Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms

Chandra, Abhishek; Wormser, Gary P.; Klempner, Mark S.; Trevino, Richard P.; Crow, Mary K.; Latov, Norman; Alaedini, Armin

doi:10.1016/j.bbi.2010.03.002

Cited by 72 publications

(66 citation statements)

References 41 publications

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“…In the case of antibiotic-refractory late Lyme arthritis, the persistence of spirochetal antigens has also been hypothesized to lead to immune dysregulation in CD4 ϩ T-cell subsets (21). Lastly, PTLDS has been suggested to have an autoimmune component, and this is supported by the finding of antineural antibodies in one cohort of patients with PTLDS (22).…”

supporting

confidence: 64%

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Aucott

Soloski

Crowder³

et al. 2016

Clin Vaccine Immunol

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d 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.

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supporting

confidence: 64%

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Aucott

Soloski

Crowder³

et al. 2016

Clin Vaccine Immunol

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“…Table 1 shows patient group characteristics; see below for the assay procedure. The source of samples and selection criteria have been previously described in detail (6,16). Of the 54 specimens analyzed, 34 were from patients who had a history of single or multiple EM.…”

Section: Methodsmentioning

confidence: 99%

“…The original diagnosis of acute Lyme disease in these currently healthy subjects was confirmed by recovery of B. burgdorferi in cultures of skin and/or blood. The source of samples and selection criteria were previously described (6). Serum samples from 20 healthy subjects without history or serologic evidence of past or present Lyme disease (non-Lyme healthy group) were also included in the study.…”

Section: Methodsmentioning

confidence: 99%

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Anti-Borrelia burgdorferi Antibody Profile in Post-Lyme Disease Syndrome

Chandra

Wormser

Marques

et al. 2011

Clin. Vaccine Immunol.

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Patients with post-Lyme disease syndrome (PLDS) report persistent symptoms of pain, fatigue, and/or concentration and memory disturbances despite antibiotic treatment for Lyme borreliosis. The etiopathogenesis of these symptoms remains unknown and no effective therapies have been identified. We sought to examine the antiborrelia antibody profile in affected patients with the aim of finding clues to the mechanism of the syndrome and its relationship to the original spirochetal infection. Serum specimens from 54 borreliaseropositive PLDS patients were examined for antibodies to Borrelia burgdorferi proteins p18, p25, p28, p30, p31, p34, p39, p41, p45, p58, p66, p93, and VlsE by automated immunoblotting and software-assisted band analysis. The presence of serum antibodies to the 31-kDa band was further investigated by examination of reactivity against purified recombinant OspA protein. Control specimens included sera from 14 borreliaseropositive individuals with a history of early localized or disseminated Lyme disease who were symptom free (post-Lyme healthy group), as well as 20 healthy individuals without serologic evidence or history of Lyme disease. In comparison to the post-Lyme healthy group, higher frequencies of antibodies to p28 (P < 0.05), p30 (P < 0.05), p31 (P < 0.0001), and p34 (P < 0.05) proteins were found in the PLDS group. Assessment of antibody reactivity to recombinant OspA confirmed the presence of elevated levels in PLDS patients (P < 0.005). The described antiborrelia antibody profile in PLDS offers clues about the course of the antecedent infection in affected patients, which may be useful for understanding the pathogenic mechanism of the disease.

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“…The source of samples and case definition of PTLDS have been previously described [11,14,15]. Patients had at least 1 of the following: a history of EM skin lesion, early neurologic or cardiac symptoms attributed to Lyme disease, late neurologic manifestations, or Lyme arthritis.…”

Section: Patients and Controlsmentioning

confidence: 99%

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease

Uhde

Ajamian

et al. 2016

Clin Infect Dis.

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Background. Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.Methods. Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.Results. CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibioticrefractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.Conclusions. These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection.

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Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms

Cited by 72 publications

References 41 publications

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Anti-Borrelia burgdorferi Antibody Profile in Post-Lyme Disease Syndrome

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease

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