CFI Spinal Fluid study from Lipkin and Hornig is out.

Jonathan Edwards

Jonathan Edwards

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Kati said:
What I would like to know is, if the cytokine results are so similar to relapsing-remitting MS patients, what are the chances that patients respond well to at least some of the drugs offered to MS patients and would it be worthwile to explore that route?
@Jonathan Edwards
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I am not sure that the cytokine results are particularly similar to the MS ones. The main similarity is that there is less there than in the controls! That is why I wonder about the controls. I would not be surprised if most people who have enough signs to think they need a lumbar puncture would have raised IL-6 in CSF. IL-6 goes up in all sorts of acute situations. They may not have had infection or haemorrhage but they probably had a nasty headache or something like that - for some reason.

I would not go trying monoclonal antibodies without a much better idea of why. Some of them predispose to very nasty brain disease. The anti-CD40 ligand study had to be stopped because several patients had strokes if I remember rightly.
 
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msf

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Forbin, I realize that was one of the aims of the study, I was just criticizing the idea that they could successfully differentiate the two groups as 'Lyme' or 'CFS' with the screening procedures they used. I wasn't criticizing the idea behind the study so much as the method.
 
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msf

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Yeah, sorry, Giis brought it up and then a few people joined in, so I thought we might as well discuss it here.
 
cigana

cigana

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Forbin said:
The point of the Schutzer study was to look for spinal fluid proteins that were exclusive to the CFS group. 738 proteins were found among the CFS group that were not found in either the Lyme or control group. If there were Lyme cases among the CFS group, they lacked any of the 692 proteins found exclusively among the Lyme group. There were also 305 proteins shared by the Lyme and CFS groups but which were not found in controls.

At any rate, the 738 CFS exclusive proteins represent potential CFS biomarkers. That's what they study was actually looking for. However, because the groups were pooled, there is no way to tell from this study how prevalent any of the proteins were in the CFS group. This phase of the study was never intended to do that. It's purpose was to narrow the field of potential spinal fluid protein biomarkers. Replication of the study could narrow the field further. Once the field is small enough, it becomes practical (by different means) to test individual patients for individual proteins to see which, if any, are consistently - and exclusively - found in CFS patients. A spinal fluid protein(s) found consistently and exclusively in CFS patients would be a biomarker.

This is like looking for a needle in a haystack where the first phase is to rule out 95% of the haystack. That's what the Schutzer study is trying to do. The needle may or may not be in the remaining 5%, but you have just made it a lot easier to look for it.
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OFF TOPIC:
If we're looking for the holy grail of a single common biomarker for "CFS" or for "ME", then the Schutzer study needs to be refined in the way you described.

On the other hand, we already have enough to say whether or not someone has "CFS", since they just need to have any of the 738 unique proteins. We don't necessarily need to look deeper for a common protein (although that would be nice), and in a disease with such heterogeneity it seems the whole concept of "uniqueness" is fundamentally flawed. You could argue the Schutzer study has already found the subgroups we're looking for.
 
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aimossy

aimossy

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I know nothing about cytokines apart from that they are chemical messengers of a sort and involved with the immune system. I am feeling a bit in the dark about what this study really means in general. It shows we are different to healthy controls and what would being low in so many mean. But there seems to be query regarding these controls. I hope some people can explain all the relevance. I have medical knowledge but I am no science guru and lots of people are wondering what this means in a language that they can understand.
 
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lansbergen

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lansbergen said:
TIF is needed for Tcell function

page 330
https://books.google.nl/books?id=s7urXnV1xXsC&pg=PA330&lpg=PA330&dq=lif function&source=bl&ots=3nQ_HJwsZt&sig=iEsdqm3oxOpXzM0s-8PNBa3Wi1E&hl=nl&sa=X&ei=kjEdVe33L47haofKgvgH&ved=
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Neurotransmission
In cultured neuronal cells LIF influences the type of neurotransmitter expressed and induces differentiation into cell types expressing cholinergic transmitter. LIF induces the expression of choline acetyltransferase and represses, among other things, the expression of tyrosine hydroxylase and dopamine beta-hydroxylase. LIF also influences the development of sensory neurons.

http://www.copewithcytokines.de/cope.cgi?key=LIF
 
Snow Leopard

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Jonathan Edwards said:
That is the basic issue. Nobody volunteers for a spinal tap. It seems likely that the cases they used were ill and had taps because someone thought they might have infection or an immune disorder but in the end they did not. The question then is why were they ill? There is also an issue in that the samples would be taken under different conditions and that is the sort of thing that can give rise to systematic shifts in results that could confound their use as controls. There is no simple answer to this I think.
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Some people do (monetary compensation helps), there were so few controls anyway, so I am willing to believe that they were healthy.

The main problem is that the CFS samples were of a different age than the MS/Control samples, potentially processed/stored in a slightly different way too. The samples themselves had been stored for some time and I'm not going to pretend to know the exact consequences of this, but it could affect the results, at least in principle.
 
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Sidereal

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Snow Leopard said:
Some people do (monetary compensation helps), there were so few controls anyway, so I am willing to believe that they were healthy.

The main problem is that the CFS samples were of a different age than the MS/Control samples, potentially processed/stored in a slightly different way too. The samples themselves had been stored for some time and I'm not going to pretend to know the exact consequences of this, but it could affect the results, at least in principle.
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Well, the paper states that controls were being investigated for CNS infection or hemorrhage, suggesting that they were not healthy college students lining up for lumbar puncture in exchange for $£€.
 
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user9876

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Sidereal said:
Well, the paper states that controls were being investigated for CNS infection or hemorrhage, suggesting that they were not healthy college students lining up for lumbar puncture in exchange for $£€.
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It surprises me that there are no standard comparison sets from other trials and that each trial has to test and match controls. Especially when the controls and samples seem to have been collected and stored in different ways.
 
nandixon

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lansbergen said:
LIF seems to be low.

http://en.wikipedia.org/wiki/Leukemia_inhibitory_factor
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Interesting article perhaps:

Leukemia inhibitory factor tips the immune balance towards regulatory T cells in multiple sclerosis.

Authors

Janssens K1, Van den Haute C2, Baekelandt V2, Lucas S3, van Horssen J4, Somers V1, Van Wijmeersch B5, Stinissen P1, Hendriks JJ1, Slaets H1, Hellings N6.

Author information

Brain Behav Immun. 2015 Mar;45:180-8. doi: 10.1016/j.bbi.2014.11.010. Epub 2014 Dec 13.

Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), for which current treatments are unable to prevent disease progression. Based on its neuroprotective and neuroregenerating properties, leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) cytokine family, is proposed as a novel candidate for MS therapy. However, its effect on the autoimmune response remains unclear. In this study, we determined how LIF modulates T cell responses that play a crucial role in the pathogenesis of MS. We demonstrate that expression of the LIF receptor was strongly increased on immune cells of MS patients. LIF treatment potently boosted the number of regulatory T cells (Tregs) in CD4(+) T cells isolated from healthy controls and MS patients with low serum levels of IL-6. Moreover, IL-6 signaling was reduced in the donors that responded to LIF treatment in vitro. Our data together with previous findings revealing that IL-6 inhibits Treg development, suggest an opposing function of LIF and IL-6. In a preclinical animal model of MS we shifted the LIF/IL-6 balance in favor of LIF by CNS-targeted overexpression. This increased the number of Tregs in the CNS during active autoimmune responses and reduced disease symptoms. In conclusion, our data show that LIF downregulates the autoimmune response by enhancing Treg numbers, providing further impetus for the use of LIF as a novel treatment for MS and other autoimmune diseases.
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Snow Leopard

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Sidereal said:
Well, the paper states that controls were being investigated for CNS infection or hemorrhage, suggesting that they were not healthy college students lining up for lumbar puncture in exchange for $£€.
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I should have read the paper in detail before replying!

In that case, I'm afraid to say, that I don't have much confidence in the results of this study in general.
 
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