Biologic Markers of Antibiotic-Refractory Lyme Arthritis in Human: A Systematic Review

Abstract

Abstract Introduction Lyme disease—also known as Lyme borreliosis (LB)—is the most common vector-borne disease in North America and Europe. It may result in substantial morbidity, primarily from persistent Lyme arthritis (LA) that—although treatable—can develop into antibiotic-refractory LA (A-RLA). The aim of this study is to systematically review and evaluate a range of biomarkers for their potential predictive value in the development of A-RLA. Methods We conducted a systematic review of studies examining biomarkers among patients with A-RLA from MEDLINE via OVID, EMBASE and Web of Science databases and identified a total of 26 studies for qualitative analysis. Results All studies were of patient populations from the USA, with the exception of one from Europe. We identified an array of biomarkers that are commonly modulated in the A-RLA compared with subjects with antibiotic-responsive LA. These included a range of inflammatory markers (IL-6, IL-8, IL-10, IL-1β, IL-23, IL-17F, TNFα, IFNγ, CXCL9, CXCL10, CCL2, CCL3 and CCL4, CRP), factors along the innate and adaptive immune response pathways (e.g., CD4+ T cells, GITR receptors, OX40 receptors, IL-4+CD4+Th2 cells, IL-17+CD4+ T cells) and an array of miRNA species (e.g., miR-142, miR-17, miR-20a, let-7c and miR-30fam). Conclusion The evidence base of biologic markers for A-RLA is limited. However, a range of promising biomarkers have been identified. Cytokines and chemokines related to Th17 pathway together with a number of miRNAs species (miR-146a, miR-155 and let-7a) may be promising candidates in the prediction of A-RLA. A panel of multiple biomarkers may yield clinically relevant prediction of the possible resistance at the time of LA first diagnosis. Funding Public Health Agency of Canada.

Keywords

• Antibiotic-refractory Lyme arthritis
• Biomarkers
• Human
• Inflammation
• Systematic review