessment of immune parameters in Lyme disease. The conclusions of their report (2) appear to differ from the findings of our study of CD3− CD57+natural killer (NK) cells in patients with persistent symptoms of tick-borne illness (3). Further scrutiny reveals that their analysis employed questionable patient selection criteria and unproven testing and ultimately lacked the power to detect the differences observed in our study.
The two reports have little in common. Our study examined 73 patients with a female/male ratio of 1.6:1, consistent with the gender distribution of patients with chronic Lyme disease (1, 5). Using a flow cytometry test system with an established normal range and well-defined coefficient of variation, we found that the CD3− C57+ NK subset appears to be a useful immunologic marker in patients with persistent Lyme disease symptoms compared to either normal subjects or 32 disease controls (3). Importantly, factors that appeared to influence the CD57 NK levels were the predominant type of Lyme symptom and response to antibiotic treatment on serial sampling (3).
Recent research showed it was a specific nk cell called nk bright cells which function poorly, also cd8 t cells function poorly, that could be a possibility??
Was your CD57 normal before or after undergoing treatment for Lyme?I don't have suppressed NK cells and I've been diagnosed with Lyme as well.
Ema
I'm not sure if this is what you're referring to, but the information might be useful either way. This is from a thread Rich started last year:I'm talking about NK function. This is the test I had done:
http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=34184X&labCode=QDV
I just keep reading over and over that most people with ME/CFS have low NK function.
Natural killer cells normally kill cells that are infected with viruses. They do this by secreting a substance called perforin, which makes a hole in the cell membrane, and then injecting granzymes, which induce the cell to undergo apoptosis (programmed cell death). The CD8 cytotoxic T cells operate in the same way in terms of their killing mechanism.
Some years ago, Dr. Kevin Maher, who was in Dr. Nancy Klimas's group, reported that the natural killer cells in PWMEs are low in perforin. It was also found that the CD8 cytoxic T lymphocytes were also low in perforin. This would, of course, inhibit their cytotoxic activity.
I suggest that this new result is consistent with the mechanism I have proposed for low perforin in ME/CFS. It indicates that the NK cells and CD8 cells are "trying hard" to produce perforin by boosting the transcription of the PRF1 gene to messenger RNA, but the protein synthesis process is at least partially blocked and cannot respond. If glutathione is somewhat depleted in the NK cells and CD8 cells, the protein synthesis process would indeed be partially blocked.
I continue to propose, as I did in 2007, that other features of the observed immune dysfunction in ME/CFS can also be explained by the GD-MCB hypothesis. These include the shift to Th2 immune response, the elevated RNase-L and formation of the low-molecular-weight RNase-L, the elevated inflammation, the failure of lymphocytes to proliferate when stimulated with mitogens, the reactivation of viruses and intracellular bacteria, and the accumulation of pathogens over time.
So first, how does the immune system normally respond to viral infections? There are basically four types of responses, listed here in roughly the chronological order in which they normally occur:
1. Type I interferon (interferons alpha and beta) responses
2. Natural killer cell response
3. Virus-specific cytotoxic T lymphocyte (CD-8 "killer" T cell) response.
4. Antibody response
Type I interferons are secreted by infected cells, to alert nearby cells, and hopefully prevent them from becoming infected. The Interferon responses include the PKR, the 2,5-OAS RNase-L, and the Mx responses, among others. The PKR response inhibits the synthesis of viral proteins inside host cells. The 2,5-OAS RNase-L response degrades viral RNA inside host cells. The Mx response inhibits viral gene expression and assembly of the virions inside host cells.
The natural killer cells recognize virally infected cells in which the viruses are attempting to hide from the immune system by shutting off the Class I HLA mechanism that the CD-8 cells use to recognize virally infected cells. If the Class I HLA molecules are not displayed on the cell surface, the NK cell kills the cell.
The CD-8 killer T cells kill cells that are displaying viral antigens by means of the Class I HLA molecules.
Antibodies against viral antigens are made by B lymphocytes and plasma cells, and they bind to viruses that are outside the host cells, as when an infection is beginning or when viruses are spreading from one host cell to another.
This neutralizes the viruses, so that they cannot enter new host cells, and it can also "mark" them for attack by other cells of the immune system, such as macrophages.
O.K., now what happens to these responses in ME/CFS?
Well, the Type I interferon responses continue to work, and even though they are intended to be short term responses to hold back the viral infection until the "cavalry" in the form of the CD-8 killer cells arrives, and the CD-8 cells, together with the NK cells, knock out the viral infection, in ME/CFS the interferon responses continue to work overtime (and even become dysregulated in the case of the RNase-L) because the CD-8 killer cells are not able to take over. Sadly, the "cavalry" never arrives, leaving the "civilians" to battle the "Indians" in an ongoing guerrilla war.
What causes the formation of the dysregulated low-molecular-weight RNase-L molecules? I propose that glutathione depletion is responsible. It activates calpain, and calpain cleaves the normal RNase-L molecules. The cleaved parts join together, forming the unregulated LMW RNase-L.
Both the NK cells and the CD-8 killer T cells are rendered impotent by their inability to make perforin and granzymes in normal amounts. Furthermore, the CD-8 killer T cells are not able to multiply to outnumber the "bad guys" as they should. Why does this happen? I propose that it is a result of glutathione depletion and depletion of folates, respectively, which are part of the GD-MCB vicious circle mechanism that I believe is at the basis of the pathogenesis of ME/CFS.
Antibody production continues, and in fact may be increased, because of the shift toward the Th2 immune response in ME/CFS, which favors humoral immunity, i.e. the production of antibodies by B lymphocytes and plasma cells. What causes this shift? Again, I have proposed that glutathione depletion is responsible, in this case in the "naive" T cells.
So what we have are heightened interferon and antibody responses, but failure of the main "kill" mechanisms. The result is that latent viruses in the body (such as EBV, CMV and HHV6) are able to reactivate, and the immune system continues to fight with the weapons it has left, confining the viruses and keeping the host alive, but not winning the war against the viruses by completely knocking them out or putting them back into latency.
Now, what about your questions?
Would interferon treatment work? Well, to some degree, but without the other dysfunctional immune responses to help them, they cannot completely knock out the viruses.
Why don't PWMEs get colds and flus? I think it's because of the constantly elevated interferon responses. This produces what has been called the "antiviral state." With this going on, it's difficult for a newly introduced virus to get a foothold.
Does this have anything to do with the elevated cytokines in ME/CFS? Yes. The immune system is well aware that there are enemies inside the perimeter, and it is sounding the alarm, trying to organize the defense. The cells of the immune system are sending chemical messages back and forth to each other in the form of cytokines. However, because the NK cells and the CD-8 cells are impotent, even though the trumpet sounds, they don't respond, because they are not able to, so the messages just keep flying back and forth, unheeded.
So what's the solution to this problem? How do we win the war? Well, I'm still working on that, but I think that a big part of it will be to restore glutathione, folates and methylation, and that will probably require a methylation protocol.
Beyond that, because viruses that are well-entrenched have various ways of foiling the immune system, even though the immune system is restored, other measures will likely also be needed. One interesting one is GcMAF, which overcomes one of the strategies used by viruses to foil the immune system, i.e. nagalase. Antivirals are another possibility, especially in view of some success using them, as in Dr. Lerner's experience.
I hope this is helpful.
Best regards,
Rich
Lotus97Was your CD57 normal before or after undergoing treatment for Lyme?
You understand this a lot better than I do. The reason I asked is because I thought maybe your CD57 would be low before treatment, but normal after treatment since the Lyme bacteria is supposed to lower CD57. Do you think the information is wrong about people with Lyme having low CD57? I'm confused by those conflicting studies I posted earlier. I decided to start the Buhner protocol and part of the reason he recommends cat's claw is because it's supposed to raise CD57.Lotus97
These are the results I have below.
I was told they were high but maybe you will see something different!
2009 (well before Lyme treatment/diagnosis but after onset of severe relapse)
Natural Killer Cell Profile
%CD2 75 (74-92)
%CD3 76 (61-89)
%CD5 85 (62-89)
%CD7 73 (65-94)
%CD8 12 (10-47)
%CD16 20 (2-21)
%CD56 25 (4-29)
%CD57 12 (4-37)
Then I have this HNK1 (CD57) Panel from Labcorp:
%CD8-/CD57+ 7 (2-17)
Abs CD8-CD57+ Lymphs 196 (60-360)
This was done about 4 months after Lyme diagnosis and into treatment.
Ema
Hi, I'm in my 4th month of Bartonella treatment. Now taking rifampicin 600mg one dose and 100mg Minocyclin. So far no response. I don't have even stupid Herx. I'm visiting KDM in 2 weeks. He told me I need at least 4 months to see if it's working.
Also after 2 months of treatment my CD57 count drop from 58 (oct2012) to 35 (60 being laboratory range). It should go the other way they say when Lyme is involved and treated. Do your doctors checking your CD57 count? Do you notice any correlation with your treatment?
I am mostly homebound and have NORMAl, healthy NK Function. Super low NK number though. Klimas studied those with and without healthy NK function. So much to learn about the immune system.I've had NK function tested twice and it comes back within normal range. I keep reading that low NK function is typical in ME/CFS. So what if you test normal? Anyone else?