The Tipping Point.....When you've fallen into the autoimmune bucket.

Infections play a significant roll in the development of autoimmune diseases. As I've mentioned before, the immune system begins to fatigue and ultimately fails to function normally. Multiple factors can contribute such as environmental exposures, toxins and genetics. The notion that infections are the culprit for the downward spiral can be found peppered throughout immunology and rheumatology research. Lyme disease and other tick-borne illnesses fit well within this mold.

As the immune system fails, it no longer recognizes "self" and begins producing auto-antibodies which perpetuate the cycle and continue to damage cells. This damage triggers inflammation which drives all autoimmune disorders creating  a vicious cycle of symptoms.

Autoimmune disorders play a major role in a person's ability to heal. Certain genetic markers that determine the body's ability to detox, methylate and break down inflammatory markers contribute. MTHFR, COMT, CBS, SOD, VDR are some of these relevant genetic markers. Genomix is a wonderfully relevant genetics testing company. I use them often to test patients.

Specific markers, HLA-DR4 and subsets within are strongly linked to a process called "molecular mimicry" . There are multiple avenues by which a pathogen can create autoimmunity in a host and this is one of them. Molecular mimicry occurs when a pathogen carries amino acid sequences similar to self-peptides leading to cross-reactivation of auto-reactive T and B cells. The pathogen acts as a self "mimic" . As a result, the activated T and B cells are also cross reactive with self and cause direct damage to its own cells.

An example of molecular mimicry is the development of Rheumatic fever following a streptococcal infection. Multiple studies show myosin to be the major autoantigen in the heart. When exposed to strep, cross reactivity between proteins of the streptococci and the "self" proteins occur causing an autoimmune response.

Another pathway is via epitope spreading where a persisting infection/antigen leads to an ongoing immune response causing tissue damage. When this occurs, further antigens are released and are taken up by antigen-presenting cells or APCs.  Antigen-presenting cells contain antigen complexes with histocompatibility complexes on their surfaces. Examples of these APCs are dendritic cells, macrophages and B cells. These in essences are accessory cells that assist in breaking down antigen proteins, creating peptides and presenting them on the cells surface so that T cells may  recognize them and ingest them. In a chronic or persistent infection scenario, eventually the  immune response becomes dysfunctional and serves its own cells on a silver platter for T cells to attack. 

Persistent Lyme disease via molecular mimicry and epitope spreading are shown in multiple human and animal models. Specifically, T-cells respond to the outer surface protein A of  Borrelia Burgdorferi and higher incidence of cross reactivity occurred with those that had the HLA markers. Outer surface protein A also  cross reacts with central nervous system proteins, creating neurological inflammation. This could explain why some people recover from the symptoms of Lyme disease and others develop chronic inflammatory driven illnesses that in many cases lead to  infectious triggered autoimmune encephalopathy and other autoimmune conditions despite antibiotic treatment.

I realize the subject matter is rather heavy for a Monday morning but bare with me. It's important to understand what is occurring in your body if you suffer from Lyme or other persistent infections. Many if not most symptoms described are interconnected and stem from the same process.  Knowing how the body may respond and understanding the nature of the antigen drives treatment options and ultimately determines if you will recover.  I utilize a barrage of antibiotic combinations while teasing in herbals, dietary restrictions and other modalities that will drive down inflammation, detox and alkalinize the body and temper T cell function ultimately treating the entire process. If treatment focus is just upon " killing the bug",  you've already lost the battle....

 

 

 

The Immune System is a dude.....

I hope that you all enjoyed my last let's talk lyme blog about PANS and the Lyme connection!

I know the many references explaining Lyme disease out there but for the sake of this blog, I feel it necessary to lay groundwork to provide deeper understanding of the disease and why perhaps it is so often missed in lab work.

The  immune system being a dude is tongue-in-cheek and meant to be taken lightheartedly. No dig on my male counterparts, you are all loved and respected! By nature men tend to complete a task before moving onto the next and do so expertly! Or so I'm told by my husband. Multitasking is another beast. Some can but as a collective group, men do not multitask well. 

Those of you entrenched in treatment with your children or perhaps yourself have witnessed shifting laboratory results. Many people have a multitude of symptoms with relatively "clean" labs while others may show multiple band on a Lyme Western Blot or other tick-borne diseases and feel perfectly fine at the moment.  You begin treatment, many feeling better but your repeated labwork looks worse! I have many patients with a perplexed gaze and state "but I'm better or my child is better! How can the labs be worse?"

I sum it up in one phrase, "The Immune system is like a dude." I usually get a chuckle or two with that comment.

What I mean by this is simply the immune system can only identify and recruit an aggressive assault on very few antigens at a time. It is horrible at multitasking especially when it can not "see" the antigen. When the immune system finds itself overwhelmed, it simply tucks the bacteria or virus away, not producing antibodies to it because it simply cannot deal with multiple insults effectively.

Simply stated, the immune system response occurs as T cells typically activate first utilizing T helper cells when an antigen is sensed as the initial immune response. This cascade effect of activation triggers other T cells that differentiate to perform specific functions as needed to abate an infection. The end result typically is B cell activation that then produce antibodies or "memory" of the antigen as well as plasma cells. This explanation is severely simplified as the immune system response is highly advanced with interconnected processes. What's important to know is the immune system's relationship with the unique nature of the spirochete that causes Lyme disease.

If the immune system's response is so robust how could Lyme disease possibly out maneuver it?

When a tick bites its victim, the spirochete that causes Lyme disease is passed thru the tissues. Released with the spirochete, the tick passes saliva as well which contains a film like substance.  This film coats the spirochete as it enters the body rendering it invisible to the immune system.  T cells are not activated initially and the immune system remains at a steady state. The spirochete has a unique structure called a flagellum, a tail-like structure. This structure helps propel the spirochete thru tissues and mucous that would typically stop the organism.

The movement of the flagellum stimulates the immune system, activating the T cells and triggering a full immune cascade. Given the constant movement of the spirochete and its stealthy shapeshifting mechanisms, the immune system is blind. As the immune system's B cells form antibodies to the original antigen identified, the spirochete has the ability to change its outer surface protein antigen to further evade death.

Knowing the antigen is still active, the immune system continues to mount a blind assault only creating extensive inflammation in the body and causing cell/tissue damage without effectively touching the spirochete.

As the inflammation mounts, further damage occurs to the skin, joints, brain and nerve endings. The full immune response intensifies the inflammation by creating toxic compounds and by-products. This would explain the widespread and varying symptoms that many patients describe.

As the immune system begins to fatigue and the spirochete lingers, structural mutations and abnormalities in the lymph tissues occur. These are the "germinal centers" and key in producing B cells or memory cells that create lasting antibodies. This would explain why a person may experience ongoing symptoms after a known exposure but have lab results that do not reflect it. The immune system is now dysfunctional and cannot produce the necessary antibodies that typical bloodwork would detect.

This is a very simplistic explanation of the immune response with Lyme disease and other co-infections. Essentially to give you a sense of what is happening in the body and why symptoms are experienced. There are many layers that determine each individual's experience with tick-borne illnesses and response to treatment.

 

PANS and Lyme connection?

Far too often I evaluate kids with abrupt mood and cognitive changes. As I dig thru their histories and interview parents, many times I find a tick exposure. Lyme disease and other tick-borne illnesses bring a borage of physical symptoms all too familiar. Of course I'm looking for other underlying causes as well and never assume that everyone has Lyme Disease. An undeniable trend is the connection between behavioral changes in children and tick-borne illnesses. Those not privy to the "Lyme world" are unaware of the cognitive and psychological components involved. Children account for about 25% of those diagnosed and are the highest risk groups. As a result of exposure, children suffer more from cognitive and social impairment, executive processing disorders, ADHD, dyslexia, irritability, expressive aphasia, short-term memory issues all which can be misdiagnosed! Within the context of cognitive and behavioral changes, there lies an acute syndrome that can occur as a result of Lyme disease or other tick-borne illness exposures known as PANS.

To give you a little background, the spirochete B. Burgdorferi that causes Lyme Disease has an affinity for the central nervous system. Studies have isolated this spirochete  in cerebrospinal fluid as early as 18 days after a tick bite. Other studies show this stealthy little spirochete's ability to punch thru endothelial cells and invade glial cells that surround neurons in roughly 12 hours. This invasion provokes an immune response followed by a sizeable inflammatory cascade event. Mast cells residing in the central nervous system are activating releasing cytokines and other inflammatory markers. The brain does not like inflammation! Once this occurs, symptoms of OCD (obsessive-compulsive disorder), anxiety, tics, short term memory recall difficulties, cognitive decline including fine and gross motor skill occur. No two symptom clusters are the same, however notable changes do occur.

An interesting morsel of information, Out of the CDC reported 300,000 cases documented each year, 1/3 of those affected develop neurological symptoms. Of those neurological cases, many progress to significant psychiatric syndromes. Despite the research and published reporting, few studies connect Lyme as a culprit of the pediatric neuro-inflammatory response known as PANS (pediatric acute-onset neuropsychiatric syndrome).

A common response when I mention the possibility of PANS as an underlying syndrome is " Lyme can cause PANS? I thought that only Strep did that."

Originally the acronym PANDAS was coined by Dr. Susan Swedo as a clinical description of a cluster of cases affecting children after a strep infection that triggered acute onset OCD, tic disorders, anxiety, Sydenham's chorea and other neuropsychiatric symptoms that prior to the strep infection didn't exist. In 2012 Dr. Swedo expanded PANDAS to PANS (pediatric acute-onset neuropsychiatric syndrome) which involved all infectious, environmental and possibly genetic triggers that could create an immune dysregulation as a response to inflammation on a child's brain. The PANDAS network website has a nice overview of both PANDAS and PANS.

When faced with treating a child for Lyme induced PANS, considering all potential underlying contributors is key to healing. Usually a number of insults have occurred that triggered PANS. Genetic SNPS, allergies, gut dysbiosis, viruses and other bacterial infections can all contribute. It's a stacking event with an eventual immune tipping. Antibiotic combinations with herbals/homeopathy to tackle the infection along with supplements and dietary restrictions to decrease the inflammation and support the immune system will provide relief.  Reoccurrence does and most likely will happen but is treatable. 

As providers, collectively, we don't communicate as effectively as we could with each other to form a strong integrative consensus regarding the neurological/cognitive involvement of Lyme disease in children. The current symptoms described by the CDC and local health departments regarding Lyme Disease is just the beginning. As parents, asking your primary care providers for Lyme and other tick-borne infection testing is a good first step.