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RA drugs may further damage immune system
Lyme Disease Vaccine and Bell Palsy
Transfer Factor Successes
INCREASED BLOOD VISCOSITY DUE TO SOLUBLE FIBRIN MONOMER.

Note: "OspA" is "outer surface protein A"

August 3, 2000

Bacteria Hide Out in Tiny 'Caves' in Cells

By Alka Agrawal

NEW YORK (Reuters Health) - US scientists have found that bacteria can hijack a cellular structure to get into immune cells and hide from the body's defenses.

The structures, known as ``caveolae'' because they look like little caves, are normally used to transmit signals within cells, Dr. Soman N. Abraham of Duke University in Durham, North Carolina, told Reuters Health. When bacteria enter cells, they normally enter compartments that later fuse with other cell structures, called lysosomes, which kill the bacteria.

But since caveolae do not fuse with lysosomes, ``we've discovered a route of entry of bacteria that avoids the killing activity of the host cell,'' Abraham said. ``So this is a neat way that bacteria can avoid being killed by the very immune cells that are there to kill them. Once they're in here, they can obviously avoid antibiotics, they can avoid other immune cells.'' ...

As they report in the August 4th issue of Science,

SOURCE: Science 2000;289:732-733, 785-788.

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Tuesday, August 1, 2000

Study May Force Re-Think on Rheumatoid Arthritis

WASHINGTON (Reuters) - People with rheumatoid arthritis, who have long been thought to have overactive immune systems, instead may have exhausted immune systems, researchers said on Tuesday. ''What this study has shown for the first time is that patients with rheumatoid arthritis have prematurely aged immune systems,'' lead author Dr. Cornelia Weyand, a rheumatologist at the Mayo Clinic in Minnesota, said in a statement.

''Until now we have thought that these patients had overactive immune systems, which is why we have aggressively treated the symptoms of rheumatoid arthritis with medications that suppress the immune system,'' said Weyand, whose findings were published in the Proceedings of the National Academy of Sciences.

''While this practice offers relief of the painful symptoms, it also puts patients at greater risk for infections and cardiovascular disease -- the two leading causes of death among these patients.''

Scientists estimate about 2.1 million Americans have rheumatoid arthritis -- most of them women ...

Weyand and colleagues ... found that the T-cells -- the immune cells that are programmed to recognize and attack invaders such as bacteria and viruses -- were worn out. ''They do not make new T-cells,'' Weyand said in a telephone interview.

One of the strengths of the human immune system is the large repertoire of so-called memory T-cells, which can recognize hundreds of different strains of cold viruses, streptococcal bacteria and thousands of other microbes.

As people age, this repertoire gets smaller, which is one reason why older people are more at risk from diseases such as influenza and food poisoning.

IMMUNE SYSTEMS LOOKED 30 YEARS OLDER THAN PATIENTS

Weyand's team found that young rheumatoid arthritis patients had many fewer different T-cells than they should have. Patients 20 to 30 years old had a collection of T-cells that looked like they belonged to 50- to 60-year-olds.

And the chromosomes in the cells, which are the structures that carry the genetic material, were frayed. Chromosomes are capped with telomeres, which get a little worn with each cell division. The telomeres in the T-cells were worn away.

Weyand said it appeared the thymus glands in the patients --where T-cells get their ''education'' -- were not working properly and too few T-cells were being produced ...

This could mean that current rheumatoid arthritis drugs that target the immune system may be missing the boat ...

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The Lyme Disease Vaccine: Implications for Bell Palsy

Ivan Oransky, MD, Ankur Saraiya, MD, Yale-New Haven Hospital, New Haven, Conn; Columbia University College of Physicians and Surgeons, New York.

[Infect Med 17(6):456-457, 2000.]

With the approval by the FDA of a vaccine against the causative agent in Lyme disease, some experts believe that the incidence of Bell palsy will decrease. This conclusion is based on data suggesting that many cases of Bell palsy are in fact undiagnosed cases of Lyme borreliosis.

Lyme disease, named for the Connecticut town where a cluster of cases was first reported in the late 1970s, is a multisystem inflammatory disorder that often produces a distinctive target-shaped primary skin lesion.[1] Newly diagnosed cases number between 15,000 and 20,000 annually.

The syndrome is characterized by nonspecific flu-like symptoms (acute fe- brile illness with headache, malaise, fatigue, mild stiff neck, or muscle aches) with associated development of new-onset arthralgias, myalgias, and neurologic symptoms.[2]

Symptoms follow infection by the spirochete Borrelia burgdorferi which, in humans, is transmitted through bites of ticks of the genus Ixodes. The flu-like syndrome is later followed by neurologic and cardiac symptoms.

Aside from headache, the most common neurologic symptom associated with Lyme disease is PERIPHERAL FACIAL PALSY, (PFP), occurring, according to one report, in 11% of patients with Lyme disease.[3] There is evidence, however, that the incidence of Borrelia-associated PFP is much higher and that many cases of idiopathic facial paralysis, known as Bell palsy, are actually manifestations of undiagnosed Lyme borreliosis.

For example, in some cases, acute PFP is the only symptom of Lyme disease but, because the syndrome is more commonly characterized by a distinctive rash with a history of tick-bite, a Lyme disease diagnosis can be overlooked in favor of the diagnosis of Bell palsy ...

In regions where Lyme disease is endemic, physicians have a better familiarity with the disease and a higher index of suspicion for the infection when faced with the symptom of PFP. In areas where physicians do not regularly see Lyme disease, an isolated acute PFP might more likely be diagnosed as Bell palsy ...

[Findings of Ikeda et al[5] suggest that 32% of cases of Bell palsy are caused by B burgdorfer.] It is quite possible that the 32% figure is an underestimate of the true seroprevalence. Because the antibody response to Borrelia infection is slow, serum measurements are sometimes taken before detectable levels of antibody have had sufficient time to develop.

The implications of the relationship between Lyme disease and idiopathic PFP are not merely academic. Lymerix (SmithKline Beecham, Philadelphia), a vaccine against Lyme disease, was given approval by the FDA in December 1998.[7]

The effectiveness and tolerability of the vaccine, which consists of recombinant outer surface lipoprotein A (OspA) of the Zs7 strain of the B burgdorferi spirochete, was established in 2 double-blind studies, each with more than 10,000 patients, published in The New England Journal of Medicine in 1998.[8,9]

Early work, which led up to the vaccine's approval, was fraught with sometimes counterintuitive findings. Despite the fact that free antibodies to OspA are not detectable in early stages of the disease, preliminary animal studies had shown that antibodies against OspA were protective against Lyme disease. Early clinical trials also demonstrated that recombinant OspA was well tolerated and able to generate an immune response in animals.[9]

Designing studies to investigate the efficacy of a vaccine in humans, however, presented several problems. Even in areas where the disease is endemic, attack rates are highly variable and depend on each subject's exposure to deer ticks at specific times of year. Furthermore, the disease itself has a very diverse array of symptoms and a variable time course.[10]

To overcome these difficulties, researchers incorporated a number of coordinated administration schedules and clinical tests to determine the most effective ways of offering the vaccine. They found that the vaccine works optimally when given in 3 30-g doses. The initial dose is followed by a second dose after 1 month and a third booster dose after 1 year.

Once antibodies develop, they are doubly protective. First, antibodies are ingested in the tick's blood meal and can kill B burgdorferi in the tick's midgut. Any organisms that survive and are transmitted to the immunized host can be killed shortly thereafter.[11][8][9] ...

Based on the limited data currently available, it is unclear how much impact the vaccine against Lyme disease will have on the incidence of Bell palsy. According to the initial studies, the new vaccine can be expected to prevent about three quarters of potential cases of Lyme disease.

If the findings of Ikeda et al[5] suggesting that 32% of cases of Bell palsy are caused by B burgdorferi are correct, then it can be expected that roughly a quarter (24%) of the 23 cases of Bell palsy per 100,000 population might be prevented.

This optimistic interpretation of the data assumes that there is a direct, causative link between Lyme disease and PFP. Because the pathogenesis of Lyme disease-mediated PFP is not well understood, it is not certain that a vaccine will prevent the symptom. There is some indirect evidence that Lyme disease-associated PFP is alleviated by antibiotics,[12] suggesting that such a direct link exists.

However, PFP has been observed to emerge after antibiotic treatment has been initiated.[13] One hypothesis maintains that acute PFP, especially in children, is caused by direct neural invasion by the spirochete, which would occur before antibodies induced by a vaccine are able to isolate and kill the organism.

An important factor to consider when forecasting how many cases of Bell palsy will be prevented by the Lyme disease vaccine is that the vaccine is not yet approved for use in children younger than 15. Borrelia infection is responsible for a higher proportion of PFP in children than in adults.[14] Once the vaccine is approved for use in patients younger than 15, the rate of Bell palsy will likely decline.

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Source: Life Works (the_system2003@yahoo.com)
Subject: [Lyme-Aid] Transfer Factor Successes
Date: Sat, 29 Jul 2000

An update on some of the recent successes using Transfer Factor and Transfer Factor Plus as an immune boosting supplement to help address Lyme and other infectious agents.

This is forwarded by David Markowitz, MD, a pediatrician in Maine who has been using TF in his clinical practice for about 18 months with excellent results

"A 17 year old with bilateral facial palsy (Bell's Palsy) presented to us last week, with a diagnosis of Lyme Disease as the causitive agent. Traditionally, this paralysis lasts weeks to months. He had already been started on steroids by another doc without any change. We immediately started him on antibiotics and high dose TF+ (3 caps four times daily) to give his immune system a major boost.

By the way, Dr. Ken Singleton in MD has used either TF or TF+ in many Lyme patients with great success.

This was my first of the hundreds of kids we have started 4LR products to have Lyme Disease. Within 24 hours, this teenager had dramatically improved energy and stamina and a suggestion of a positive change in his palsy. Four days into boosting, one side of his face was at 75% of normal and the other had regained 25% function. Now a week later, he is at about 80% on both sides. I had hoped for some positive change but nothing like this. Be Well."

David Markowitz, MD

If anyone would like more detailed info about Transfer Factor and Transfer Factor Plus, contact Ron Santoro, Member, American Nutraceutical Association

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IMMUNE SYSTEM ACTIVATION of COAGULATION (ISAC)

Blood Coagulation and Fibrinolysis 1999: 10 435-438.

"Chronic fatigue syndrome &/or fibromyalgia as a variation of antiphospholipid antibody syndrome: An explanatory model and approach to laboratory diagnosis."

By Berg D, Berg LH, Couvaras J, Harrison H.

The model proposes that a majority of individuals diagnosed as having chronic illnesses, based on clinical criteria, may be potentially defined as having an AntiPhospholipid Antibody Syndrome with the endothelial cell as the disease target.

These patients have a hypercoagulable state demonstrated by increased markers of coagulation activation and INCREASED BLOOD VISCOSITY DUE TO THE GENERATION OF SOLUBLE FIBRIN MONOMER.

The Chronic Fatigue Syndrome / Fibromyalgia process may be triggered by a variety of pathogens (CMV, HHV6, Mycoplasma, Chl. pneumonia, etc.), resulting in pathogen-mediated immune activation that induces antibodies which cross react with Endothelial Cell protective proteins B2GPI & Annexin V.

These antibodies dislodge the protective proteins from Endothelial Cell surfaces, exposing PhosphatidylSerine on the Endothelial Cell surfaces in capillary beds.

Pathogens induce inflammatory responses which include cytokine modulation of Endothelial Cells to down regulate the antithrombotic environment in favor of prothrombotic expression of Tissue Factor.

Tissue Factor and PhosphatidylSerine exposure allows binding of the coagulation tenase and prothombinase complexes to Endothelial Cell surfaces. This results in thrombin generation leading to Soluble Fibrin Monomer formation.

Soluble Fibrin Monomer dimerizes easily, INCREASING BLOOD VISCOSITY and precipitating out on Endothelial Cell surfaces as fibrin(oid) deposition, creating local ischemia and pathology, blocking nutrient and oxygen delivery in the microcirculation.

A hereditary defect in a coagulation regulatory protein, such as protein C, protein S, Factor VL, prothrombin gene mutation, PAI-1, Lp(a), or elevated homocysteine is predispositional in greater than 75% of patients.

Because this hypercoagulability does not result in an immediate thrombosis (100% occlusion), BUT RATHER IN FIBRIN DEPOSITION (50-95%), we suggest that an appropriate name for this antiphospholipid antibody process would be IMMUNE SYSTEM ACTIVATION of COAGULATION (ISAC) syndrome.

This model provides an explanation for the therapeutic benefits reported with low dose anticoagulant therapy (heparin or warfarin) in the majority of chronically ill patients.

People are not chronically ill unless there is a coagulation regulatory protein defect as seen in Thrombophilia or Hypo Fibrinolysis.

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