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Friday, December 12, 2008

Inside the Box

Physicians who treat Lyme disease have been accused of ignoring the proved science and working outside the box. I am at a medical conference for a week. I decided to buy a textbook. This behemoth 1500 page book called: Clinical Immunology- Principals and Practice was published this year- 2008. It appears to be the preeminent text on the subject. It was written for specialists in the field. Leafing through the pages of this tome is enough to give one vertigo. It is full of incredible information written in a language all its own, which is certainly intimidating to a non scientist like myself. Despite this, I have tried to make some sense of its relevance to the disease which is the perpetual obsession of this Blog- Lyme disease, of course.

I will attempt to transfer some relevant information to the reader. I have found that some of my prior comments were erroneous. I hope this will correct the record.
For the most part however, I have found validation of the concepts previously presented to a greater extent than I would have anticipated.

The immune system is magical. The book is broken down into chapters. I suspect that it is impossible to take in the breadth of knowledge presented here in a single glance. The immune system is highly complex, evolved and robust system. Nonetheless: "The vertebrate immune system is a product of eons of evolutionary struggle and their much less rapidly reproducing, and hence less adaptable, hosts." (Rich page 3).

Immune cells have pattern recognition receptors (PPRs). Everything in immunology has annoying acronyms which I sometimes think were put there to keep nosy neophytes, like me out of mix. These receptors on immune cells called T cells are necessary so that the immune system can distinguish things that belong (and not attack them), like your own cells, from things that do not belong like bacterial invaders. I have long suspected that some patients seem to have a natural immunity from developing Lyme disease after infection. Chapter 3, page 48 indicates that certain genes which regulate certain TLRs- Toll like receptors- a type of PPR, confer either susceptibility or resistance to Lyme disease. The incidence of these genetic variations is not mentioned.

The literature about Borrelia burdorgferi, the Lyme germ clearly indicates that it has both intracellular and extracellular forms. Chapter 25 deals with the immunology of intracellular bacteria. On pages 390-391 the authors make it very clear that with rare exception- intracellular bacteria cannot be eradicated from the host. The authors state that the intracellular environment provides a protective niche. Such bacteria are of low toxicity. The extent of disease frequently relates to damage caused by the immune response rather than the infection itself. The primary mode of attack involves the innate immune system rather than the acquired immune system.
One immune cell which "eats" foreign bacteria is called the neutrophil. This is a major actor in the immune system. Page 397, the neutrophils are inactive against intracellular germs, because they are inside cells. Nonetheless, the bacteria may enter the short lived neutrophils and use them as a "Trogan horse." The dying neutrophils containing our buddy (Lyme),as an intracellular germ, is "eaten" by a macrophage, which in a resting state has a long life, low antimicrobial activity and provides a good home for such germs. Many such bacteria live in a phagosome, a structure which would ordinary assist in their elimination, but intracellular bacteria may have the ability to escape into the cytoplasm, the main body of the cell, and enjoy a safe nutrient rich environment. These bacteria have also figured a way to transfer directly from cell to cell without venturing into the dangerous waters of the circulating blood stream. (Page 400). While much is understood about the production of protective antibodies against extracellular bacteria, little is known about (T cell) immunity required to protect against intracellular germs. B cells which produce the protective antibodies for extracellular germs have a minor role here due to the bacteria's "lifestyle." Page 403.

Chapter 26 actually deals with the immune response to spirochetes. So I had to buy the book. It does contain significant factual errors but is still a treasure trove of great information.

The Ixodes tick actively participates in the transmission of Lyme to the host. This is one reason why it is unlikely that other vectors, like mosquitoes transmit the infection. The tick secretes a protein (Salp 15) which inactivates host T cells, helper CD4 cells. Bb latches onto the beneficial protein via the Lyme OspC protein (associated with 23 band on WB), as part of an immune avoidance strategy. (Page 418). Lyme- Bb is a very smart germ. It comes with a daunting array of immune defeating weapons. It has 21 plasmids. These are extra pieces of DNA, not integrated into the nucleus of the organism. It's genomic structure (DNA) is able to recombine with the extra pieces of DNA and change it's structure to thwart the immune resposnes. One surface protein, Ops A is present when the spirochete is living in the tick's gut. It apparently is useful for bacterial attachment in this environment. A tick receptor protein TROSPA is involved. This acronym is frequently encountered. It simply stands for tick receptor outer surface protein A. As soon as mammalian blood, like ours is encountered it reduces OspA by ninety fold and produces OspC- the immune system avoiding protein. A neat trick! (Page 411).

Proteins are not the only structures to which antibodies can be formed. Lipids and carbohydrates can also be immunogenic, cause antibody production. Other spirochetes express lippopolysacharides on their surface. Borrelia is the only member of the spirochete family which does not do this. It does not engage Toll like receptor 4. It is not clear how this effects the overall immune response. It's variable responses to TLRs 2 and 4 is mentioned and this seems to have an effect on limiting immunological responses to Bb. (Page 415)

Lyme has mechanisms to evade the complement system which is a main effector mechanism for the destruction of bacteria. (Page 416)

I seem to have gotten the Th1 and Th2 issue somewhat confused. While the Th1 mechanisms is essential in the control of intracellular infection, The Th2 mechanism is essential for the antibody response of B cells and immunoglobulin switching. The shift towards a Th1 response seen with Lyme infection actually results in more inflammation and less antibody production. (Page 417) Is this because the immune system is confused since it is dealing with both an intracellular and an extracellular infection- my own conjecture.

My last comments relates to statements on page 418. Antibodies against OspB (Band 34) can be thwarted by a mutation of this protein which removes a lysine amino acid.
Lyme can attach to intracellular matrix proteins such as decorin to avoid detection by the immune system. Lyme can acquire host antigens- from our cell, to avoid the immune system. And Lyme can constantly change it's surface proteins giving the immune system a run for its money. Finally, one example is given of how Lyme can recombine genomic DNA and plasmid DNA to alter a specific surface protein antigen.

Believe it or not, this blog has omitted 95% of the arcane details of the immunological mechanisms. I have here tried to offer some simplified information.

This information is right off the pages of the most current text in immunology. Ostensibly it is information with which IDSA members should be intimately familiar with.

Inside the box data would seem to provide biological support for the notion that 14 days of antibiotics would frequently be ineffective against Lyme disease. This contradicts "facts" presented in the 2006 IDSA guidelines.


BryanR said...

I couldn't find your contact info so I am asking this question here: Blog owner: do you mind if I share a link to your blog in my next email newsletter? Thanks, Bryan, theskyking -at-

jack said...

Be careful with whom you are linked to or associated with, LymeMD.

Anonymous said...


I would like some advice on tx options. I appreciate this blog and the doctor's insight and advice. I would also like to know how I can consult with him, and appropriate contact information.

After 1 year of severe fatigue and chronic infections, My 13 YO son has been diagnosed with Primary Immune Deficiency. His labs showed IgG subclass deficiency, and very high strep,rubeola, and HHV6 titers. Based on labs and clinical picture, he was put on IVIG, and has been on it for 6 months now.

The IVIG has helped him a lot. He is much more functional now, but it is a fragile state and he is still very ill.

We have long suspected Lyme, and a LLD thinks he is Lyme positive based on clinical picture. He was recently tested through Igenex and came back with band 34 positive, and 31 and 41 indeterminate.

His immunologist doesn't care about Lyme. His GP who is a naturopath and is not LLD thinks we should provoke him with antibiotics to try and get a definitely positive test.
He is IgG deficient and is also on replacement therapy so I don't know how likely it is that we could get an accurate antibody response.

Where do we go from here???

Thanks for any feedback.

dogs name said...

My husband is being treated for Lymes and babesia and also an unknown bacteria in his blood. He had a spinal tap done for the second time in the ER (thats the ER for you) and when it was done they blotched it up by using the same needle and going in twice. This produced a result with blood in his spinal fluid. Is it possible that the unknown bacteria has now found its way into his spinal fluid. He is experiencing severe headaches, spinal pain, neck pain and his knees feel like they are going to rupture. What is your opinion that this has happened now? He is much worse even after 3 months of treatment.

Lyme report: Montgomery County, MD said...

I am a family doctor with an interest in Lyme disease. I am a member of ILADS. ILADS is a professional organization which promotes a particular point of view. My biases are in line with many of those described in ILADS published guidelines.

The purpose of this blog was primarily to share many of my ideas with my patients.

I still believe that there is much that we do not know about this illness. Perhaps we have only scratched the surface. Nonetheless, I obviously disagree with the mainstream views expressed by the IDSA and many mainstream texts and publications.
I from time to time have attempted to point out that there is a body of scientific evidence which provides support for the alternative view.

I am convinced that my clinical results have been very favorable for most of the patients I treat.
I can not refute the argument that anecdotal- clinical experience is a substitute for randomized controlled clinical trials. As I have tried to point out there does exist a body of scientific evidence including clinical trials which support the ILADS ideas.

I feel that my patients are frequently critically ill and that I do not have the luxury of waiting for the "science" to catch up with the clinical experience of those who do treat Lyme disease.
One can debate the quantity and quality of science which exists at this time.

As a physician, my primary job is to do my best to help patients, while at the same time avoiding potential risks and pit falls. Patients need to fully informed regarding the controversies and differing opinions.

I offer this as informational only.
Google offers BLOGs without any charge. I am selling nothing and have no financial interests in writing this BLOG. If anything, some have criticized me for giving away information for free. I do not agree with this view.

I have no connections or represenations. The ideas promoted here are strictly my own. When I present fact I do my best to make sure I am accurate. I am sure I have made some factual errors along the way. There is no editing or fact checking process.

This specifically is not written for purposes of offering medical advice. Medical advice can only be obtained from treating physicians.

I do not claim to be an expert in Lyme disease. It is my bias that no such experts exist at this time. This is new and evolving area of medicine, which remains largely unrecognized- in my opinion.

I am not an immunologist or specialist in any particular area of medicine. I am a board certified family practitioner with over 20 years of experience.

If readers make comments they may be useful to other readers. I welcome appropriate comments.

In general I am unable to answer specific questions. I can make general suggestions and offer ideas at times. I can not respond to most questions.

It would be my preference if readers would comment on specific BLOGS rather than asking specific questions about their particular cases.

Thank you

Lyme report: Montgomery County, MD said...
This comment has been removed by the author.
dogdoc said...

Lawyer finally made an impression did he? This is good actually- you have to be careful with being seen as giving specific medical advice. That is a no- no. Your blog is interesting and helpful to us just on its own. To all who wish specific advice- I suggest they make an appointment. You can call Barbara at ILADS for a reference. I am not you so I can say that legally. (smile)

Michele said...

I am concerned about your safety and reputation. My comment is the same as Jack's. Be very, very careful whom you are linked with and who you associate with. I have no other motive than your well being and keeping you as my doc.