Persistent Borrelia burgdorferi protein antigen in CD16⁺ monocytes is associated with monocyte-skewed immune dysregulation in post-treatment Lyme disease syndrome (PTLDS)

The mechanisms underlying these symptoms remain incompletely understood and have been attributed to ongoing low-level infection, autoimmunity, or immune dysregulation driven by residual bacterial antigens. We investigated whether Borrelia burgdorferi protein antigen persists in long-lived monocyte subsets in PTLDS patients and is associated with broader immune dysregulation.

CD14⁺CD16⁺ monocytes from 10 patients with PTLDS were analyzed by mass spectrometry; plasma from all 10 was profiled on a 14-plex cytokine panel against 50 healthy donors; PBMCs from 6 patients (3 antigen-positive and 3 antigen-negative) underwent RT-qPCR and bulk RNA-seq with immune-compartment profiling. FlaB and OspC were detected in CD14⁺CD16⁺ monocytes months to years after treatment, whereas Borrelia burgdorferi transcript was not detected.