T H 17 Cytokine Responses in Lyme Disease Correlate with Borreliaburgdorferi Antibodies During Early Infection in Patients with Erythema Migrans and with Autoantibodies Late in the Illness in Patients with Antibiotic-Refractory Lyme Arthritis

ABSTRACTCurrent serodiagnostic assays for Lyme disease are inadequate at detecting early infection due to poor sensitivity and nonspecificity that arise from the use of whole bacteria or bacterial proteins as assay targets; both targets contain epitopes that are cross-reactive with epitopes found in antigens of other bacterial species. Tests utilizing peptides that contain individual epitopes highly specific forBorrelia burgdorferias diagnostic targets are an attractive alternative to current assays. Using an overlapping peptide library, we mapped linear epitopes in OspC, a critical virulence factor ofB. burgdorferirequired for mammalian infection, and confirmed the results by enzyme-linked immunosorbent assay (ELISA). We identified a highly conserved 20-amino-acid peptide epitope, OspC1. Via ELISA, OspC1 detected specific IgM and/or IgG in 60 of 98 serum samples (62.1%) obtained from patients with erythema migrans (early Lyme disease) at the time of their initial presentation. By comparison, the commercially available OspC peptide PepC10 detected antibody in only 48 of 98 serum samples (49.0%). In addition, OspC1 generated fewer false-positive results among negative healthy and diseased (rheumatoid arthritis and positive Rapid Plasma Reagin [RPR+] test result) control populations than did PepC10. Both highly specific and more sensitive than currently available OspC peptides, OspC1 could have value as a component of a multipeptide Lyme disease serological assay with significantly improved capabilities for the diagnosis of early infection.

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Seasonality of Acute Lyme Disease in Children

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6040196 ◽

2021 ◽

Vol 6 (4) ◽

pp. 196

Author(s):

Kathryn M. Sundheim ◽

Michael N. Levas ◽

Fran Balamuth ◽

Amy D. Thompson ◽

Desiree N. Neville ◽

...

Keyword(s):

Lyme Disease ◽

Regression Models ◽

Disease Incidence ◽

Erythema Migrans ◽

The United States ◽

Lyme Arthritis ◽

Cranial Neuropathy ◽

Acute Arthritis ◽

Presenting Symptoms ◽

Fourier Regression

Due to the life cycle of its vector, Lyme disease has known seasonal variation. However, investigations focused on children have been limited. Our objective was to evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States. We enrolled children presenting to one of eight Pedi Lyme Net participating emergency departments. Cases were classified based on presenting symptoms: early (single erythema migrans (EM) lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis). We defined a case of Lyme disease by the presence of an EM lesion or a positive two-tier Lyme disease serology. To measure seasonal variability, we estimated Fourier regression models to capture cyclical patterns in Lyme disease incidence. While most children with early or early-disseminated Lyme disease presented during the summer months, children with Lyme arthritis presented throughout the year. Clinicians should consider Lyme disease when evaluating children with acute arthritis throughout the year.

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Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease

mSphere ◽

10.1128/msphere.00111-19 ◽

2019 ◽

Vol 4 (3) ◽

Cited By ~ 1

Author(s):

Christina Toumanios ◽

Lauren Prisco ◽

Raymond J. Dattwyler ◽

Paul M. Arnaboldi

Keyword(s):

Amino Acids ◽

Lyme Disease ◽

B Cell ◽

Erythema Migrans ◽

Antibody Binding ◽

Early Infection ◽

Early Disease ◽

B Cell Epitopes ◽

Content Type ◽

Linear B

ABSTRACTBBK32 is a multifunctional surface lipoprotein expressed byBorrelia burgdorferisensu lato,the causative agent of Lyme disease. Previous studies suggested that BBK32 could be a sensitive antigen target of new, more effective, serodiagnostic assays for the laboratory diagnosis of Lyme disease. However, nonspecific antibody binding to full-length BBK32 has hampered its use as a target in clinical assays. Specificity can be improved by the use of peptides composed of linear B cell epitopes that are unique toB. burgdorferi, eliminating cross-reactive epitopes that bind to antibodies generated by non-B. burgdorferiantigens. In this study, we identified linear B cell epitopes in 2 regions, BBK32 amino acids 16 to 30 [BBK32(16–30)] and BBK32 amino acids 51 to 80 [BBK32(51–80)], by probing overlapping peptide libraries of BBK32 with serum from patients with early Lyme disease. We screened synthetic peptides containing these epitopes using a large panel of serum (n = 355) obtained from patients with erythema migrans lesions (early Lyme disease), Lyme arthritis, syphilis, rheumatoid arthritis, or healthy volunteers. BBK32(16–30) demonstrated a nearly universal antibody binding in serum from all patients, indicating that regions of BBK32 are highly cross-reactive. BBK32(51–80) was less cross-reactive, being able to distinguish serum from Lyme disease patients from control patient serum; however, an unacceptable level of antibody binding was still observed in control samples, resulting in a reduced specificity (94.7%). These results indicate that BBK32 contains cross-reactive epitopes that make it a poor antigen target for inclusion in a serodiagnostic assay for Lyme disease and highlight the difficulties in identifying highly sensitive and specific seroassay targets.IMPORTANCELyme disease is an infectious disease that has the potential to cause significant morbidity with damage to nervous and musculoskeletal systems if left untreated. Appropriate antibiotic treatment during early infection prevents disease progression. Unfortunately, currently available diagnostics are suboptimal in the detection of early disease. The inability to confirmBorreliainfection using laboratory methods during early disease is, in part, responsible for much of the controversy surrounding Lyme disease today. As a result, there has been significant investment in the identification of new antigen targets to generate diagnostic assays that are more sensitive for the detection of early infection. The importance of our research is that in our evaluation of BBK32, an antigen that was previously identified as a promising target for use in serodiagnostics, we found a high degree of cross-reactivity that could compromise the specificity of assays that utilize this antigen, leading to false-positive diagnoses.

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Lyme Disease among Patients at an Ambulatory Unit in a Highly Endemic Country: Lithuania

Medicina ◽

10.3390/medicina57020184 ◽

2021 ◽

Vol 57 (2) ◽

pp. 184

Author(s):

Agnė Petrulionienė ◽

Daiva Radzišauskienė ◽

Algimantas Paulauskas ◽

Algirdas Venalis

Keyword(s):

Lyme Disease ◽

Clinical Symptoms ◽

Erythema Migrans ◽

Sensu Stricto ◽

Lyme Arthritis ◽

Middle Aged ◽

Female Ratio ◽

Lyme Carditis ◽

Nervus Facialis ◽

Vilnius University

Background and objectives: Lyme disease is the most common tick-borne infectious disease in Europe, caused by the spirocheta bacteria of Borrelia burgdorferi. Several genospecies of B. burgdorferi are pathogenic to humans. B. burgdorferi sensu stricto, which is prevalent in North America, causes reactive arthritis, whereas B. garinii and B. afzelii, common in Europe, can affect the skin, heart, or nervous system; it has been shown that the clinical symptoms of the disease may be very different. The objective of this study was to identify the baseline characteristics of Lyme disease and to elucidate the frequency of different Lyme disease syndromes in Lithuania. Materials and Methods: Patients who were diagnosed with Lyme disease during an ambulatory visit to the Center of Infectious Diseases, Vilnius University Santaros clinics, from 2014 to 2016, were enrolled in this study. A retrospective material analysis was conducted. Results: In total, 1005 patients were enrolled with the following prevalence of clinical syndromes: erythema migrans (EM), 945 (94.02%); Lyme arthritis, 32 (3.18%); neuroborreliosis, 23 (2.28%); Lyme carditis, 4 (0.39%); and acrodermatitis, 1 (0.09%). Erythema migrans was dominant among middle-aged women, with a rash appearing mainly on the lower extremities. Lyme arthritis mainly manifested among middle-aged women as an oligoarthritis, mostly affecting the knee joint. Neuroborreliosis was seen more often in middle-aged women than men and the main symptom was nervus facialis neuropathy. Lyme carditis, manifested as an atrioventricular block, with a male/female ratio of 3:1, and the median age was 51. Acrodermatitis was diagnosed in a 61-year-old woman, as a painful, red rash on the hand. Conclusions: According to the prevalence of B. garinii and B. afzelii in Europe, previously it was thought that Lyme disease presented as erythema migrans, and less frequently as neuroborreliosis; however, this study revealed that other syndromes may also be seen. In addition, we revealed that the longer it takes for erythema migrans to appear, the greater the likelihood of Lyme arthritis developing.

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A Case of Lyme Disease with Erythema Migrans

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.67.599 ◽

2005 ◽

Vol 67 (6) ◽

pp. 599-603

Author(s):

Sanae KAWAI ◽

Shinya YAMANAKA ◽

Tomomi FUJISAWA ◽

Mariko SEISHIMA ◽

Hiroki KAWABATA

Keyword(s):

Lyme Disease ◽

Erythema Migrans

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Arthritis and Diagnostics in Lyme Disease

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010018 ◽

2021 ◽

Vol 6 (1) ◽

pp. 18

Author(s):

Javier A. Quintero ◽

Raluchukwu Attah ◽

Reena Khianey ◽

Eugenio Capitle ◽

Steven E. Schutzer

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Diagnostic Tests ◽

Laboratory Tests ◽

Diagnostic Methods ◽

Lyme Arthritis ◽

Differential Diagnoses ◽

Antibody Testing ◽

Active Infection ◽

Indirect Measure

The diagnosis of Lyme disease, caused by Borrelia burgdorferi, is clinical but frequently supported by laboratory tests. Lyme arthritis is now less frequently seen than at the time of its discovery. However, it still occurs, and it is important to recognize this, the differential diagnoses, and how laboratory tests can be useful and their limitations. The most frequently used diagnostic tests are antibody based. However, antibody testing still suffers from many drawbacks and is only an indirect measure of exposure. In contrast, evolving direct diagnostic methods can indicate active infection.

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Erythema Migrans Mimicking Cervical Cellulitis with Deep Neck Infection in a Child with Lyme Disease

Journal of the Formosan Medical Association ◽

10.1016/s0929-6646(07)60009-6 ◽

2007 ◽

Vol 106 (7) ◽

pp. 577-581 ◽

Cited By ~ 5

Author(s):

Tsung-Han Li ◽

Chien-Ming Shih ◽

Wei-Jen Lin ◽

Chien-Wei Lu ◽

Li-Lian Chao ◽

...

Keyword(s):

Lyme Disease ◽

Erythema Migrans ◽

Deep Neck Infection ◽

Neck Infection

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Infections Caused by Spirochetes: Syphilis, Lyme Disease, Leptospirosis

10.2310/fm.19049 ◽

2018 ◽

Author(s):

Patrick Duff

Keyword(s):

Lyme Disease ◽

Latent Infection ◽

Congenital Syphilis ◽

Ixodes Scapularis ◽

Severe Disease ◽

Erythema Migrans ◽

Treponema Pallidum ◽

Mild Disease ◽

Drug Of Choice ◽

In Pregnancy

Syphilis is caused by the spirochete Treponema pallidum. It is classified as primary, secondary, tertiary, and latent infection. If left untreated, syphilis can cause devastating injury to the fetus. The drug of choice for treatment of syphilis in pregnancy is penicillin. Lyme disease is caused by Borrelia burgdorferi and is transmitted by the Ixodes scapularis tick. The principal clinical manifestation of Lyme disease is erythema migrans, but patients may also develop arthritis and cardiac and neurologic abnormalities. Congenital Lyme disease has not been reported. The drug of choice for treatment of Lyme disease in pregnancy is amoxicillin. Leptospirosis is usually acquired from direct contact with urine of infected animals or through contaminated water, soil, or vegetation. Pregnant women with mild disease should be treated with oral amoxicillin. Patients with severe disease should be hospitalized and treated with intravenous penicillin or ampicillin. This review contains 5 figures, 5 tables, and 19 references. Key Words: clinical infection, congenital syphilis, latent infection, leptospirosis, Lyme disease, syphilis

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CME: Borrelien-Manifestationen am Bewegungsapparat

Praxis ◽

10.1024/1661-8157/a003665 ◽

2021 ◽

Vol 110 (5) ◽

pp. 231-236

Author(s):

Vittorio Fiore ◽

Julia Rakusa ◽

Thomas Fehr ◽

Jürg Wick

Keyword(s):

Erythema Migrans ◽

Lyme Arthritis

Zusammenfassung. Die Lyme-Borreliose ist die häufigste durch Vektoren übertragene Krankheit in der Schweiz und die Lyme-Arthritis die häufigste Manifestation der Borreliose im Spätstadium. Sie stellt sich als Monoarthitis oder Oligoarthritis in grossen Gelenken dar, wobei das Kniegelenk am häufigsten betroffen ist. Das klinische Bild zusammen mit einer positiven Serologie oder Polymerasekettenreaktionen aus Synovialflüssigkeit/Gewebe bestätigt die Diagnose. Wenn in der Anamnese kein Zeckenstich oder Erythema migrans vorliegt, kann die Diagnosestellung aufgrund der vielen Differenzialdiagnosen eine Herausforderung sein. Die Erstbehandlung ist eine verlängerte Therapie mit oralen Antibiotika.

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Regulatory T Cells Contribute to Resistance against Lyme Arthritis

Infection and Immunity ◽

10.1128/iai.00160-20 ◽

2020 ◽

Vol 88 (11) ◽

Author(s):

Emily M. Siebers ◽

Elizabeth S. Liedhegner ◽

Michael W. Lawlor ◽

Ronald F. Schell ◽

Dean T. Nardelli

Keyword(s):

T Cells ◽

T Cell ◽

Lyme Disease ◽

Regulatory T Cells ◽

Regulatory T Cell ◽

Interleukin 10 ◽

Lyme Arthritis ◽

Interleukin 17 ◽

Content Type

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.

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