Tick Bite Sepsis: From Pseudoscience to Evidence-Based Research

By Kelly Irene and RJ James

Even tho there is plenty of science that demonstrates what Lyme Disease and its Outer Surface Proteins (Osps) do inside the human host, there are many evil people trying to keep Lyme and its crimes covered up. For decades, the debate about persistence vs non persistent has completely negated the opportunity for evidence-based activists to help bring justice to ALL Lyme patients (not just those who respond to treatments).
Evidence based activists face two key issues while trying to expose the truth about why Lyme Disease is such a “controversy”. Firstly, there is an abundance of advocates who either profit or at least benefit from the false persistence vs non-persistence dichotomy.
Secondly, the CDC/IDSA/ALDF continue to assert that evidence based activists are merely pseudoscientists who have no idea what they are talking about. In brief, “pseudoscience consists of statements, beliefs, or practices that are claimed to be both scientific and factual, but are incompatible with the scientific method” (Pseudoscience, 2018).  Sadly, that is what most Lyme Disease  activism currently is centered around: pseudoscience.
To avoid any claims that the literature provided in this blog is based of pseudoscience, there will be an abundance of literature from “credible scientists”. The studies used in this blog will be based off of systematic observation, measurement, experiment, formulation, testing, and modification of hypotheses.
Another thing to keep in mind is that the disease mechanisms provided in this blog are also shared by other abused groups such as Fibromyalgia (FM),  Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), Gulf War Illness (GWI), Autism, etc. (That will be explained in another blog). All that said, the key purpose of this blog is to help show Lyme activists that OspA, Pam3cys, and Post Sepsis Syndrome (PSS) are more than just buzz words in the Lyme community.
In order to properly understand what Lyme Disease does to the body, it is essential for Lyme activists to know that OspA is a key mechanism when it comes to understanding how the disease survive in it’s host. Borellia species undergo constant antigenic variation, whereby they shed Osps (i.e OspA) as a means of evading the immune system.  Because of these Osps, Lyme like diseases are not curable.
Spirochetes are pathologically parasitic, and are a relapsing fever organism. To put it differently, spirochetes are constantly pinching off their Osps to evade the immune response through a mechanism that Alan Barbour calls ‘blebbing’ (Barbour, Todd & Stoenner, 1982). These shed blebs are salso covered in lipoproteins known variable major proteins (Vmps).

(Barbour, Todd & Stoenner, 1982).

Since much of the science on Lyme Disease is based off of research fraud committed by Steere et al in 1994, any research used to expose the truth has be based off studies that show it’s true disease mechanisms in parallel with similar types of organisms. When it comes to Lyme Disease (OspA),  it is very similar in structure to Pam3cys.
Pam3cys is a “TLR1/TLR2 agonist” (Pam3Cys, 2018). More specifically, it is a synthetic analog of the triacylated N-terminal part of bacterial lipoproteins” (Pam3Cys, 2018). Simply put, Pam3cys is a molecule that stops the immunity chain reaction in the immune systems Toll Like Receptors.

Toll Like Receptors: TLR2 manages mycobacteria or fungal endotoxins
Toll-like receptors are immune receptors that participate in the first line of defense against invading pathogens. They play a critical role in the innate immune response by recognizing the distinct molecular structure of invading pathogens.
Below is some evidence based literature that explains TLR 2’s mechanisms:
“The innate immune system utilizes multiple receptors to recognize fungal pathogens, and the net inflammatory response is controlled by interactions between these receptors. Many fungi are recognized, at least in part, by Toll-like receptor 2 (TLR2).”(Goodridge & Underhill, 2008).
“The agonists include bacterial lipoproteins (44, 53, 54), Gram-positive bacterial lipoteichoic acids (51, 55), mycobacterial lipomannans and lipoarabinomannans (56), pneumococcal peptidoglycans (57), and Treponema-derived glycolipids (58). Thus, LBP and CD14 may function to disaggregate and deliver a variety of acylated microbial agonists to the TLR2 system.”  (Goodridge & Underhill, 2008). Although this may be jargain to the average person, the chart below can help people understand what antigens are specific to TLR 2 receptors and some of the agonists that affect how it responds to presenting antigens.
(TLR2, 2018)
OspA is Pam3cys, a triacyl lipoprotein (3 fatty acid chains)
Now that we understand how Pam3cys works, it is important to understand that it is similar in structure to OspA.
Scientists from the Immunobiology Research Institute published a study that found “OspA is a 30-kDa membrane-associated lipoprotein with a typical tripalmitoyl-S-glycerylcysteine (Pam3Cys) moiety covalently attached to the N terminus of the protein.”  (Goodridge & Underhill, 2008). Another study done by Heilbrun et al (2003) from the Department of Pathology, University of Utah, in Salt Lake City found that “OspA is one of the tripalmitoyl-S-glyceryl-cysteine (Pam3Cys)-modified lipoproteins abundantly expressed on the surface of B. burgdorferi in the gut of the unfed tick (1122).” (Heilbrun et al, 2003). Finally, in one of their many patents, Dattwyler, Gomes-Solecki & Seegers (2009) found that:
“The primary translation product of the full-length B. burgdorferi OspA gene contains a hydrophobic N-terminal sequence, of 16 amino acids, which is a substrate for the attachment of a diacyl glyceryl to the sulflhydryl side chain of the adjacent cysteine (Cys) residue (at position 17). Following this attachment, cleavage by signal peptidase II and the attachment of a third fatty acid to the N-terminus occurs. The completed lipid moiety, a tripalmitoyl-S-glycerylcysteine modification, is termed Pam3Cys (or is sometimes referred to herein as Pam(3)Cys or Pam3Cys)” (p.1).
As you can see, there are several credible studies that show that Pam3cys and OspA are very similar in structure. The lipoproteins are TLR 2/1 agonists (agonists are a substance that initiates a physiological response when combined with a receptor). TLR 2 agonists are fungal-like because they cause permanent immune suppression in the Toll Like Receptors that handle fungal antigens.

OspA/Pam3cys is managed by TLR2

As previously mentioned, OspA and Pam3cys are TLR 2/1 agonists. Heilbrun et al (2003) found that “Toll-like receptor 2 (TLR2) is a transmembrane signal transducer for tripalmitoyl-S-glyceryl-cysteine (Pam3Cys)-modified lipoproteins, including OspA from the Lyme disease spirochete Borrelia burgdorferi.” (p.2).  Furthermore, Pam3Cys-modified proteins, such as OspA, have been reported to act as potent inflammatory stimulants though the toll-like 2 receptor mechanism (TLR2)”  (Dattwyler, Gomes-Solecki & Seegers 2009). As confusing as this may sound to people who have no science backgrounds, what this means is that there is plenty of literature that proves that OspA/Pam3cys are managed by TLR 2.

OspA/TLR2 agonists are much more toxic and stealth than typical bacteria
One thing that important for activists to understand is that unlike sepsis caused by regular bacteria (managed by TLR 4 and is generally reversible), sepsis caused by TLR 2 agonists can cause permanent and irreversible damage.
More specifically,”TLR2 mediates inflammatory responses to a wide variety of lipidated microbial components, including bacterial lipoproteins, atypical lipopolysaccharides, and lipomannans (26–28). Among these microbial agonists, bacterial lipoproteins are by far the most potent  (Kelley, Ranoa & Tapping, 2013).  Moreover, “it became apparent that specific TLRs such as TLR2 and TLR4 play differential roles in the activation of the various arms of the innate immune response” (Kullberg, Meer & Netea, 2007). In the Journal of Immunology,   Akira, Hayashi, & Nobrega (2005) published a study whereby “experiments with TLR2-knockout mice confirmed that the inhibitory effects of Pam3Cys depend on the expression of TLR2” (p.6640).  Furthermore, their study concluded that “Pam3Cys keeps the precursors on a more immature stage” (Akira, Hayashi, & Nobrega, 2005). Taken together, the study done by Akira, Hayashi, & Nobrega (2005) “suggest that TLR4 signaling favors B lymphocyte maturation, whereas TLR2 arrests/retards that process, ascribing new roles for TLRs in B cell physiology.” (p. 6645).  In sum, there is plenty of research that shows that OspA/Pam3cys are TLR 2 agonists (fungal like) and cause irreversible/permanent immunosuppression.

OspA is the key mechanism to understand when it comes to Lyme Disease .
Now that we understand how OspA affects the host, the next part of this blog will use published evidence based literature that proves that OspA is the main driver of disease in Lyme patients.

Norman Latov - OspA vaccination caused the same chronic neurological disease as Lyme:  Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi.

"Neurological syndromes that follow vaccination or infection are often attributed to autoimmune mechanisms. We report six patients who developed neuropathy or cognitive impairment, within several days to 2 months, following vaccination with the OspA antigen of Borrelia burgdorferi. Two of the patients developed cognitive impairment, one chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy, one both cognitive impairment and CIDP, and one cognitive impairment and sensory axonal neuropathy. The patients with cognitive impairment had T2 hyperintense white matter lesions on magnetic resonance imaging. The similarity between the neurological sequelae observed in the OspA-vaccinated patients and those with chronic Lyme disease suggests a possible role for immune mechanisms in some of the manifestations of chronic Lyme disease that are resistant to antibiotic treatment."

Gary Wormser - OspA causes immunosuppression
(which means it was the opposite of a “vaccine”):  
"The modulation of human lymphocyte proliferative responses was demonstrated with a recombinant outer surface protein A (OspA) vaccine preparation for the prevention of Borrelia burgdorferi infection. After exposure to either the unaltered vaccine preparation or OspA prepared in saline, normal lymphocyte responses to the mitogens concanavalin A, phytohemagglutinin-M or pokeweed mitogen, or the antigen BCG were consistently reduced. Whole cell extracts of B. burgdorferi also modulated immune responses but required a much greater quantity of protein than needed for the OspA preparation. The magnitude of modulation was directly dependent on the quantity of OspA. OspA interferes with the response of lymphocytes to proliferative stimuli including a blocking of cell cycle phase progression. Future studies designed to delete the particular region or component of the OspA molecule responsible for this effect may lead to improved vaccine preparations."               

Donald H. Marks – an OspA vaccine trial administrator – LYMErix caused the same disease as chronic Lyme: 
"A wide range of neurological complications have been reported via the medical literature and the VAERS system after vaccination with recombinant outer surface protein A (OspA) of Borrelia. To explore this issue, 24 patients reporting neurological adverse events (AE) after vaccination with Lymerix, out of a group of 94 patients reporting adverse events after Lymerix vaccination, were examined for causation. Five reports of cerebral ischemia, two transient Ischemic attacks, five demyelinating events, two optic neuritis, two reports of transverse myelitis, and one non-specific demyelinating condition are evaluated in this paper. Caution is raised on not actively looking for neurologic AE, and for not considering causation when the incidence rate is too low to raise a calculable difference to natural occurence."  https://www.ncbi.nlm.nih.gov/pubmed/21673416

Ben Luft at the 1998 FDA Vaccine Meeting on LYMErix – You can't tell the difference between chronic neurological Lyme and LYMErix victims
  “The point that I wanted to make in regard to the study is that there is very heavy dependence on serologic confirmation. And when we start thinking about the adverse events, *** it was stated originally when we got the overview of the disease that the disease is really quite protean. And actually the adverse events are very similar to what the disease manifestations are.**** And if you start to, as I think Dr. Hall was eluding to — if you start to kind of say well how often do you actually become seropositive, you can start to have a different take on when someone has an adverse event or whether it is disease specific or infection specific versus vaccine specific. And I think that that is an important issue that we have to deal with.”  

OspA Patent: Dave Persing says this about the similarities between Lyme and LYMErix disease:
"Additional uncertainty may arise if the vaccines are not completely protective; vaccinated patients with multisystem complaints characteristic of later presentations of Lyme disease may be difficult to distinguish from patients with vaccine failure….”           

The NIH patent explaining how Lyme causes LYMErix-disease (“stealth bomber”):
“The invention relates to novel antigens associated with Borrelia burgdorferi which are exported (or shed) in vivo and whose detection is a means of diagnosing Lyme disease. The antigens are extracellular membrane vesicles and other bioproducts including the major extracellular protein antigen. Another object of the invention is to provide antibodies, monoclonal and/or polyclonal, labeled and/or unlabeled, that are raised against the antigens. A further object of the invention is to provide a method of diagnosing Lyme disease by detecting the antigens in a biological sample taken from a host using the antibodies in conventional immunoassay formats. Another object of the invention is to provide kits, for the diagnosis of Lyme disease, comprising the antibodies and ancillary reagents. The advantage of the antibodies used in the invention is that they react with the antigens from geographically diverse strains of Borrelia burgdorferi, but do not react with antigens from related Borrelia spirochetes.”  

Based on published NIH research studies, it appears that OspA tolerizes immune cells and impairs the immune system from responding to any antigens that are managed by TLR 2. In addition, OspA also causes cross-tollerance whereby the immune system is no longer able to recognize and fight off other viral, parasitic, and bacterial pathogens

Additional resoruces on Toll Like Receptors affected by Lyme Disease (OspA)
TLR4 agonists – lipopolysaccharides, known as the more typical bacteria.    https://www.ncbi.nlm.nih.gov/pubmed/23695305http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714565/
TLR5 agonists – Flagellins             https://www.ncbi.nlm.nih.gov/pubmed/16479520
TLR7/9 agonists – Herpesviruses, Epstein-Barr and all other viral infections.           https://www.ncbi.nlm.nih.gov/pubmed/22227568
As a result of counter transference, both viral and opportunistic infections reactivate and take over the human host.
OspA or TLR2/1 agonists are so toxic, that the body shuts down the immune system to avoid a septic cytokine storm. Xiong et al (2015) from the Department of Microbiology and Immunology at the University of Maryland School of Medicine found that “Endotoxin tolerance protects the host by limiting excessive ‘cytokine storm’ during sepsis, but compromises the ability to counteract infections in septic shock survivors” (p. 172). Further more, “it reprograms Toll-like receptor (TLR) 4 responses by attenuating the expression of proinflammatory cytokines without suppressing anti-inflammatory and antimicrobial mediators, but the mechanisms of reprogramming remain unclear” (Xiong et al, 2015).  In another study, researchers found that the “development of endotoxin tolerance following the initial cytokine storm phase of sepsis is thought to protect the host from an over exuberant immune response and tissue damage but at the same time, may render the host immunocompromised and more susceptible to secondary infection” (Medvedev, Pennini, Vogel, & Xiong, 2013). As you can see, the complexities of Lyme Disease go far beyond what mainstream activists let on.

Based of the research studies provided in previous paragraphs, it’s easy to see that spirochetes  are constantly undergoing antigenic variation by shedding their outer surface to avoid immune detection.
In addition, these shed blebs are covered in fungal-like Osps that have the ability to inhibit apoptosis and cause Post-Sepsis Syndrome in its victims.
Spirochetes travel to the lymph nodes, bone marrow, and the brain within the first week of infection where they shed these OspA “blebs” that get eaten up by immune cells.
As a result,  B-cell germinal centers are wrecked permanently and prevents B-cells from properly maturing (Leading to a reduction in detectable antibodies).
This leads to global immunosuppression in the blood and an immune system that is tolerized to opportunistic infections and reactivated viruses (Epstein-barr, HHV-6, cytomegalovirus, coxsackie, zoster, candida, mycoplasma, streptococcus, etc). All while also causing  inflammation in the brain.
In at least half the cases, Lyme Disease causes post sepsis and permanent B-cell immune disorders (Firbo, ME, CFS, GWI, etc.). Think of the spirochetes as just the detinator of this immunosuppressive neurologic nightmare.
Therefore spirochete persistence is not the main driver of disease in Lyme patients, it’s the exposure to fungal-like antigens (Osps/Pam3cys) that wreaks havoc in the human body.
In addition to OspA being shed by spirochetes, it was also used in the failed LYMErix vaccine. As mentioned before, you cannot vaccinate against relapsing fever organisms due to antigenic variation. Keep this in mind for the new vaccine that they are currently attempting to push through without it going through phase three of the trials.
Researchers concluded in the first vaccine trials, that the vaccine caused “defects in the TLR1/2 signaling pathway are associated with an impaired ability to generate antibodies following immunization with OspA lipoprotein” (Fikrig & Thomas, 2002). If you are an activist and want to see changes, you need to take this information seriously and protest this vaccine and attempt to stop it before it finishes phase 2 trials.
Being that OspA is the driving force behind Lyme Disease,  how convenient is it that the criminals left out OspA from the “case definition” at the same time the vaccine was on trial?
From the multitude of evidence based studies used to source this blog, it is clear that you cannot inject people with TLR 2/1 agonists because they cause immunosuppression and Post Sepsis Syndrome (B-cell immune disorders).
All fungal bearing vaccine attempts managed by TLR2/1 were epic failures causing the same outcome in which they “intended” to prevent (Tuberculosis, Brucella, HIV, Borrelia are parallel models in fungal-like vaccines).
OspA is Pam3cys = Permanent Immunosuppression = Oppurtunistic Infections = Tick Bite Sepsis
If OspA alone causes the same multi-system disease, what is the disease?

It’s important to note that these disease mechanisms are shared by many other abused groups (FM, ME, CFS, GWI, etc), and not all are caused by Lyme Disease.
They are caused by TLR 2/1 agonists that cause a fungal like sepsis that leads to permanent immunosuppression. There is nothing pseudoscientific about anything in this blog, as all the sources used are from ‘credible scientists’ from all over the world (many of which deny the severity of Lyme Disease).  In the end, we all need to unite to fight against the B-cell disorder (post sepsis) epidemic that is plaguing the world.
Dattwyler, R., Gomes-Solecki, M., & Seegers, J. (2009, December 31). 20090324638 LIVE BACTERIAL VACCINE. Retrieved May 25, 2018, from https://patentscope.wipo.int/search/en/detail.jsf?docId=US42934470&recNum=9&maxRec=30&office&prevFilter&sortOption=Pub Date Desc&queryString=tripalmitoyl cysteine or Pam3Cys and Epstein-Barr&tab=NationalBiblio
Akasaka, K., Tamura, A., Nakagawa, T., Koide, S., Huang, X., Link, K., & Koide, A. (1999). Multistep denaturation of Outer surface protein A (OspA). Seibutsu Butsuri, 39, 89-96. doi:10.2142/biophys.39.s163_1
Akira, S. A., Hayashi, E., & Nobrega, A. (2005). Role of TLR in B Cell Development: Signaling through TLR4 Promotes B Cell Maturation and Is Inhibited by TLR2. The Journal of Immunology, 174(11), 6639-6647. doi:10.4049/jimmunol.174.11.6639
Barbour, A. G., Todd, W. J., & Stoenner, H. G. (1982). Action of penicillin on Borrelia hermsii. Antimicrobial Agents and Chemotherapy, 21(5), 823-829. doi:10.1128/aac.21.5.823
Fikrig, E., & Thomas, V. (2002). The Lyme Disease Vaccine Takes Its Toll. Vector-Borne and Zoonotic Diseases, 2(4), 217-222. doi:10.1089/153036602321653798
Goodridge, H. S., & Underhill, D. M. (2008). Fungal Recognition by TLR2 and Dectin-1. Retrieved May 25, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/18071656
Heilbrun, M., Wang, X., Ma, Y., Philipp, M. T., Yoder, A., Weis, J. H., . . . Weis, J. J. (2003). Tripalmitoyl-S-Glyceryl-Cysteine-Dependent OspA Vaccination of Toll-Like Receptor 2-Deficient Mice Results in Effective Protection from Borrelia burgdorferi Challenge. Infection and Immunity,71(7), 3894-3900. doi:10.1128/iai.71.7.3894-3900.2003
Kelley, S. .., Ranoa, D., & Tapping, R. (2013). Human Lipopolysaccharide-binding Protein (LBP) and CD14 Independently Deliver Triacylated Lipoproteins to Toll-like Receptor 1 (TLR1) and TLR2 and Enhance Formation of the Ternary Signaling Complex. Journal of Biological Chemistry,288(14), 9729-9741. doi:10.1074/jbc.m113.453266
Kullberg, B. G., Meer, J. W., & Netea, M. J. (2007). Recognition of fungal pathogens by Toll-like receptors. Immunology of Fungal Infections, 23(9), 259-272. doi:10.1007/1-4020-5492-0_11
Medvedev, A., Pennini, M., Vogel, S. N., & Xiong, Y. E. (2013). IRAK4 kinase activity is not required for induction of endotoxin tolerance but contributes to TLR2-mediated tolerance. Journal of Leukocyte Biology, 94(2), 291-300. doi:10.1189/jlb.0812401
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