Causes of Long-Term Lyme Disease Symptoms
Long-term Lyme disease symptoms are all too common. In one follow-up study, “36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties” six months after their initial infection. 3
Persistent Lyme disease symptoms may arise from several mechanisms, including immune dysregulation, inflammation, coinfections, and microbial survival strategies such as antigenic variation.
So how could Lyme disease symptoms persist long term?
Recent research suggests that antigenic variation may allow the Lyme bacterium to evade the immune system and survive for extended periods.
[bctt tweet=”Antigenic variation may explain why some Lyme disease patients experience persistent symptoms.” username=”DrDanielCameron”]
In their article “Changing of the guard: How the Lyme disease spirochete subverts the host immune response,” Chaconas and colleagues explain how antigens—proteins found on the surface of the spirochetal bacteria—play a sort of “cat-and-mouse” game with the immune system. 4
Other pathogens use antigenic variation
Antigenic variation is not unique to Lyme disease, Chaconas writes. Rather, it is a “common pathogenic ruse employed by several bacterial, protozoan, and fungal pathogens.”
Many bacterial and protozoal pathogens continually alter their surface antigens as a way of evading the immune system.
In these organisms, surface proteins change repeatedly, allowing the microbes to escape recognition by antibodies and immune cells.
The immune system is designed to recognize these antigens and destroy invading organisms. But when the pathogen changes these surface proteins, the immune response may no longer recognize the bacteria.
“This process involves changes in a prominent surface antigen such that it is no longer recognized by the host acquired immune response,” Chaconas writes. 4
Altering the immune response
By changing the antigens, the Lyme spirochete may gain time to survive within the host.
This process may help explain why Lyme disease symptoms continue long term in some individuals.
As the authors explain, “By the time the host has assembled and produced antibodies to clear an infecting organism, new variants have appeared, which fly under the radar in terms of immune surveillance.” 4
The process is like a cat-and-mouse game, which can continue for the long haul, allowing pathogenic organisms to evade immune clearance and potentially persist within the host.
Spirochetes buy even more time by changing their antigens yet again.
“By the time a new generation of antibody molecules has been fashioned to clear the variant pathogens, yet another collection of organisms with prominent but unrecognizable surface antigens has appeared,” the authors write. 4
Vls gene responsible for antigenic variation
The gene vls locus plays an important role in antigenic variation.
“The vls system is required for long-term survival of Lyme Borrelia in infected mammals and represents an important mechanism of immune evasion,” writes Norris in Microbiology Spectrum. 5
“The vls locus is akin to a perpetual motion machine for antigenic variation in Lyme Borrelia species,” Norris explains. 5
Implications for persistent Lyme disease symptoms
Understanding how Lyme bacteria evade the immune system may help explain why some patients experience ongoing symptoms after infection.
Further studies examining the vls locus may provide insight into whether therapies that block recombinational switching could interfere with immune evasion.
If such therapies were developed, they might provide a strategy to target drug-surviving spirochetes and reduce the risk of long-term persistence.
These mechanisms are part of the broader clinical challenge discussed in persistent Lyme disease and post-treatment Lyme disease syndrome, where symptoms may reflect a complex interaction between infection, immune response, and inflammation.
Related Articles:
Persistent Lyme infection or inflammatory immune response?
References:
- Shadick NA, Phillips CB, Logigian EL, et al. The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. Ann Intern Med. 1994;121(8):560-567.
- Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol. 1994;21(3):454-461.
- Aucott JN, Rebman AW, Crowder LA, Kortte KB. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Qual Life Res. 2013;22(1):75-84.
- Chaconas G, Castellanos M, Verhey TB. Changing of the guard: How the Lyme disease spirochete subverts the host immune response. J Biol Chem. 2020 Jan 10;295(2):301-313.
- Norris SJ. vls Antigenic Variation Systems of Lyme Disease Borrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity. Microbiol Spectr. 2014 Dec;2(6).
Hello, I began reading your blog a few months and have learned a lot. My interest is because I have untreated chronic Lyme. I believe I contracted Lyme as soon as I moved back to upstate new york. In late 2015 I had what I call “my initial attack” , where I thought I was going to die.although I was an avid fisherman, rock climber and repeller, the doctors had everything wrong. They tested me for everything except Lyme, this even included a left leg muscle biopsy, neurologic problems which led my neurologist stated that in her opinion, I’ve had numerous Lyme infections, Lyme meningitis and Lyme carditis . Long story semi short, I go through horrible flareups and suffer from advanced arthritis, chest pains, left leg is week and unstable and much more. How, and where, could I see a Lyme specialist?
Call the office at 914 666 4665. You could also contact Global Lyme Alliance or Lyme disease association for names.
I seriously cannot find ANY doctors in the Pittsburgh area who believe in this. We have great doctors! I have been sick since 1990. They diagnosed it as CFS. I didn’t have a rash, just symptoms. In 2016, Infectious Disease said that I most likely had it at once point. At that point, the test had just one reactive marker. I would love to not get shocked anymore….
I have had to use clinical judgement when there is only one band. There must have been something the ID was looking at. There is no test to be sure Lyme disease had resolved.
I had a long-time, undiagnosed bout with Lyme (about 2 years) before finally showing up in bloodwork. Another 2+ years of antibiotics which did not knock down my infection until I had a Pic-line installed in my arm which enabled me to self-inject liquid antibiotics directly into my heart. I developed congestive heart failure, had 2 sets of stents (4 total) inserted in my coronary arteries, and finally underwent an aortic valve replacement in 2019. I continue to suffer from severe muscle spasms in legs and arms, sporadic crippling spasms in my hands and feet, and recurring bouts of “Tickling Itching” in my extremities which is un-relentless & debilitating usually lasting 3 to 5 days before subsiding. Blood test results have indicated that the presence of Lyme falls short of the State mandated benchmark for treatment. I am a Type 2 Diabetic, have had by-pass surgery and suffer from neck issues.
I find it a challenge when my patient has more than one condition. I have to address each condition concurrently.