The best evidence yet that immune system problems can cause ME/CFS? Simon M blog

Simon M

Simon M

Senior Member (Voting Rights)
The best evidence yet that immune system problems can cause ME/CFS?

Human leucocytes Antigen (HLA) proteins play an essential role in helping the immune system to recognise pathogens. This new research is easily the best study yet of HLA alleles (gene variants) in ME/CFS. It finds links between alleles of at least two HLA genes and ME/CFS. And since the illness can’t change (HLA) DNA, the link must be that the alleles must play a causal role in ME/CFS. So this evidence that the immune system plays a causal role for at least a subset of ME/CFS patients. The finding needs replication.

hla t cell b.jpg

Does ice cream cause sunburn? The evidence for this is that many people who buy ice cream also get sunburn. Of course, ice cream doesn’t cause sunburn, people buy ice cream and get sunburn on sunny days. But this illustrates a problem faced by researchers: just because two things occur together is no guarantee that one causes the other.

Take the example of cytokines, immune messenger molecules, in ME/CFS. Researchers have found abnormalities in the level of several cytokines, which could be evidence that problems in the immune system are driving ME/CFS. Equally, the cytokine abnormalities could simply be the result of ME/CFS or just a general effect of being ill.

However, genetic studies provide a solution to this cause-or-effect problem. When genetic differences are linked to an illness, it is evidence that the gene differences play a causal role. The reason is that we are born with our genes and ME/CFS develops much later: since genetic differences come first they must play a role in causing the illness...

Read the full blog

Discussion thread on the paper
 
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Firstly, I would not be at all surprised to find the immune system is implicated. My wife (the pwME) also has immune related issues - hayfever, food issues, etc.

But something I'd like to better understand.

I notice you carefully use the phrase "play a causal role in ME/CFS", which presumably includes a cause that might itself be quite a long way removed from the immune system itself. Is it possible that the immune system differences might simply be causing changes in some other part of a person's biology, and it could then be that which causes the problem instead, not the immune system?
 
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Simon M said:
The best evidence yet that immune system problems can cause ME/CFS?

Human leucocytes Antigen (HLA) proteins play an essential role in helping the immune system to recognise pathogens. This new research is easily the best study yet of HLA alleles (gene variants) in ME/CFS. It finds links between at alleles of least two HLA genes and ME/CFS. And since the illness can’t change (HLA) DNA, the link must be that the alleles must play a causal role in ME/CFS. So this evidence that the immune system plays a causal role for at least a subset of ME/CFS patients. The finding needs replication.
Click to expand...
Just a typo:

"It finds links between at alleles" (3rd sentence)
 
Barry said:
I notice you carefully use the phrase "play a causal role in ME/CFS", which presumably includes a cause that might itself be quite a long way removed from the immune system itself. Is it possible that the immune system differences might simply be causing changes in some other part of a person's biology, and it could then be that which causes the problem instead, not the immune system?
Click to expand...
Good question. What I meant was that these alleles did not of themselves cause ME/CFS, not in the way that faulty genes cause cystic fibrosis, for instance. Instead, they contribute to getting ME/CFS so what the study really measures is an increased risk of getting the illness (about 50%-100% higher, but remember the risk is pretty low in the first place).

Two possible ways these HLA alleles might increase risk are by increasing the chance of a severe infection or increasing the chance of autoimmunity. HLA alleles are known to affect the chances of getting specific infections or particular autoimmune diseases. (One HLA allele both protects against HIV progressing to AIDS and also increases the chance of getting autoimmune diseases.)

But, assuming the finding holds up, the alleles are playing a causal role of some sort. Finding it might not be so easy.
 
Jimmy86 said:
  • C allele: patients, 7.7%; controls, 3.8% of controls
  • D allele: patients, 12.7%, controls, 8.7%
What are the standard deviations and are these differences statistically significant?
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I tend not to quote stats in my blogs, but I only blog about results that are statistically significant. Here are the stats:
HLA-C*07:04 (OR 2.1 [95% CI 1.4–3.1])
HLA-DQB1*03:03 (OR 1.5 [95% CI 1.1–2.0])

OR is odds ratio (chance of having it as a patient relative to controls). The confidence intervals don't include 1.0 so the results are statistically significant, and have been corrected for multiple comparisons. Odds ratios (used for binary data) come from logistic regression so don't use standard deviation directly.

@Barry @ScottTriGuy thanks for the shares
 
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