Tick-Specific Borrelial Antigens Appear to Be Upregulated in American but Not European Patients With Lyme Arthritis, a Late Manifestation of Lyme Borreliosis

Li, Xin; Strle, Klemen; Wang, Peng; Acosta, David; McHugh, Gail; Sikand, Nikhil; Strle, Franc; Steere, Allen C.

doi:10.1093/infdis/jit269

Cited by 14 publications

(12 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the brain of two treated animals, rare morphologically intact spirochetes immunoreactive to OspA were observed in the heart of one treated animal (IK14). Increased OspA serum titers have been reported in American patients with Lyme arthritis and indicate differential gene expression of B. burgdorferi dependent on tissue localization 46, 47. Furthermore, experimental studies in mice have shown enhanced OspA expression in host-adapted spirochetes during inflammation 48 and ospA transcription was evident posttreatment in both murine studies and our prior study in macaques 13, 49.…”

Section: Discussionsupporting

confidence: 60%

Late Disseminated Lyme Disease

Crossland

Álvarez

Embers

2018

The American Journal of Pathology

View full text Add to dashboard Cite

Nonhuman primates currently serve as the best experimental model for Lyme disease because of their close genetic homology with humans and demonstration of all three phases of disease after infection with Borrelia burgdorferi. We investigated the pathology associated with late disseminated Lyme disease (12 to 13 months after tick inoculation) in doxycycline-treated (28 days; 5 mg/kg, oral, twice daily) and untreated rhesus macaques. Minimal to moderate lymphoplasmacytic inflammation, with a predilection for perivascular spaces and collagenous tissues, was observed in multiple tissues, including the cerebral leptomeninges, brainstem, peripheral nerves from both fore and hind limbs, stifle synovium and perisynovial adipose tissue, urinary bladder, skeletal muscle, myocardium, and visceral pericardium. Indirect immunofluorescence assays that combined monoclonal (outer surface protein A) and polyclonal antibodies were performed on all tissue sections that contained inflammation. Rare morphologically intact spirochetes were observed in the brains of two treated rhesus macaques, the heart of one treated rhesus macaque, and adjacent to a peripheral nerve of an untreated animal. Borrelia antigen staining of probable spirochete cross sections was also observed in heart, skeletal muscle, and near peripheral nerves of treated and untreated animals. These findings support the notion that chronic Lyme disease symptoms can be attributable to residual inflammation in and around tissues that harbor a low burden of persistent host-adapted spirochetes and/or residual antigen.

show abstract

Section: Discussionsupporting

confidence: 60%

Late Disseminated Lyme Disease

Crossland

Álvarez

Embers

2018

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…This proportion is similar to that documented in southwest Virginia, where 6% of healthy, non‐vaccinated horses were seropositive for OspA antibodies . The magnitude of OspA antibody response in American human patients with Lyme arthritis has been directly correlated with more severe and prolonged disease . In our study, more horses with positive CSF OspA results or positive CSF : serum OspA ratios had a final diagnosis of another neurologic disease than neuroborreliosis.…”

Section: Discussionsupporting

confidence: 87%

Cerebrospinal fluid Lyme multiplex assay results are not diagnostic in horses with neuroborreliosis

Johnson

Johnstone

Stefanovski

2018

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundThe accuracy of the Lyme multiplex assay for the diagnosis of neuroborreliosis in horses is unknown.Hypothesis/ObjectivesTo describe Lyme multiplex results in horses with a postmortem diagnosis of neuroborreliosis. The hypothesis was that paired serum and cerebrospinal fluid (CSF) results and a CSF : serum ratio would allow differentiation of horses with neuroborreliosis from those with other neurologic diseases.AnimalsNinety horses that had neurologic examinations, serum and CSF Lyme multiplex analyses, and postmortem examination of the nervous system performed.MethodsRetrospective study. Data collected included signalment, ante‐ and postmortem diagnoses, and serum and CSF Lyme multiplex results. The CSF : serum ratio was calculated by dividing CSF median fluorescent intensity (MFI) by serum MFI for each result.ResultsTen horses had a final diagnosis of neuroborreliosis, 70 were diagnosed with other neurologic diseases, and 10 had no neurologic disease. Not all horses with neuroborreliosis had positive results: 4/10 had at least 1 positive serum result, 5/10 had at least 1 positive CSF result, and 3/10 had at least 1 CSF result 4‐fold higher than the corresponding serum result. Results were similar for the 70 horses with other neurologic diseases: 53% had at least 1 positive serum result, 50% had at least 1 positive CSF result, and 16% had at least 1 CSF result 4‐fold higher than the corresponding serum result.Conclusions and Clinical ImportancePositive Lyme multiplex results were common in horses with neurologic diseases and did not adequately differentiate horses with neuroborreliosis from horses with other disorders.

show abstract

“…That we are seeing it induced after doxycycline treatment is of interest and may parallel what we see with OspA (below). OspD is an outer membrane protein, located on plasmid lp38, which is known to be antigenic (Li et al, 2013) and expressed more highly in ticks than in the mammalian host (Li et al, 2007). BBA62 was described in 1997 as a 6.6 kD lipoprotein that did not appear to induce antibodies by animals needle-inoculated with B. burgdorferi (Lahdenne et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, ospA, ospB , and ospD appear to be regulated by the stress-response regulator bosR (Wang et al, 2013). These gene products are possible markers of dormancy, given their expression in ticks and in late Lyme arthritis (Li et al, 2013). In our study, bosR was shown to be up-regulated 0.325-fold following treatment and rpoS was up 0.386-fold; however, the p -values indicate that these were not significant perturbations.…”

Section: Discussionmentioning

confidence: 99%

The Functional and Molecular Effects of Doxycycline Treatment on Borrelia burgdorferi Phenotype

et al. 2019

View full text Add to dashboard Cite

Recent studies have shown that Borrelia burgdorferi can form antibiotic-tolerant persisters in the presence of microbiostatic drugs such as doxycycline. Precisely how this occurs is yet unknown. Our goal was to examine gene transcription by B. burgdorferi following doxycycline treatment in an effort to identify both persister-associated genes and possible targets for antimicrobial intervention. To do so, we performed next-generation RNA sequencing on doxycycline-treated spirochetes and treated spirochetes following regrowth, comparing them to untreated B. burgdorferi . A number of genes were perturbed and most of those which were statistically significant were down-regulated in the treated versus the untreated or treated/re-grown. Genes upregulated in the treated B. burgdorferi included a number of Erp genes and rplU , a 50S ribosomal protein. Among those genes associated with post-treatment regrowth were bba74 (Oms28), bba03 , several peptide ABC transporters, ospA, ospB , ospC , dbpA and bba62 . Studies are underway to determine if these same genes are perturbed in B. burgdorferi treated with doxycycline in a host environment.

show abstract

Tick-Specific Borrelial Antigens Appear to Be Upregulated in American but Not European Patients With Lyme Arthritis, a Late Manifestation of Lyme Borreliosis

Cited by 14 publications

References 48 publications

Late Disseminated Lyme Disease

Late Disseminated Lyme Disease

Cerebrospinal fluid Lyme multiplex assay results are not diagnostic in horses with neuroborreliosis

The Functional and Molecular Effects of Doxycycline Treatment on Borrelia burgdorferi Phenotype

Contact Info

Product

Resources

About