CCL19 as a Chemokine Risk Factor for Post-Treatment Lyme Disease Syndrome: A Prospective Clinical Cohort Study.
Aucott JN1,
Soloski MJ2,
Rebman AW2,
Crowder LA3,
Lahey LJ4,
Wagner CA4,
Robinson WH4,
Bechtold KT5.
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Abstract
Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed post-treatment Lyme disease syndrome (PTLDS). The objective of this study is to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as Return to Health, Symptoms Only, and PTLDS. Significance analysis of microarrays identified 7 of the 64 immune mediators as differentially regulated by group. Generalized logit regressions controlling for potential confounders identified post-treatment levels of the T-cell chemokine CCL19 as independently associated with clinical outcome group. ROC analysis identified a CCL19 cutoff of > 111.67 pg/mL at one month following treatment completion as 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the post-treatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.
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