Lyme & Autoimmunity

Is Chronic Lyme Disease an Autoimmune Disease?

Lyme Disease is a persistent bacterial infection that people and other mammals such as dogs can get through a bite of a tick. There is also research that shows that you can get Lyme Disease also from a mosquito bite. Amongst the research community there is also speculations that the Lyme infection may also be sexually transmitted or passed from a mother to a child, but more studies are needed.

When the tick bites you, it feeds on your blood and transmits the Lyme Disease bacteria called Borrelia Burgdorferi. Not all ticks will have the bacteria and scientists are also discovering different types of the Borrelia bacteria such as Borrelia Garinii.

If you have Lyme Disease you can have over 40 symptoms such as: migrating joint and muscle pain, joint swelling, brain fog, muscle twitching, depression, swollen glands, mood swings, hearing loss/tinnitus, upset stomach, shortness of breath, headaches, neck stiffness, facial paralysis (Bell’s Palsy), blurry/double vision, tremors, disorientation, disrupted sleep, heart palpitations/endocarditis, multiple chemical sensitivities (MCAS) and many, many more.

I didn’t know much about Lyme Disease until I got Neuroborreliosis myself, a more serious case of Lyme Disease, where the bacteria affect the central nervous system. This took me on a long journey of false negative tests, incredulous doctors (here, in the UK) and ultimately lead me to undergo a hyperthermia treatment in a private clinic in Germany.

Then, once the bacteria were eradicated through hyperthermia and numerous IV antibiotics I had to apply numerous nutritional and immune modulating protocols to recover. Along the way, I started asking a question that no one seemed to be asking – could the Lyme Disease bacteria trigger an autoimmune reaction in the body, so some of the symptoms in chronic Lyme are not caused by the bacteria infection itself, but by the ‘misguided’ immune system? I already had pre-existing autoimmune diseases, which perhaps explained why I got so unwell very quickly, and even after the Germany treatments, some of my symptoms persevered.

When I started looking into the research I was doing for my upcoming book ‘Lyme in the Limelight’, the published, peer reviewed studies, I was astounded! I was already aware how bacterial infections such as H.Pilory and Klebsiella may trigger autoimmune disease, in fact I have written an article about it you can access here, but why no one has ever thought that the Borrelia Bacteria, where not initially eradicated (which is often the case because of the issues with false negative testing and  difficult diagnosis), can over time trigger the immune system to attack self-tissue? Once autoimmunity is started it cannot be stopped, you cannot ‘cure yourself’ of an autoimmune disease, however, you may be able to manage it to a level where the symptoms are very minimal.

Here are the scientific mechanisms behind it:

Borrelia Burgdorferi and Molecular Mimicry

A common mechanism of action in most of these diseases is a process called ‘molecular mimicry’ – where the sequence similarities between foreign and self-proteins result in the cross-activation of autoreactive T or B cells of the immune system. In more simple words – your immune system loses the ability to recognise ‘self’ (friend) from ‘non-self’ (foe).

One way through which ‘bad’ bacteria can make us sick is the toxins they launch from their membranes called Lipopolysaccharides (LPS). In extreme cases, high levels of these toxins can cause dangerous conditions such as endotoxemia and sepsis. The Borrelia Burgdorferi bacteria does not have such toxins. Instead, on the outer surface of their cell, it has lipoproteins.

These lipoproteins in the Borrelia bacteria play important role in a wide variety of bacterial physiological processes – infection of different hosts (ticks, animals and humans), virulence of the infection and induction of immune reactions and inflammation. For example, Borrelia lipoproteins A and B bind to decorin on collagen fibres in the body, which may explain why the joints, nervous system and heart are affected in many people with Lyme Disease. Generally speaking, lipoproteins are usually found in the most resistant bacterial infections such as Mycobacterium tuberculosis (causing Tuberculosis), Streptococcus pneumoniae (causing Pneumonia), and Neisseria meningitidis (causing Meningitis and other forms of meningococcal disease such as Meningococcemia) and of course Borrelia burgdorferi causing Lyme Disease.

These bacteria, which possess lipoproteins on their cell surface do not have just one ‘trick up their sleeve’, they can launch numerous ‘lethal’ and strategic attacks depending on their environment. The Borrelia bacteria has been found to have at least 120 of these proteins (1)!

Animal research has suggested that Lyme Carditis, a known Lyme Disease complication, is caused by an autoimmune reaction via a molecular mimicry mechanism (2). The OspA protein, one of the many Borrelia lipoproteins expressed on the bacteria’s outer wall, cross reacts with myosin, one of the components of the cardiac (heart) muscle. The autoimmune reaction via molecular mimicry in Lyme Arthritis is very well established too, supported by numerous studies (3), (4), (5). The culprit in these cases is again the OspA protein, which appears to have a similar structure to the Lymphocyte function-associated antigen 1 (LFA-1) at T cell level (cells of the immune system).

The molecular mimicry mechanism seems to be also implicated in neurological manifestations of Lyme and also more severe cases of the disease called Lyme Neuroborreliosis (LNB), which has been detected in 20-30% of the total cases. When the disease progresses to this stage it is usually affecting both the central and peripheral nervous system and the manifestations can be very serious and life threatening such as such as meningitis (inflammation of the lining around the brain), poly radiculitis (peripheral nerves disorder), cranial neuritis (inflammation of the nerves in the brain stem), and encephalomyelitis (inflammation of the brain).

In fact, one of the earliest studies on molecular mimicry and Lyme that I came across from 1989 (6) revealed that the 41 kDa flagella protein (the flagella is like the ‘tail’ in some bacteria, which the Borrelia bacteria possesses too) cross reacts with the myelinated fibres of human peripheral nerve,  nerve cells and axons (a nerve fibre of the nervous system, which conducts electrical impulses) of the central nervous system, causing an auto-immune reaction. These findings were also more recently confirmed in a human study, too (7).

Furthermore, more targeted research (8) on the effects of the Borrelia bacteria on the nervous system reveals that the molecular mimicry mechanism also affects the crucial central nervous system cells. The degeneration of the axon cells of the nervous system is also linked to serious neurodegenerative diseases such as Parkinson’s, Alzheimer’s and even Amyotrophic Lateral Sclerosis (ALS). Indeed, there have been case reports of Lyme-associated Parkinsonism (9) and even a more recent case report (2020) of Neuroborreliosis associated ALS (10).

Have I convinced you yet that the physiological process of molecular mimicry is highly implicated in Lyme Disease mediated autoimmunity? I hope so, even the only ‘viable’ Lyme Disease vaccine, brought to the market in the late 1990s, was withdrawn because of molecular mimicry and autoimmunity concerns (11)!

Lyme Disease also affects the nervous system through other mechanisms, which are not necessarily molecular mimicry related. Lyme Disease has also been found to affect the microglial cells of the brain and spinal cord. These cells are a type of neuroglia and they act as the brain’s immune defence, accounting for 10-15% of the total cells in the brain. You can think of them as the brain’s immune system. Research (12) has suggested that these cells, when co-cultured with the Borrelia bacteria express a number of pro-inflammatory cytokines (inflammatory ‘messengers’) and in the presence of another nervous system cells called the SH-SY5Y (SY) neuroblastoma cells, this can also lead to neuronal ‘apoptosis’ – programmed death of important brain cells.

Further in vitro tests or lab tests suggests that the spirochetes of the Lyme bacteria can damage nervous cells (more specifically C6 glioma and PC-12 pheochromocytoma cells) of the nervous system (13). The damage can be done to both the central (brain and spinal cord) and the peripheral (all the nerves outside of the brain and spinal cord), the latter was evidenced by animal research, which showed that the Borrelia Burgdorferi bacteria can damage an area of the brain called the Dorsal Root Ganglia, which is responsible for carrying out messages between the peripheral and central nervous system (14).

The other known mechanism though which Lyme is linked to autoimmunity is through the activation of the Toll Like Receptors (TLRs). These play a key role in both innate and adaptive immune responses, our first and second defences against bacteria and pathogens as explained above. When TLRs are activated, these trigger pro-inflammatory genes, which usually help resolve an infection, however, if something is triggering these constantly, this might also lead to an overactive immune system and autoimmunity.

Some of the lipoproteins produced by the Lyme bacteria I mentioned earlier, but this time the OspC and the  Flagellin proteins (the proteins from the bacterial tail), have been known to activate specific TLR such as TLR2 and TLR5, which in turn affect immune system structures called Matrix Metalloproteinases (15), major group of enzymes that regulate cell-matrix composition and affect our immune system.

The regulation of these is also linked with autoimmune conditions such as Lupus, Sjogren’s Syndrome, Systemic Sclerosis, Rheumatoid Arthritis, Multiple Sclerosis, Polymyositis and Atherosclerosis (16). Borrelia Burgdorferi infection has also been linked to the activation of other TLRs such as TLR1 and TLR2 (17).

Lyme Disease Co-Infections and Autoimmunity

My research also found that Borrelia has the potential to trigger autoimmunity and this may be further exacerbated by the potential of common Lyme Disease co-infections to also trigger autoimmune disease, too. Babesia is a Malaria like parasite, which usually ‘comes’ with Lyme. It lives in the red blood cells and empties them in the process, leaving infected people severely anaemic. research (18) suggests that this parasitic infection may be associated with Autoimmune Haemolytic Anaemia.

The link between Mycoplasma, yet another bacterial co-infection, and autoimmunity is a bit more well established. A large cohort study with 116,084 patients found that having Mycoplasma infection is a major independent risk for developing an autoimmune condition called Ankylosing Spondylitis (19). The same ‘trigger’ connection was also observed in Juvenile Idiopathic Arthritis (20) and severe Haemolytic Anaemia (21).

Bartonella, also known as Cat Scratch Disease, one of the more common Lyme co-infections, has been known to mimic an autoimmune disease (22) in a young patient. Another case report of an adult (23) reveals how the infection mimicked another very little understood autoimmune disease called Adult Onset Still Disease.

More on this subject as well as a clear immune modulating protocol, which can be applied in cases where chronic Lyme Disease may be triggering autoimmunity, will be included in my upcoming book ‘Lyme in the Limelight’.

References:

1. Kovacs-Simon A, Titball RW, Michell SL. Lipoproteins of bacterial pathogens. Infection and Immunity. 2011.
2. Raveche ES, Schutzer SE, Fernandes H, Bateman H, McCarthy BA, Nickell SP, et al. Evidence of Borrelia autoimmunity-induced component of lyme carditis and arthritis. J Clin Microbiol. 2005;
3. Trollmo C, Meyer AL, Steere AC, Hafler DA, Huber BT. Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1α L Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells . J Immunol. 2001;
4. Steere AC, Glickstein L. Elucidation of Lyme arthritis. Nature Reviews Immunology. 2004.
5. Akin E, Aversa J, Steere AC. Expression of adhesion molecules in synovia of patients with treatment-resistant lyme arthritis. Infect Immun. 2001;
6. Aberer E, Brunner C, Suchanek G, Klade H, Barbour A, Stanek G, et al. Molecular mimicry and lyme borreliosis: A shared antigenic determinant between Borrelia burgdorferi and human tissue. Ann Neurol. 1989;
7. Kuenzle S, Von Büdingen HC, Meier M, Harrer MD, Urich E, Becher B, et al. Pathogen specificity and autoimmunity are distinct features of antigen-driven immune responses in neuroborreliosis. Infect Immun. 2007;
8. Sigal LH. Cross-Reactivity between Borrelia burgdorferi Flagellin and a Human Axonal 64,000 Molecular Weight Protein. J Infect Dis. 1993;
9. Cassarino DS, Quezado MM, Ghatak NR, Duray PH. Lyme-associated parkinsonism: A neuropathologic case study and review of the literature. In: Archives of Pathology and Laboratory Medicine. 2003.
10. Wirsching I, Ort N, Üçeyler N. ALS or ALS mimic by neuroborreliosis—A case report. Clin Case Reports. 2020;
11. Poland GA. Vaccines against lyme disease: What happened and what lessons can we learn? Clin Infect Dis. 2011;
12. Myers TA, Kaushal D, Philipp MT. Microglia are mediators of Borrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells. PLoS Pathog. 2009;
13. Peters DJ, Benach JL. Borrelia burgdorferi adherence and injury to undifferentiated and differentiated neural cells in vitro. J Infect Dis. 1997;
14. Ramesh G, Santana-Gould L, Inglis FM, England JD, Philipp MT. The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia. J Neuroinflammation. 2013;
15. Bernard Q, Thakur M, Smith AA, Kitsou C, Yang X, Pal U. Borrelia burgdorferi protein interactions critical for microbial persistence in mammals. Cellular Microbiology. 2019.
16. Ram M, Sherer Y, Shoenfeld Y. Matrix metalloproteinase-9 and autoimmune diseases. Journal of Clinical Immunology. 2006.
17. Rahman S, Shering M, Ogden NH, Lindsay R, Badawi A. Toll-like receptor cascade and gene polymorphism in host-pathogen interaction in Lyme disease. Journal of Inflammation Research. 2016.
18. Narurkar R, Mamorska-Dyga A, Nelson JC, Liu D. Autoimmune hemolytic anemia associated with babesiosis. Biomark Res. 2017
19. Chu KA, Chen W, Hung YM, Wei JCC. Increased risk of ankylosing spondylitis after Mycoplasma pneumonia: A Nationwide population-based study. Med (United States). 2019;
20. Postepski J, Opoka-Winiarska V, Kozioł-Montewka M, Korobowicz A, Tuszkiewicz-Misztal E. Role of mycoplasma pneumoniae infection in aetiopathogenesis of juvenile idiopatic arthritis. Med Wieku Rozwoj. 2003;
21. Khan FY, Yassin MA. Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia: Case report and literature review. Brazilian J Infect Dis. 2009;
22. Maritsi DN, Zarganis D, Metaxa Z, Papaioannou G, Vartzelis G. Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease . Case Rep Pediatr. 2013;
23. Durey A, Kwon HY, Im JH, Lee SM, Baek JH, Han SB, et al. Bartonella henselae infection presenting with a picture of adult-onset Still’s disease. Int J Infect Dis. 2016;