Lack ofBorrelia burgdorferi DNA in synovial samples from patients with antibiotic treatment-resistant lyme arthritis

Carlson, David; Hernandez, Jesus; Bloom, Bradley J.; Coburn, Jenifer; Aversa, John M.; Steere, Allen C.

doi:10.1002/1529-0131(199912)42:12<2705::aid-anr29>3.0.co;2-h

Cited by 102 publications

(6 citation statements)

References 12 publications

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“…The clinical manifestations of Lyme borreliosis are believed to be the result of the inflammatory response to infection by B. burgdorferi (Barbour and Fish, 1993;Steere, 1993). Persistence of inflammation with or without residual infection may explain why some patients with Lyme borreliosis remain symptomatic despite treatment with adequate doses of antibiotics (Carlson et al, 1999;Hansen and Lebech, 1992;Oksi et al, 1999;Steere et al, 1983 ). In addition to antibiotics, Lyme borreliosis patients are sometimes given steroids to treat pain syndromes (Oschmann and Dorndorf, 1995), hasten the resolution of facial palsy (Hyden et al, 1993;Sigal, 1992), or treat late neurologic complications of chronic infection (Kruger et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Localization of Borrelia Burgdorferi in the Nervous System and Other Organs in a Nonhuman Primate Model of Lyme Disease

Cadavid

O'Neill

Schaefer

et al. 2000

Laboratory Investigation

112

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SUMMARY:Lyme borreliosis is caused by infection with the spirochete Borrelia burgdorferi. Nonhuman primates inoculated with the N40 strain of B. burgdorferi develop infection of multiple tissues, including the central (CNS) and peripheral nervous system. In immunocompetent nonhuman primates, spirochetes are present in low numbers in tissues. For this reason, it has been difficult to study their localization and changes in expression of surface proteins. To further investigate this, we inoculated four immunosuppressed adult Macaca mulatta with 1 million spirochetes of the N40 strain of B. burgdorferi, and compared them with three infected immunocompetent animals and two uninfected controls. The brain, spinal cord, peripheral nerves, skeletal muscle, heart, and bladder were obtained at necropsy 4 months later. The spirochetal tissue load was first studied by polymerase chain reaction (PCR)-ELISA of the outer surface protein A (ospA) gene. Immunohistochemistry was used to study the localization and numbers of spirochetes in tissues and the expression of spirochetal proteins and to characterize the inflammatory response. Hematoxylin and eosin and trichrome stains were used to study inflammation and tissue injury. The results showed that the number of spirochetes was significantly higher in immunosuppressed animals. B. burgdorferi in the CNS localized to the leptomeninges, nerve roots, and dorsal root ganglia, but not to the parenchyma. Outside of the CNS, B. burgdorferi localized to endoneurium and to connective tissues of peripheral nerves, skeletal muscle, heart, aorta, and bladder. Although ospA, ospB, ospC, and flagellin were present at the time of inoculation, only flagellin was expressed by spirochetes in tissues 4 months later. Significant inflammation occurred only in the heart, and only immunosuppressed animals had cardiac fiber degeneration and necrosis. Plasma cells were abundant in inflammatory foci of steroid-treated animals. We concluded that B. burgdorferi has a tropism for the meninges in the CNS and for connective tissues elsewhere in the body. (Lab Invest 2000, 80:1043-1054.

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Section: Discussionmentioning

confidence: 99%

Localization of Borrelia Burgdorferi in the Nervous System and Other Organs in a Nonhuman Primate Model of Lyme Disease

Cadavid

O'Neill

Schaefer

et al. 2000

Laboratory Investigation

112

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“…Antibiotic‐refractory Lyme arthritis has been hypothesized to result from a small number of remaining spirochetes in synovial tissue (7) or from postinfectious immune phenomena (8). However, after 2–3 months of antibiotic treatment, patients with antibiotic‐refractory arthritis, typically have negative polymerase chain reaction (PCR) results for B burgdorferi DNA in joint fluid or synovial tissue (9, 10), suggesting that Lyme arthritis may persist after the nearly complete or total eradication of spirochetes, perhaps sustained by an infection‐induced autoimmune response.…”

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confidence: 99%

Antibody responses to Borrelia burgdorferi in patients with antibiotic‐refractory, antibiotic‐responsive, or non–antibiotic‐treated lyme arthritis

Kannian

McHugh

Johnson

et al. 2007

Arthritis & Rheumatism

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Objective. To compare the pattern of antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory, antibiotic-responsive, or nonantibiotic-treated Lyme arthritis as an indirect measure of spirochetal persistence or eradication.Methods. At least 3 serial serum samples from 41 patients with antibiotic-refractory arthritis and 23 patients with antibiotic-responsive arthritis, and samples from 10 non-antibiotic-treated, historical control patients were tested for IgG reactivity with B burgdorferi sonicate and 4 differentially expressed outer surface lipoproteins of the spirochete, by enzyme-linked immunosorbent assay.Results. Among non-antibiotic-treated patients, antibody titers to B burgdorferi antigens remained high throughout a 2-5-year period of arthritis. In contrast, in patients with antibiotic-responsive arthritis, in whom joint swelling usually resolved during a 1-month course of oral antibiotic therapy, the median antibody titers to most of the spirochetal antigens remained steady or decreased during the first 1-3 months after starting antibiotic therapy. In patients with antibiotic-refractory arthritis, who had persistent joint swelling for a median duration of 10 months despite 2-3 months of oral or intravenous antibiotics, the median titers to most antigens increased slightly during the first 1-3 months. However, by 4-6 months after starting antibiotic therapy, reactivity with all antigens declined similarly in both antibiotic-treated groups.Conclusion. Whereas the antibody titers to B burgdorferi remained high in non-antibiotic-treated patients, the titers declined similarly 4-6 months after starting therapy in patients with antibiotic-responsive or antibiotic-refractory arthritis, suggesting that synovial inflammation persisted in patients with antibioticrefractory arthritis after the period of infection.

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“…One manifestation of the disease is arthritis, which can result in chronic arthritis in a small subset of exposed individuals [13]. The prevalence of HLA-DR4 related alleles in these patients is an indication of an autoimmune process [13,14]. …”

Section: Discussionmentioning

confidence: 99%

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients

et al. 2012

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BackgroundMany autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage – erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers.ResultsThe results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p < 0.007) and HLA-DRB1 *17 (03) (OR 8.05; p < 0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p < 0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect.ConclusionsHLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population

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Lack ofBorrelia burgdorferi DNA in synovial samples from patients with antibiotic treatment-resistant lyme arthritis

Cited by 102 publications

References 12 publications

Localization of Borrelia Burgdorferi in the Nervous System and Other Organs in a Nonhuman Primate Model of Lyme Disease

Localization of Borrelia Burgdorferi in the Nervous System and Other Organs in a Nonhuman Primate Model of Lyme Disease

Antibody responses to Borrelia burgdorferi in patients with antibiotic‐refractory, antibiotic‐responsive, or non–antibiotic‐treated lyme arthritis

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients

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