I may add and repost to this entry a few times - stay tuned.
1) I looked at this part of the summary on Dr. Reinhard K. Straubinger's talk on “Canine and Equine Lyme Borreliosis” focused on Lyme borreliosis in animals, especially in dogs and horses:
"The highly variable surface protein VlsE is, according to current knowledge, exclusively expressed in the mammalian host. The invariable region IR6, and even a shorter peptide sequence of IR6 called C6 were found having a high potential as specific antigenic components in serologic test systems. This was shown by evaluating sera from infected humans, dogs, monkeys and mice. In experimentally infected dogs, C6-specific IgG antibodies appeared 3 weeks post infection; hence almost one week earlier than antibodies detected with ELISA based whole-cell preparations. Additionally, another benefit became clear when testing sera of people and dogs before and after antibiotic treatment. Contrary to antibodies against whole-cell components, research demonstrates that C6-antibodies declined substantially a few months after treatment. However, in animals with low C6-antibody levels prior to treatment, the decline obviously was minimal post treatment. Despite their high specificity for borrelial contact, C6-antibodies do not necessarily correlate with clinical signs in dogs and false-positive results may result from maternal antibodies in puppies born to infected bitches."
It brought to mind the following paper and a passage within it:
Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation. Stefan S. Tunev, Christine J. Hastey, Emir Hodzic, Sunlian Feng, Stephen W. Barthold, Nicole Baumgarth.
"We did not include the VlsE protein in our studies, a surface-protein thought to subvert the immune response to B. burgdorferi through extensive genetic variation within the host. However, the N40 strain of B. burgdorferi, which we have used here, does not seem to express this protein, based on transcriptional analysis of the IR6 region of vlsE. Moreover, we found no evidence of seroconversion to the C6 antigen of vlsE from strain B31 (S. W. Barthold, unpublished). Recent sequence analysis of the N40 genome has confirmed that N40 vlsE and BBK01 are on different plasmids and that the vlsE locus is indeed significantly different compared to B31, the commonly used VlsE-expressing Borrelia-strain."
So what do we know about C6 tests, briefly?
C6 Lyme ELISAs are based on the synthetic peptide C6, which corresponds to the invariable region IR6 of the surface antigen VLsE.
IR6 is supposed to be highly preserved in all pathogenic strains of Borrelia, and is only expressed in vivo. It evokes a strong immune response.
As a diagnostic antigen, the C6 peptide shows only minor cross-reactivity to other pathogens (e.g. spirochetes for syphilis).
Knowing this, it's interesting to point out that using the C6 ELISA may not work as well for testing a host which is infected with a strain of N40 Borrelia. How can it, when this strain of N40 does not express the vlsE protein?
I have to wonder how many other strains may have vlsE on different plasmids - and not only that - a different locus?
2) Dr. John Aucott’s talk on “Early Lyme disease” reported from the SLICE prospective cohort and his Maryland studies. I want to point out this part of the summary:
"He emphasized that the classic description of a “bull’s eye rash” occurs only 20% of the time – it is not the most common manifestation of the Lyme rash. Rather, a uniformly red or reddish-blue rash, round or oval in shape, with sharply demarcated borders is most common. Most often the rash develops in places such as the knee, groin, or arm pit, occurring at prime tick season, such as the late spring and early summer."
It's important to know that these varied descriptions of so-called "bull's eye" or EM rashes found in Lyme disease are not the only variations found in Lyme disease culture positive lesions.
In an earlier entry about Dr. Vijay Sikand's testimony at an FDA Lymerix Vaccine Review, Dr. Vikand reported this about EM rashes:
"[...] However, erythema migrans is not a single beast. Certainly this is the one which we easily recognize and which I just referred to.Before I continue with further slides, let me point out that the erythema migrans lesions you are about to see are all biopsy lesions which were laboratory proven to be caused by Borrelia burgdorferi.
Sometimes erythema migrans can present as a pustular lesion as is this one in the popliteal fossa inviting the scalpel of a surgeon.
Sometimes the lesions are vesicular in nature, inviting a diagnosis perhaps of herpes simplex infection.
Sometimes our round lesion is actually triangular.
Sometimes it doesn't even look round or red at all and invites a diagnosis of an intertriginous fungal infection in the groin of this patient who was biopsied and proven to have Lyme disease.
Sometimes the lesion is more plaque-like, inviting diagnosis of nummular eczema, psoriasis, or other similar lesions.
Sometimes it is in unusual locations.
Sometimes it is large like this one. Sometimes it is small with satellite areas. Sometimes it is multiple, appearing almost like urticaria or erythema multiform.
Sometimes, as in this individual who was a placebo recipient in the Lyme 008 SmithKline Beecham trial, it presents with other manifestations of early dissemination. This individual came in mainly because he was concerned about his face and it felt kind of funny and it was weak on one side. When I asked him whether he had had any unusual rashes, he said oh do you mean this one, and he showed me his arm with that EM. This is simply to illustrate the infranuclar 7th nerve palsy with which he presented. This patient, by the way, had no history of a tick bite or any unusual antecedent illness which he could remember."
If Sikand's testimony is anything to go on, one has to wonder about the reliability of the "bull's eye rash" as a diagnostic marker.
(For what it's worth, my own EM rash was large, oval, dark red, slightly elevated, and expanding for several days after the bite.)
3) Dr. Karen Newell Rogers presented a talk about novel ways to target chronic inflammation and chronic immune activation among patients with chronic Lyme disease.
Now this part below - especially in bold - really caught my eye:
"[...]Some researchers would argue that chronic inflammation requires the continuous presence of bacteria, whereas others would suggest that continuous presence of bacteria does not always result in inflammation and that exacerbations of chronic symptoms could result from infection with a different organism--or that chronic symptoms could re-cur from unrelated pro-inflammatory events. Potentially reconciling these seemingly conflicting perspectives on the mechanism of Lyme disease may be the effect of Borrelia burgdoreri’s bacterial by-products on Toll Like Receptors, (TLR)-mediated immune activation. TLR appear to be the “gate-keepers” of an inflammatory response. Bacteria, including Borrelia, produce products that, by binding to TLRs on the cell surface, promote leukocyte activation, cytokine production, and acute inflammation. In some genetic backgrounds of mice, acute inflammation is sufficient to fight off infection and resolve disease. In other mouse strains, the pathogens, or in this case the bacteria, get past TLR-induced inflammation and remain symptomatically undetectable in cells and tissues (Barthold, etc); Barthold et al. have found that no matter how severe or mild the disease in any of the genetically inbred strains of mice, there was no more inflammatory disease when the bacteria were eliminated."
Reading this, I reflect back on an earlier entry I made about the combination of genetics effect on individual immune systems AND persistent infection as both leading to ongoing symptoms in hosts:
Immune + Infection = HLA-DR alleles determine responsiveness to Borrelia burgdoferi:
Perhaps part of the answer to what is happening with ongoing symptoms lies both in Dr. Newell Rogers' work and Bettina Panagiota Iliopoulou, Mireia Guerau-de-Arellano, and Brigitte T. Huber's research?
It's certainly thought-provoking.
And Barthold's statement implies that ongoing inflammation is intimately tied to persisting infection.
How does one provide evidence this is the case?
Could the answer lie in longer term in vivo GFP and/or iRFP studies on mice and other mammals? Could it lie in maltodextrin enhanced imaging studies? Or something else?
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