A multiplex serologic platform for diagnosis of tick-borne diseases, 2018, Tokarz, Lipkin et al

Andy

Retired committee member
Abstract
Tick-borne diseases are the most common vector-borne diseases in the United States, with serology being the primary method of diagnosis. We developed the first multiplex, array-based assay for serodiagnosis of tick-borne diseases called the TBD-Serochip. The TBD-Serochip was designed to discriminate antibody responses to 8 major tick-borne pathogens present in the United States, including Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, Ehrlichia chaffeensis, Rickettsia rickettsii, Heartland virus and Powassan virus.

Each assay contains approximately 170,000 12-mer linear peptides that tile along the protein sequence of the major antigens from each agent with 11 amino acid overlap. This permits accurate identification of a wide range of specific immunodominant IgG and IgM epitopes that can then be used to enhance diagnostic accuracy and integrate differential diagnosis into a single assay.

To test the performance of the TBD-Serochip, we examined sera from patients with confirmed Lyme disease, babesiosis, anaplasmosis, and Powassan virus disease. We identified a wide range of specific discriminatory epitopes that facilitated accurate diagnosis of each disease. We also identified previously undiagnosed infections. Our results indicate that the TBD-Serochip is a promising tool for a differential diagnosis not available with currently employed serologic assays for TBDs.
Open access at https://www.nature.com/articles/s41598-018-21349-2

Article on this study
A new blood test called the Tick-Borne Disease Serochip (TBD Serochip) promises to revolutionize the diagnosis of tick-borne disease by offering a single test to identify and distinguish between Borrelia burgdorferi, the pathogen responsible for Lyme disease, and seven other tick-borne pathogens. Led by scientists at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health, the research team reports details on the new test in the journal Nature Scientific Reports.

The researchers—who also include scientists from the Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, Roche Sequencing Solutions, Farmingdale State College, and Stony Brook University—sought to improve on existing tests for tick-borne diseases (TBDs), which have limited diagnostic accuracy and cannot test for more than one infection simultaneously. Currently, diagnosis of Lyme disease, the most common TBD, requires two separate tests. This cumbersome approach also relies on subjective criteria for the interpretation of results, and accurately identifies fewer than 40 percent of patients with early disease and results in false positives 28 percent of the time. The accuracy of the method used to diagnose TBDs Babesia, Anaplasma, Ehrlichia, and Rickettsia varies widely among testing laboratories. And for other tick-borne agents, specific blood tests are not yet available, or in the case of the potentially deadly Powassan virus or Heartland virus, are only performed in specialized laboratories.

“The number of Americans diagnosed with tick-borne disease is steadily increasing as tick populations have expanded geographically,” says Rafal Tokarz, PhD. “Each year, approximately 3 million clinical specimens are tested for TBDs in the U.S. Nonetheless, the true incidence of TBDs is likely greatly underestimated, as patients with presumed TBDs are rarely tested for the full range of tick-borne agents, and only a fraction of positive cases are properly reported,” adds Nischay Mishra, PhD. Co-lead authors Tokarz and Mishra are associate research scientists in the Center for Infection and Immunity.
https://www.mailman.columbia.edu/public-health-now/news/first-multiplex-test-tick-borne-diseases

Edit: Change title of thread to title of paper, add paper abstract and link.
 
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Eh.

Although it would be good to have a packaged lab approach to helping diagnose multiple TBDs, I am under the impression after reviewing this that it would still only be testing for exposure, which for Lyme at least means we cannot distinguish an active infection. If I am misinterpreting this, please let me know. Regardless, we desperately need better direct testing techniques (which this doesn't appear to be), which applies to Babesia as well.

I also noticed this doesn't seem to include Bartonella.

Convenience counts, though, so I suspect it may serve a very real purpose for the average clinician. They will still have to buck the stranglehold the 2T and C6 have on today's Lyme market.
 
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Edited original post to change title of thread to title of paper, add paper abstract and link.
 

think it would be a hit if you or another person who knows about lyme science and politics decided to write:

"a primer for pwme about lyme and tbd"

not that i'm asking you or anybody to perform the work, but learning a bit about the epidemiology [with chronology/geography/species], pathogens, symptom profiles, /current/ testing, /current/ politics etc. by a really knowledgeable person i think would have broad appeal in the m.e. community.

[not limited to lyme; this type of primer would also be great with all sorts of differential diagnoses and political analogues, like gulf war, eds, b12, sle, heavy metal poisoning, etc.]
 
Lipkin was joined in this effort with Lyme royalty: Adrianna Marques of the NIH, and Brian Fallon of Columbia U's Tick team. That's significant backing.

I wonder if a clinician ordering the test for a patient can pick and choose those pathogens he wants tested, or if it's a set template, and ALL listed pathogins are tested for each and everytime.

There are endemic areas where odds are heavy that if a tick bites you, you just wont pick up Lyme...You pick up one or two or three other infections. A test like this could in a single swoop take the guess work out of which tbds you'd been exposed to, bartonella notwithstanding.

I love that miyamotoi is included, but that smart add imo is offset by not have bartonella, which is arguably the second most prevalent disease next to Lyme - and every bit as difficult to treat.
 
Open access at https://www.nature.com/articles/s41598-018-21349-2

Article on this study

https://www.mailman.columbia.edu/public-health-now/news/first-multiplex-test-tick-borne-diseases

Edit: Change title of thread to title of paper, add paper abstract and link.

*Extract from a recent article by Cort Johnson [http://simmaronresearch.com/2020/01/lipkin-serochip-chronic-fatigue-syndrome/]. Perhaps @Jonathan Edwards could give us his view of the technology Lipkin is using.

*Simmaron Research (1st January 2020):
"The Serochip will scan through up to 6 million peptides (small amino acid chains) in an attempt to uncover a hidden pathogen that has been, or still is, tweaking ME/CFS patients’ immune systems. The work could also uncover an autoimmune reaction.

ME/CFS with its multiple subsets is likely far more complex than AFM, but if Lipkin can find a distinct immune signature or more likely distinct immune signatures in ME/CFS, he might be able to break another mysterious, pathogen triggered disease wide open.

Lipkin and his team will begin testing the blood or spinal fluid of ME/CFS patients in early 2020."

Open access at https://www.nature.com/articles/s41598-018-21349-2

Article on this study

https://www.mailman.columbia.edu/public-health-now/news/first-multiplex-test-tick-borne-diseases

Edit: Change title of thread to title of paper, add paper abstract and link.

@Jonathan Edwards what do you think about this technology?

http://simmaronresearch.com/2020/01/lipkin-serochip-chronic-fatigue-syndrome/

"The Serochip will scan through up to 6 million peptides (small amino acid chains) in an attempt to uncover a hidden pathogen that has been, or still is, tweaking ME/CFS patients’ immune systems. The work could also uncover an autoimmune reaction.

ME/CFS with its multiple subsets is likely far more complex than AFM, but if Lipkin can find a distinct immune signature or more likely distinct immune signatures in ME/CFS, he might be able to break another mysterious, pathogen triggered disease wide open.

Lipkin and his team will begin testing the blood or spinal fluid of ME/CFS patients in early 2020."
 
@Jonathan Edwards what do you think about this technology?

http://simmaronresearch.com/2020/01/lipkin-serochip-chronic-fatigue-syndrome/

"The Serochip will scan through up to 6 million peptides (small amino acid chains) in an attempt to uncover a hidden pathogen that has been, or still is, tweaking ME/CFS patients’ immune systems. The work could also uncover an autoimmune reaction.

It looks like a waste of time to me, sadly. This sort of mass peptide screening technology seems unlikely to find anything. I suspect they are still stuck in the idea of molecular mimicry, which has got us nowhere and makes no sense.

What seems tome pity is that there are groups like this with good scientific technical skills but little understanding of how immunological disease works in practice chasing things that we have no real reason to think will ever be found.
 
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It looks like a waste of time to me, sadly. This sort of mass peptide screening technology seems unlikely to find anything. I suspect they are still stuck in the idea of molecular mimicry, which has got us nowhere and makes no sense.

What seems tome pity is that there are groups like this with good scientific technical skills but little understanding of how immunological disease works in practice chasing things that we have no real reason tithing will ever be found.
Interesting thank you for your response.
 
It looks like a waste of time to me, sadly. This sort of mass peptide screening technology seems unlikely to find anything. I suspect they are still stuck in the idea of molecular mimicry, which has got us nowhere and makes no sense.

What seems tome pity is that there are groups like this with good scientific technical skills but little understanding of how immunological disease works in practice chasing things that we have no real reason to think will ever be found.

Thanks @Jonathan Edwards.
Here's an extract from Cort's article:
"The peptide arrays proved the trick. Lipkin found antibodies to EV peptides present in almost 80% of the study participants’ CSF, and zeroed in on a specific enterovirus called EV-D68. Since then a separate study has confirmed his finding. Now some researchers are calling acute flaccid myelitis “the new polio“."

So, they seemed to get a reasonably consistent result from the peptide array (80% of cerebro spinal fluid samples). So perhaps peptide arrays can identify the presence of antibodies and then you need to identify the target of these antibodies - in this case a virus. I'd prefer to see a published paper, anyone aware of a paper based on Lipkin's work on acute flaccid myelitis - or other relevant paper?
 
So, they seemed to get a reasonably consistent result from the peptide array (80% of cerebro spinal fluid samples).

It is very hard to know if there is anything 'consistent' here. Peptide arrays will always appear to give a result. The question is whether it means anything. Cort's reporting of science tends to be uncritical and hyped as you probably know.
 
It is very hard to know if there is anything 'consistent' here. Peptide arrays will always appear to give a result. The question is whether it means anything. Cort's reporting of science tends to be uncritical and hyped as you probably know.
Thank you for your reply.
 
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