What’s new: advances in serodiagnostic testing, role of T cell activation in Lyme arthritis, and post-treatment Lyme disease syndrome.
References1. Branda JA, Body BA, Boyle J, et al. Advances in serodiagnostic testing for Lyme disease are at hand. Clin Infect Dis. 2018;66:1133-1139. doi: 10.1093/cid/cix943.2. Whiteside SK, Snook JP, Ma Y, et al. IL-10 deficiency reveals a role for TLR2-dependent bystander activation of T cells in Lyme arthritis. J Immunol. 2018;200:1457-1470. doi: 10.4049/jimmunol.1701248.3. Rebman AW, Bechtold KT, Yang T, et al. The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with posttreatment Lyme disease syndrome. Front Med (Lausanne). 2017;4:224. doi: 10.3389/fmed.2017.00224.
Highlights of 3 studies in Lyme arthritis include: (1) advances in serodiagnostic testing for Lyme disease may identify the infection before chronic health problems, such as Lyme arthritis, appear; (2) cascading inflammation associated with Lyme arthritis has been linked to an overactive immune response; and (3) severe symptoms linger in some patients after antibiotic treatment.1-3 Scroll through the slides for the latest findings and their clinical implications.
(Vials: ©Africa Studio/Shutterstock.com; tick: ©South 12th Photography/Shutterstock.com; knees: ©Stasique/Shutterstock.com.)
The only FDA-approved Lyme disease tests are based on technology developed more than 2 decades ago. The current standard relies on detecting antibodies produced by the immune system in response to the disease.
However, many people produce similar, cross-reactive antibodies in response to other bacteria not associated with Lyme disease, which causes confusing results and makes test accuracy more difficult.1
Clinical Implications: Updated methods would help physicians decide when to prescribe antibiotics to clear the infection and help avoid severe long-term health problems.
“New tests are at hand that offer more accurate, less ambiguous test results that can yield actionable results in a timely fashion. Improved tests will allow for earlier diagnosis, which should improve patient outcomes,” said senior author Steven Schutzer, MD, of Rutgers New Jersey Medical School. “New tests are more exact and are not as susceptible to the same false-positive or false-negative results associated with current tests.”
A receptor on T cells interacts with molecules on the surface of the Borrelia burgdorferi, the bacterium transferred during a tick bite, which results in bystander activation. This activation mechanism triggers the T cell to produce inflammatory molecules that accumulate around the joints and contribute to inflammation and arthritis.
A mouse model of persistent Lyme arthritis showed some of the newly activated T cells can interact with residual bacteria that persist long after the initial tick bite, producing a cascading cycle of inflammation that could lead to infection-induced autoimmunity.2
Clinical Implications: The results suggest new therapeutic approaches, such as those that focus on anti-inflammatory mechanisms, might be more effective for patients with persistent Lyme arthritis.
“Through bystander activation, a whole repertoire of T cells may be activated, independent of their specificity for infecting pathogens. If you can suppress T cell activation for the short term, we might help re-establish the control mechanism for the immune response in the body,” said senior author Janis Weis, PhD, professor of pathology at the University of Utah Health.
A case series of 61 patients with well-documented post-treatment Lyme disease syndrome (PTLDS) was compared with 26 healthy controls who had neither a clinical history of Lyme disease nor current antibodies to Borrelia burgdorferi. All participants had a physical examination, clinical laboratory testing, standardized questionnaires, and a 36-item current symptom list.3
Those with PTLDS reported significantly greater fatigue, pain, sleep disturbance, and depression as compared with controls. The physical examination and clinical laboratory tests showed few objective abnormalities.
Clinical Implications: The standardized symptom questionnaires reveal that patients with PTLDS are highly, clinically significantly symptomatic, with poor health-related quality of life.
“Even though their exams and lab tests didn’t show much in the way of a common or clear biological marker or markers of PTLDS, it’s clear these patients don’t feel well. These symptoms are more severe than what the average non-PTLDS patient is experiencing even on a bad day,” said co-author Kathleen Bechtold, PhD, associate professor of physical medicine and rehabilitation at the Johns Hopkins University School of Medicine. A systematic approach to diagnosis and symptom measurement can successfully identify patients with PTLDS, she said.