An Enhanced ELISPOT Assay for Sensitive Detection of Antigen-Specific T Cell Responses to Borrelia burgdorferi

Abstract

Lyme Borreliosis is an infectious disease caused by the spirochete Borrelia burgdorferi that is transmitted through the bite of infected ticks. Both B cell-mediated humoral immunity and T cell immunity develop during natural Borrelia infection. However, compared with humoral immunity, the T cell response to Borrelia infection has not been well elucidated. In this study, a novel T cell-based assay was developed and validated for the sensitive detection of antigen-specific T cell response to B. burgdorferi. Using interferon-γ as a biomarker, we developed a new enzyme-linked immunospot method (iSpot LymeTM) to detect Borrelia antigen-specific effector/memory T cells that were activated in vivo by exposing them to recombinant Borrelia antigens ex vivo. To test this new method as a potential laboratory diagnostic tool, we performed a clinical study with a cohort of Borrelia positive patients and healthy controls. We demonstrated that the iSpot Lyme assay has a significantly higher specificity and sensitivity compared with the Western Blot assay that is currently used as a diagnostic measure. A comprehensive evaluation of the T cell response to Borrelia infection should, therefore, provide new insights into the pathogenesis, diagnosis, treatment and monitoring of Lyme disease.

Biomarker‐guided clinical development of the first‐in‐class anti‐inflammatory FPR2/ALX agonist ACT‐389949

“…Although TNF‐α and IL‐6 concentrations increased to levels measured under inflammatory conditions , no effect on body temperature and CRP could be demonstrated and general tolerability was good.…”

Current State of Tick-Borne Borreliosis (Lyme Disease) in Children

“…Однако диагностическая ценность этих мето-дов исследована недостаточно, и они не могут быть реко-мендованы для рутинной лабораторной диагностики [7,8,22,[29][30][31].…”

Prospective comparison of two enzyme-linked immunosorbent spot assays for the diagnosis of Lyme neuroborreliosis

“… or the enzym‐linked immunosorbent spot (ELISpot) assay (iSpot Lyme) described by Jin et al . . Most studies on cellular assays have used poorly described study populations and lack clinical validations.…”

“…Some of these assays are based on the proliferation of T cells, such as the lymphocyte transformation test (LTT) described by von Baehr et al [13] or the LTT-memory lymphocyte immunostimulation assay (MELISA) described by Valentine-Thon et al [14]. Other assays detect cytokines which are secreted by T cells upon stimulation with Borrelia antigens, such as the Quantiferon test described by Callister et al [15] or the enzym-linked immunosorbent spot (ELISpot) assay (iSpot Lyme) described by Jin et al [16]. Most studies on cellular assays have used poorly described study populations and lack clinical validations.…”