Pathogenesis of Post-Lyme Disease Symptoms

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
hv808ct
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Pathogenesis of Post-Lyme Disease Symptoms

Post by hv808ct » Sun 11 May 2014 14:57

Pathogenesis of Post-Lyme Disease Symptoms.
Seligman SJ, Petzke MM, Bogunovic D.
Clin Infect Dis. 2014 May 7.


In an effort to understand the pathogenesis of post-Lyme disease symptoms, the article by Strle et al estimated the levels of 15 cytokines and an additional 11 chemokines in erythema migrans patients from Slovenia [http://cid.oxfordjournals.org/content/58/3/372.abstract]. Their finding of elevated levels of the type 17 helper T-cell (TH17)-associated interleukin 23 (IL-23) in some of the patients with persistent symptoms is a valuable addition to attempts to understand the pathogenesis of the perplexing phenomena of post-Lyme disease symptoms following the apparently successful antibiotic treatment of Borrelia burgdorferi sensu lato (B. afzelii and B. garinii).

The few markedly elevated levels of the type 1 helper T cell chemokines CXCL9 and CXCL10 prior to receiving antibiotics were associated with the absence of symptoms on subsequent visits. No other abnormalities in cytokines or chemokines were found. As noted in the Strle article, other instances of the stimulation of innate and adaptive immune response following Borrelia infection have been reported.

More recently, Jacek et al [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557545/] studied patients with post-Lyme disease symptoms following treatment of the B. burgdorferi sensu stricto present in the United States. They found that persistent symptoms were associated with activation of specific target genes of the innate immune system, suggesting increased IFN-alpha activity. However, the observations of Strle et al of normal levels of cytokines other than IL-23 considerably restrict the variety of cytokines likely to be involved with post-Lyme disease symptoms.

Still a complete understanding the pathogenesis of post-Lyme disease symptoms remains an elusive goal.

Strle et al found that 18/510 (3.5%) of their patients had symptoms that were present at 12 months. Perhaps unfortunately the severity and type of these symptoms are not discussed. As can be calculated from data in the article, six of the patients with persistent symptoms never had elevated IL-23 levels.

[snip]

Lastly the prevalence of persistent symptoms for one year in 3.5% of Lyme disease patients is similar to that to be expected in the general population and is thereby consistent with the hypothesis that, in some cases, the symptoms are unrelated to Borrelia infection.

duncan
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by duncan » Sun 11 May 2014 16:54

Well, I have to say it's nice to see someone is looking for biomarkers.

Still, as indicated in the title of the study, if you enter any endeavor with an implanted bias, is it a stretch to wonder if the results might carry a bias?

Of course, I was struck by one part of a sentence in the first paragraph that sums up a good deal of my difficulty with this study: "perplexing phenomena of post-Lyme disease symptoms following the apparently successful antibiotic treatment of Borrelia..."

If you posit that the "post" in post-Lyme is inappropriate, that it is still active Lyme, then the "perplexing" factor gets eliminated, and the"apparently successful antibiotic treatment" is not so apparently successful after all.

Come to think of it, perhaps the whole success or failure of the study hinges on the word "apparently."

I get that looking at cytokines and chemokines may be a good thing moving forward, but I've seen these efforts before - e.g. many in the ME/CFS realm, or even CXCL13 in Lyme - and they seldom if ever seem to generate enough interest to be replicated, or gain enough traction to be embraced by mainstream medicine.

velvetmagnetta
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by velvetmagnetta » Sun 11 May 2014 17:45

It is a relief to see that somebody is looking at what happens after a rigorous antibiotic treatment. Something is very wrong with many of us whose infections are most likely dead, and yet our symptoms are still many and painful and debilitating.

If some of us actually did successfully treat the Lyme infection and are still suffering, then, what is going on?

I know many on Lymenet believe that the infection is still alive and active, but what if it's not? What then could possibly be ailing us?

duncan
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by duncan » Sun 11 May 2014 19:06

I will take a stab at that, velvetmagnetta, if that's ok. There are many people on the forum who are far more knowledgeable than I, though, and hopefully they can elaborate on - or correct - what I write.

Broadly speaking, there are two alternatives to continued symptoms vs continued infection:

First, our immune systems got activated by Bb, and even though Borrelia was cleared from our bodies, elements of our immune system got locked in activated mode, and do not deactivate. More or less, we develop an auto-immune response that is relentlessly attacking the host, despite no infection being present. I apologize for the simplistic overview.

Second, damage from the Bb infection was severe enough to leave some symptoms with the patient forever, or for a long time.

Of course, it could be a combination of the two.

Edited to add: You know, there is a third possibility, namely that Bb stirred up a latent infection or pathogen, viral or retroviral in nature. Not a lot of research has been directed this way, though. Oh, and naturally, continued symptoms could be from other tbd's. Wish I could remember all this stuff in one pass, instead of bits and pieces. :)

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LHCTom
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by LHCTom » Sun 11 May 2014 23:52

There seems to be an assumption with chronic Lyme or PTLDS that the symptoms are caused by some kind of immune system dysregulation. This in turn leads to the obvious search for immune system inflamatory or signaling markers such as chemokines or cytokines that appear abnormal. This of course is a sensible place to look but its only the tip of a very large iceburg.

Another far broader approach is using the latest metabolomics tools such as GC-MS ( gas chromatography and mass spectrometer) to explore metabolite signatures in people with Chronic Lyme or PTLDS. Metabolomics is the study of chemical processes involving metabolites. It refers to the set of small-molecule metabolites found in the patients blood, urine or other biological samples.

In a study I'm following on ME/CFS, metabolomics using a GC-MS identifies and measures about 870 small molecules under about 2000kDa in your blood. It then looks for patterns or a signature that is common to ME/CFS or any chronic illness that is impacting the metabolic system in your body. The signature is a very useful biomarker but even more important, they will attempt to trace the source of the anomolies back upstream in about 60+ metabolic pathways. If anomolies are found and are able to be traced to a metabolic path problem, it opens the door to both understanding what is wrong and may even suggest what needs to be done to correct the problem.

UCSD has an NIH funded metabolomics program described here:

http://www.jacobsschool.ucsd.edu/news/n ... fe?id=1265

One of there efforts on a chronic disease uncovered a Signature of Mitochondrial Dysfunction in Diabetic Kidney Disease:

http://jasn.asnjournals.org/content/ear ... 068a21abe8

You can see more here:

http://www.ucsdbglab.org/metabolomics/Visualization.asp

The UCSD Division of Medical genetics is using the Metabolomics tools at UCSD to investigate chronic illnesses or conditions including Autism, PTSD, Brain Injury and now may begin on ME/CFS including Dr Naviaux's Lab

http://medgenetics.ucsd.edu/research/Pa ... x-lab.aspx

Whether you believe, Chronic Lyme is an ongoing infection or is a result of some kind of dysregulation in the body, studying metabolites through metabolomics "looks" for specific problems in the metabolic system metabolites and has an excellent chance of catching the results of the "problem". Not only does it "look" at the many pathways but our microbiota are involved in a portion of the metabolic pathways and are necessary. So even gut microbiome problems could play a role and might get caught in the Metabolomics signature as well.

Many of us experience Chronic Lyme or PTLDS with symptoms very similar to those with ME/CFS. Many of us have been diagnosed with both. Columbia's Ian Lipkin and others completed a search for pathogens common in ME/CFS recently and came up blank. But along the way, Lipkin has been curious if the gut microbiome might play a role. So he is pursuing a ME/CFS microbiome study.

http://phoenixrising.me/archives/21929

That is what has led to ME/CFS studies with fecal transplants and some success. But one of the more important roles of our microbiome is its role as part of our metabolism. Those microbes in our guts are an integral part of human metabolism. There is no end to the number of problems a broken metabolism can cause. So this metabolomics approach to ME/CFS might turn out to be one possible approach to finding the cause of chronic Lyme PTLDS symptoms. Stay tuned.
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

RitaA
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by RitaA » Mon 12 May 2014 1:24

There's more about metabolomics here:

http://www.lymeneteurope.org/forum/view ... =13&t=1419

velvetmagnetta
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by velvetmagnetta » Mon 12 May 2014 7:39

LHCTom:

Would metabolites be able to tell us anything if the problem lies in the nervous system?

Duncan:

Cytokines and other immune system products of inflammation are not enough to explain all the problems of post-treatment patients. Our problems extend far beyond the pain of inflammation - especially all the strange neurological symptoms like spasms, confusion, and severe pain.

Perhaps when the spine becomes inflamed it causes all these problems? But if that were so, then we would have probably seen these problems in meningitis and encephalitis patients.

Margherita
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by Margherita » Mon 12 May 2014 14:53

Duncan wrote:
Broadly speaking, there are two alternatives to continued symptoms vs continued infection:

First, our immune systems got activated by Bb, and even though Borrelia was cleared from our bodies, elements of our immune system got locked in activated mode, and do not deactivate. More or less, we develop an auto-immune response that is relentlessly attacking the host, despite no infection being present. I apologize for the simplistic overview.

Second, damage from the Bb infection was severe enough to leave some symptoms with the patient forever, or for a long time.

Of course, it could be a combination of the two.

Edited to add: You know, there is a third possibility, namely that Bb stirred up a latent infection or pathogen, viral or retroviral in nature. Not a lot of research has been directed this way, though. Oh, and naturally, continued symptoms could be from other tbd's. Wish I could remember all this stuff in one pass, instead of bits and pieces. :)
Duncan, laypersons like me are very grateful for your simplistic overview :) .

My Lyme disease was diagnosed only 18 years after my first Lyme symptoms started. A year of antibiotics wasn't sufficient to solve the problem and my doctor isn’t willing any longer to prescribe more antibiotics. In this stage especially the inflammatory symptoms are increasing and getting worse. Not only my joints are involved but also my skin and the worst of all is my gut which results in a considerable weight loss and several food intolerances.

I learned that anti inflammatory medicines are not recommended for Lyme patients. But let’s suppose that I’m dealing with an auto immune reponse attacking me without an infection being present; then why not give it a try? Are there any late/chronic Lymepatients on this forum who did and tried anti inflammatory drugs? In case there are, what were their experiences?

(As I told before on this forum, one of my family members suffers Wegener disease. He’s been prescribed both; antibiotics(!) and anti inflammatory drugs for the rest of his life. And he’s feeling far better than I do).

duncan
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by duncan » Mon 12 May 2014 16:11

Yep, it's a tough position to be in. There are some doctors that believe you can treat both simultaneously. It has been suggested by one of my physicians to me that I go on immune modulators for my immune system, AND antibiotics for Borrelia. Problem for me is that I don't know if I want anybody tweaking my immune system - still kinda experimental - if I am carrying an active infection. IF someone believes the infection has been cleared, then "managing" the immune system is an option. I think that one proposed treatment that is going to trial in Texas is based on manipulating the immune system. Tom might know that, or Rita, or anyone of the other members who are so much better at the science involved than I.

Perhaps partially because of my ignorance, I just don't trust the science yet, and I don't believe the mainstream researchers have proven their case yet that they can conclusively claim Borrelia has been eradicated in me. So I stick to abx. I err in that direction. I don't know if I am right, though. That's a personal choice.

Margherita
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by Margherita » Mon 12 May 2014 17:14

Thanks Duncan. I understand your point of view. Honestly I wonder to what degree a year of oral antibiotics might have completely eradicated my Borrelia infection. Furthermore I'm dealing with some co-infections and persisting viruses as well. So at that point I'ld be willing to try both, antibiotics and anti inflammatory drugs. The problem is ... my doctor isn't willing :roll:

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