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Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
it is easy to generate false positives.
I should add the risk of false negatives is also high. Just because some peptide did not get bound by some antibody does not mean the peptide, and especially candidate proteins containing this peptide, are ruled out. As Jonathon first stated here, its the conformation of the peptide (and especially proteins) that is what is bound to by antibodies, and this includes both shape and charge. Linear peptides are weak evidence.
 

RogerBlack

Senior Member
Messages
902
My (limited) understanding is 'linear' may be a misnomer - these are short protein sequences stuck on some glass - they are not flat or held down to the glass rigidly.
They may not be folded as in nature however, and may not be as long, but in some cases you could get legitimate binding.

At the very least, it seems to be an interesting signal, even if it does not directly reflect normal behaviour, it at least seems to correlate well.

Checking longer sequences and finding that the 'natural' extension gives signal, but random ones don't would be another interesting test.
 

anciendaze

Senior Member
Messages
1,841
This research started me thinking about relatively small molecules we commonly ignore. I've mentioned peptide signalling and transcription factors above. A new idea surfaced yesterday, though this is not a direct implication of this research.

Another target of the antibodies found could be protein kinases. While those are typically fairly large molecules, the regions which allow their activity are quite small. They are known to bind ATP to target molecules at sites characterized by a single amino-acid. Serine and threonine are the most common targets, but there are unusual kinases which bind at locations marked by tyrosine. These are now known to be important in the development of cancer, and there are cancer drugs using small molecules which block those binding sites. (Consider Gleevec/imatinib, used against CML.)

From this point on my thoughts amount to speculation. I am thinking about the extraordinary range of evolution covered by organisms which enter a hypometabolic state in response to threats. There must be very general and important threats involved.

Cancer and viruses capable of inducing cancer would be such a threat. I will also note that it is extremely difficult to distinguish "CFS" from the prodromal phase of a number of cancers, particularly leukemias/lymphomas. Inhibiting activity of kinases would be a good response to slow the progression of cancer, it is what our most advanced cancer treatments now do when we know the particular kinase to target. We are only at the beginning of this work, with some 500 or so known kinases in humans. Nature might well have been doing this blindly much earlier.

In most paraneoplastic syndrome patients, where specific antibodies associated with cancer are found, there is no direct evidence of the associated cancer. (Some doctors deny this, but I believe this is a tautology requiring the presence of detectable cancer to qualify as a paraneoplastic disorder.) If the immune response, triggered by whatever cause, is the same as the immune response to an actual cancer several difficult puzzles about this disease would start to make sense.
 

nandixon

Senior Member
Messages
1,092
@anciendaze

I've been having similar thoughts, and I've come to the conclusion that the recent Fluge & Mella study is likely showing that there's an inhibition of the PI3K/Akt/mTOR signaling pathway. This pathway is frequently activated/hijacked in cancer to provide the metabolic needs for the growing cancer.

Where exactly in that pathway (or prior to it) the primary inhibition is occurring is another matter, but an inhibition of the downstream mTORC1 (one of two complexes containing mTOR) - which I think is strongly suggested by the increased expression of SIRT4 found in that study - can seemingly account for virtually all of the primary and secondary symptoms of ME/CFS.

I'll try to make a post on that other thread fairly soon, because there is potentially a simple treatment to help activate mTORC1 and perhaps partially ameliorate some ME/CFS symptoms.
 
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