After treatment for acute Lyme disease, approximately 15-20% of people suffer from pain, fatigue and brain fog which is severe enough to impair their ability to function with daily activities. Little is known, however, about which individuals are at greatest risk for this potentially debilitating condition. In the research world, a research definition known as Post Treatment Lyme Disease (PTLD) is used to study this condition. Patients with PTLD experience persistent symptoms and quality of life impairment for 6 months or longer following standard of care antibiotic treatment. Identifying risk factors for PTLD could enable the development of biomarker diagnostics and earlier, targeted, and potentially preventative therapy in patients at highest risk.
Immune dysfunction is thought to be one of the major risks for PTLD development. In addition to providing diagnostic information, autoantibodies can provide insight into mechanisms of immune activation. However, autoantibodies have not been well-studied in PTLD. A recent publication by the Johns Hopkins Lyme Disease Research Center, found that currently recognized autoantibodies typically associated with rheumatic disease (e.g., lupus, myositis and scleroderma) were not more prevalent in patients with Lyme disease, though these results did not exclude the possible predictive value of new, yet to be described, autoantibodies.
Annexin A2 (AnxA2) antibodies have been previously identified in Lyme arthritis and were shown to associate with immune dysfunction. However, these antibodies had not yet been described in post treatment Lyme disease. A recent study published by the Johns Hopkins Research Center investigated whether these AnxA2 autoantibodies could help predict someone’s risk for PTLD. Results showed that compared to patients who returned to health after Lyme disease, a higher proportion of patients with PTLD made AnxA2 antibodies. AnxA2 antibody levels decreased for patients with complete clinical recovery, whereas these antibodies often remained elevated in patients with PTLD and could even persist for several years.
AnxA2 antibodies are thought to cause platelet activation and endothelial dysfunction. Interestingly, the damages caused by endothelial dysfunction are thought to possibly contribute to dysautonomia and neurocognitive deficits, both of which are prevalent in PTLD as well as other infection-associated chronic illnesses such as long COVID. PTLD and long COVID have symptom overlaps and endothelial dysfunction is one possible mechanism overlap that could potentially be targeted by therapeutics.
More research is needed to determine if AnxA2 autoantibodies might be a key predictive autoantibody signature for PTLD.
Contemporarily, a predictive autoantibody signature was recently identified for multiple sclerosis, another infection-associated chronic illness. A distinct autoantibody pattern was found in 10% of MS patients many years prior to illness. The binding pattern is similar to common pathogens, such as the Epstein-Barr Virus, that has previously been associated with MS. The immune system may aberrantly be mistaking human protein from pathogen, setting up a chronic neuro-immune condition.
By better understanding autoimmune activations and patterns, biomarker diagnostics and targeted treatments can potentially be developed to help cure these chronic infection-associated diseases.
