Infection Elicited Autoimmunity and ME/CFS (2018) Blomberg et al

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

Jonas Blomberg 1, Carl-Gerhard Gottfries 2, Amal Elfaitouri 3, Muhammad Rizwan 1 and Anders Rosén 4

1. Department of Medical Sciences, Uppsala University, Clinical Microbiology, Academic Hospital, Uppsala, Sweden
2. Gottfries Clinic AB, Mölndal, Sweden
3. Department of Infectious Disease and Tropical Medicine, Faculty of Public Health, Benghazi University, Benghazi, Libya
4. Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden

Hypothesis and Theory ARTICLE
Front. Immunol., 15 February 2018 | https://doi.org/10.3389/fimmu.2018.00229

Abstract
Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging.

In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model.

ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism.

According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance.

Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension.

A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain.

In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones.

Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.

https://www.frontiersin.org/articles/10.3389/fimmu.2018.00229/full

 

The Swedish journal Socialmedicinsk Tidskrift published an article by Blomberg in 2016, on the same subject:

Infektionsutlöst autoimmunitet vid ME/CFS. En förklaringsmodell
http://socialmedicinsktidskrift.se/index.php/smt/article/view/1482/1257

 

Yes, that is one good explanation. A second might be that the infection persists, frequently at sub-clinical levels, at least in terms of most conventional labs.

 

I think the motivation for thinking autoreactivity is a major factor has diminished significantly since the negative rituximab trial. I do not personally think infection triggers autoimmunity, except perhaps in a very few exceptional instances. It needs some specific justification I think. Blomberg is a sensible careful investigator and he understands the complexities. I just do not share the enthusiasm for the mimicry idea.

 

And what about those people with ME who don't show autoimmunity (at least with the given technology)? Those wouldn't fit into this model, right?

 

They would fit if the autoimmunity is to an unknown antigen we have no test for.

 

Thanks. That's what I meant by "given the technology" - sometimes language makes it difficult.

 

I´m very happy to see that from today Jonas Blomberg is a member of the forum.

 

@Jonas Blomberg welcome.

 

A very warm welcome to S4ME @Jonas Blomberg, it's good to have you on board

 

Warmest welcome, @Jonas Blomberg, thank you for joining us!

 

Interesting that they mention dysbiosis in the Abstract.

There was no infection that elicited my condition, but I showed dysbiosis & substance intolerances on several tests.

 

what type of specific justification?

btw what do you think of pans/pandas? or fluoroquinolone autoreactivity?

 

The basic problem is that if molecular mimicry allowed autoimmunity to be triggered by infection then we should all have lethal autoimmune disease before we get to high school. There are billions of options for cross reactivity. Yet the proteins that become auto antigens are very few and very stereotyped. So we need a specific explanation for why mimicry should work for these. There are no specific explanations that I know of but there are perfectly good explanations of why we should get autoimmunity to these proteins without mimicry - because of the way the feedback loops in the immune system work.

Beofer I believe in molecular mimicry I would need someone to explain why it does not happen all the time. If you thin about it the theory is that self proteins are not recognised by the immune system, except sometimes they are. That is a pretty useless theory unless you can say WHY they are when they are . Molecular mimicry fails to do that.

From what I have read I thin PANDAS is probably a muddled idea that is not very helpful clinically. Immunological disease after streptococci is of course well known but in the original example of rheumatic fever I do not think anyone has ever substantiated the molecular mimicry idea. Streptococci probably subvert complement responses.


I was not aware that auto reactivity had been invoked in fluoroquinolone toxicity. I strongly suspect that is nonsense.

 

would complement be a possible link in creating autoantibodies?

e.g. in the transfer of repetitive behavior by igg transfusion in mice [possibly as an ocd or tourette's model -- did not read paper]?

i suspect the hornig and lipkin in the author list are mady and ian respectively.

https://www.ncbi.nlm.nih.gov/pubmed/19668249

>Furthermore, we demonstrate for the first time that humoral immunity is necessary and sufficient to induce the syndrome through experiments wherein naive mice are transfused with immunoglobulin G (IgG) from PANDAS mice.

 

The situation in mice is completely different. You can induce autoreactivity in rodents using powerful adjuvants if you breed animals that are susceptible. Even so most of the diseases created are monophonic with damage at the beginning. You can engineer just about any strange immunology in a mouse. That does not mean that anything similar occurs in humans.

 

Linköping Universitet: Nya rön kring kroniskt trötthetssyndrom
https://liu.se/nyhet/nya-ron-kring-kroniskt-trotthetssyndrom

Google Translate, English ("Linköping University: New Findings about Chronic Fatigue Syndrome")
https://translate.google.se/transla...on-kring-kroniskt-trotthetssyndrom&edit-text=

Well worth a read!