title: CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study.
abstract: Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was 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 the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 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 posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Lutherville, Maryland, USA jaucott2@jhmi.edu.
authors.forename: John N
authors.initials: JN
authors.lastname: Aucott
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Lutherville, Maryland, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Soloski
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Lutherville, Maryland, USA.
authors.forename: Alison W
authors.initials: AW
authors.lastname: Rebman
authors.affiliation: Lyme Disease Research Foundation, Lutherville, Maryland, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Crowder
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA, and Veterans Affairs Palo Alto Health Care System CCSR, Palo Alto, California, USA.
authors.forename: Lauren J
authors.identifier: http://orcid.org/0000-0003-0026-6864
authors.initials: LJ
authors.lastname: Lahey
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA, and Veterans Affairs Palo Alto Health Care System CCSR, Palo Alto, California, USA.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA, and Veterans Affairs Palo Alto Health Care System CCSR, Palo Alto, California, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Kathleen T
authors.initials: KT
authors.lastname: Bechtold
mesh_terms: D000328:Adult; D000368:Aged; D054415:Chemokine CCL19 / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008193:Lyme Disease / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: C515460:CCL19 protein, human; D054415:Chemokine CCL19