Lyme Disease: Gene Signatures May Catch the Infection Sooner

Remy

Administrator


Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease
  1. Jerome Bouqueta,
  2. Mark J. Soloskib,
  3. Andrea Sweic,
  4. Chris Cheadleb,
  5. Scot Federmana,
  6. Jean-Noel Billaudd,
  7. Alison W. Rebmanb,
  8. Beniwende Kabrea,
  9. Richard Halpertd,
  10. Meher Boorgulab,
  11. John N. Aucottb,
  12. Charles Y. Chiua
ABSTRACT
Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months.

The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment.

The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets.


http://mbio.asm.org/content/7/1/e00100-16
 

Remy

Administrator
Dr Francis Collins expands on the findings of this Lyme disease research in his blog post found here:

An NIH-supported team recently uncovered a unique gene expression pattern in white blood cells from people infected with the Lyme disease-causing bacterium Borrelia burgdorferi [1]. This distinctive early gene signature, which persists after antibiotic treatment, is unique from other viral and bacterial illnesses studies by the team. With further work and validation, the test could one day possibly provide a valuable new tool to help doctors diagnose Lyme disease earlier and help more people get the timely treatment that they need.

The new study, published in the online journal mBio, was led by researchers Charles Chiu of the University of California, San Francisco, and John Aucott of Johns Hopkins University, Baltimore. The Hopkins group enrolled 29 adults from Maryland with newly diagnosed Lyme disease and 13 healthy adult controls. For the Lyme patients, blood samples were taken at three time points: 1) immediately upon their diagnosis, 2) just after they’d completed a standard, 3-week course with antibiotic doxycycline taken orally, and 3) 6 months after treatment.

By the end of the study, about half of the patients had made a full recovery. The others continued to contend with lingering fatigue, joint pain, cognitive dysfunction, and other symptoms. Four people later were diagnosed with post-treatment Lyme disease syndrome (PTLDS) based on a documented functional decline over time. It’s estimated that, for still unknown reasons, 10 to 20 percent of people with Lyme disease progress to PTLDS. That doesn’t appear to represent ongoing infection, but some disruption of the immune system that persists after the pathogen has been eliminated.

Hoping to get a better handle on these varied treatment outcomes, the researchers turned their attention to various types of immune cells in the patient blood samples. Because the immune system typically responds differently to different infections, the researchers wondered whether these white blood cells produce a distinctive gene signature when mounting a response to B. burgdorferi. To get the answer, they compared the transcriptomes—the RNA gene transcripts expressed by a cell’s genome at a given time—of people with Lyme disease to those from the healthy controls.

Their analyses uncovered changes in the expression of more than 1,000 genes at the time of diagnosis. Many of the changes reflect inflammatory and immune responses, as expected in a person battling an infection. Further analyses showed that just under half of the observed differences in gene expression were shared with other common illnesses, making Lyme disease a relatively unique infection. Interestingly, the gene expression signature in early Lyme disease had more in common with viral influenza infections than infections caused by other bacteria.

For the vast majority of infectious diseases, effective treatment allows the immune system to stop fighting and return gene expression levels to normal. Remarkably, that was not the case with Lyme disease. The immune cells had post-treatment transcriptomes that varied from those of healthy controls by about 1,000 genes. This signature also included many of the underlying inflammatory and immune features seen in the pre-treatment response, and even as patients began to feel better.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Dr Francis Collins expands on the findings of this Lyme disease research in his blog post found here:
This is great! I love post-infectious stuff.... I wonder if they can use the Lyme cohort they're including in the NIH study to look at this as well....I hope they're doing an transcriptome analysis - whatever that is. Given Collins interest in this maybe they are.

Thanks! I'm going to do a blog on this :)
 
Last edited:

Judi

Member
I have not been tested for Lyme disease but people (from forum groups on other web sites) insist that is exactly what I should do. In the mid 80's I was diagnosed with RA and a few years after that I was diagnosed with fibromyalgia. My current rheumatologist says I have CFS but there has never been any mention of testing for Lyme. As far as I know I've never had a tick bite, headaches, fever or chills so I ruled out Lyme, especially with the false-positive test results I have never been motivated to do so. It seems to me after seeing RA doctors for the past 30 years Lyme would have been questioned? And if I do have Lyme most likely it is post-infectious now and available for treatment doesn't sound promising.
Cort I look forward to your blog on this subject.
 

Remy

Administrator
I have not been tested for Lyme disease but people (from forum groups on other web sites) insist that is exactly what I should do. In the mid 80's I was diagnosed with RA and a few years after that I was diagnosed with fibromyalgia. My current rheumatologist says I have CFS but there has never been any mention of testing for Lyme. As far as I know I've never had a tick bite, headaches, fever or chills so I ruled out Lyme, especially with the false-positive test results I have never been motivated to do so. It seems to me after seeing RA doctors for the past 30 years Lyme would have been questioned? And if I do have Lyme most likely it is post-infectious now and available for treatment doesn't sound promising.
Cort I look forward to your blog on this subject.
Hi Judi!

As you probably already know, nothing about Lyme is straight forward or simple, unfortunately. Lyme testing is particularly challenging but I would have to agree that testing for Lyme with a reputable company like IgeneX is probably something that should be considered. You can get their plain Western blots (IgM and IgG) for under $200 and I think it is a worthwhile investment. Especially since you've got a few conditions that are often considered to have an infectious basis.

I wouldn't count on any traditional medicine doctor to recognize chronic Lyme or to suggest testing for it. It would be weird if they did, honestly! And a good number of people don't ever remember a bite from a tick. The deer tick that transmits Lyme is tiny, tiny, tiny. Some people never get the bullseye rash at all. And mosquitoes may be able to transmit it. There's just so much about Lyme that we don't yet know, unfortunately.

FWIW, it's more likely to get a false negative (meaning you have Lyme but the test is negative) than a false positive with the current tests.

I have a friend with RA and she has had good luck with boron...might be something to look into.

Good luck!
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
The FDA s currently evaluating the efficacy of different Lyme tests. I imagine at the end of it all some tests may be removed from the market.
 

Remy

Administrator
The FDA s currently evaluating the efficacy of different Lyme tests. I imagine at the end of it all some tests may be removed from the market.
Honestly, the only test that I would really ever do is the Western blot and that testing methodology won't ever be removed from the marketplace because it is used to diagnose other illnesses as well.

The Lymphocyte Tolerance Test also looks to have some validity. I think that is the methodology used by KDM...EliSpot.
http://www.bca-lab.de/

I did a version of this through Neuroscience a few years ago...it showed my immune system was in overdrive which should have been my first clue that immune deficiency was not necessarily my problem!
 

Judi

Member
The FDA s currently evaluating the efficacy of different Lyme tests. I imagine at the end of it all some tests may be removed from the market.
Dr Armin Schwarzbach was at the LDN conference last month to introduce his laboratory ArminLab in Germany. http://www.arminlabs.com/ The lab test for Borrelia burgdorferi Elispot:
Borrelia b. fully antigen + Borrelia b. peptide mix + LFA-1. This is the test I'm going to use to determine Lyme disease. I wonder if this is the test that will replace some of the test on the market?
 

Remy

Administrator
Dr Armin Schwarzbach was at the LDN conference last month to introduce his laboratory ArminLab in Germany. http://www.arminlabs.com/ The lab test for Borrelia burgdorferi Elispot:
Borrelia b. fully antigen + Borrelia b. peptide mix + LFA-1. This is the test I'm going to use to determine Lyme disease. I wonder if this is the test that will replace some of the test on the market?
Armin was associated with Infectolabs (the link I posted for the EliSpot) above and they broke apart and he started Armin Labs.

I'm not certain how the test is or isn't different from the Infectolab EliSpot but I'd say they are similar.

This testing method does look promising but the reason I recommend people get the IgeneX Western blots is because they are typically covered by insurance (even Medicare!) and the EliSpot testing is usually harder to get covered. They both have pros and cons in terms of usefulness otherwise.
 

Judi

Member
Armin was associated with Infectolabs (the link I posted for the EliSpot) above and they broke apart and he started Armin Labs.

I'm not certain how the test is or isn't different from the Infectolab EliSpot but I'd say they are similar.

This testing method does look promising but the reason I recommend people get the IgeneX Western blots is because they are typically covered by insurance (even Medicare!) and the EliSpot testing is usually harder to get covered. They both have pros and cons in terms of usefulness otherwise.
Thank you Remy I have RA, fibromyalgia and CFS but I keep hearing about how I need to get tested for Lyme so maybe I will. I don't think I have Lyme, I don't have a lot of the symptoms and the symptoms I do have are uncommon for Lyme. Still haven't decided for sure if I'll do the test I'll think it over for a few days.
I'm researching and reading the articles Cort has written on Lyme I trust his site :).
 

Judi

Member
Honestly, the only test that I would really ever do is the Western blot and that testing methodology won't ever be removed from the marketplace because it is used to diagnose other illnesses as well.

The Lymphocyte Tolerance Test also looks to have some validity. I think that is the methodology used by KDM...EliSpot.
http://www.bca-lab.de/

I did a version of this through Neuroscience a few years ago...it showed my immune system was in overdrive which should have been my first clue that immune deficiency was not necessarily my problem!
Is IgeneX the only lab to use for the western blot test?
 

Remy

Administrator
Is IgeneX the only lab to use for the western blot test?
It is the only lab I would use because they test for more strains of the bacterial and use a better test medium than others (like Labcorp).

They will also report positive, negative or indeterminate bands. Many LLMDs regard any activity on a band as evidence of infection but a Labcorp Western blot might just report that as a negative. So you get more sensitivity as well.
 

Judi

Member
It is the only lab I would use because they test for more strains of the bacterial and use a better test medium than others (like Labcorp).

They will also report positive, negative or indeterminate bands. Many LLMDs regard any activity on a band as evidence of infection but a Labcorp Western blot might just report that as a negative. So you get more sensitivity as well.
Thank you Remy. So I went to my GP today he ordered Lyme test the lab is Soltace now owned by Quest Diagnostics. He would not sign off on an order to send to IgeneX. I had the blood drawn and they will have results in 8 - 10 days. He told me I should see psychiatrist for anti depressants since that is why I have CFS (eye roll). Now I need to find a doc who will sign off on a blood draw and use IgeneX.
 

Judi

Member
It is the only lab I would use because they test for more strains of the bacterial and use a better test medium than others (like Labcorp).

They will also report positive, negative or indeterminate bands. Many LLMDs regard any activity on a band as evidence of infection but a Labcorp Western blot might just report that as a negative. So you get more sensitivity as well.
Thank you Remy. So I went to my GP today he ordered Lyme test the lab is Soltace now owned by Quest Diagnostics. He would not sign off on an order to send to IgeneX. I had the blood drawn and they will have results in 8 - 10 days. He told me I should see psychiatrist for anti depressants since that is why I have CFS (eye roll). Now I need to find a doc who will sign off on a blood draw and use IgeneX.
 

Remy

Administrator
Thank you Remy. So I went to my GP today he ordered Lyme test the lab is Soltace now owned by Quest Diagnostics. He would not sign off on an order to send to IgeneX. I had the blood drawn and they will have results in 8 - 10 days. He told me I should see psychiatrist for anti depressants since that is why I have CFS (eye roll). Now I need to find a doc who will sign off on a blood draw and use IgeneX.
Time to fire that :asshat:!!

Sometimes they will do the two tier testing at Labcorp and Quest...it's ELISA testing and only if that is positive will it do the Western blot. So if it says negative, basically just reserve judgment.
 

Get Our Free ME/CFS and FM Blog!



New Threads

Forum Tips

Support Our Work

DO IT MONTHLY

HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT

Shopping on Amazon.com For HR

Latest Resources

Top