34 results match your criteria treatment-resistant lyme


Cytokine Expression Patterns and Single Nucleotide Polymorphisms (SNPs) in Patients with Chronic Borreliosis.

Antibiotics (Basel) 2019 Jul 30;8(3). Epub 2019 Jul 30.

Division of Experimental Anesthesiology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.

(1) Background: Genetically based hyperinflammation may play a role in pathogen defense. We here questioned whether alterations in circulating monocytes/macrophages, inflammatory biomarkers and a functional SNP (single nucleotide polymorphisms) of the Interleukin-6 (IL-6) promotor might play a role in patients with persistent, and treatment resistant borreliosis. (2) Methods: Leukocyte subpopulations were studied by flow cytometry; plasma cytokines were determined by a chemiluminescence based ELISA (Immulite), and genotypes of the IL-6 promotor SNP rs1800795 were determined by pyrosequencing. Read More

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HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination.

Arthritis Rheum 2009 Apr;60(4):1179-86

Center for Biologics Evaluation and Research, FDA, Rockville, Maryland, USA.

Objective: To investigate whether persons with treatment-resistant Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen.

Methods: Persons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA-DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed. Read More

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Clonal diversification in OspA-specific antibodies from peripheral circulation of a chronic Lyme arthritis patient.

J Immunol Methods 2007 Apr 6;321(1-2):121-34. Epub 2007 Feb 6.

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, Massachusetts 02111, USA.

Chronic, antibiotic treatment-resistant Lyme arthritis develops in a subset of patients following infection with the tick-borne spirochete Borrelia burgdorferi and persists after apparent microbial clearance. IgG responses to Outer Surface Protein (Osp) A, an abundant spirochetal lipoprotein, correlate with both severity and duration of joint inflammation. Characterization of this OspA-directed antibody response is, therefore, important for understanding some of the mechanisms that sustain persistent pathology. Read More

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Antimicrobial susceptibility of Borrelia burgdorferi sensu lato: what we know, what we don't know, and what we need to know.

Wien Klin Wochenschr 2006 Nov;118(21-22):659-68

Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt/Main, Germany.

Human Lyme borreliosis is a multisystem disorder that can progress in stages and is transmitted by ticks of the Ixodes ricinus complex infected with the spirochete Borrelia burgdorferi sensu lato. Today, Lyme borreliosis is regarded as the most important human tickborne illness in the northern hemisphere. Soon after the causative agent was correctly identified and successfully isolated in 1982, antibiotic treatment was shown to be effective and since then a variety of in vitro and in vivo studies have been performed to further characterize the activity of antimicrobial agents against B. Read More

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November 2006

Cerebrospinal fluid-infiltrating CD4+ T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early lyme encephalitis.

Infect Immun 2007 Jan 23;75(1):243-51. Epub 2006 Oct 23.

Neuroimmunology Branch, Cellular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.

Neurological manifestations of Lyme disease are usually accompanied by inflammatory changes in the cerebrospinal fluid (CSF) and the recruitment of activated T cells into the CSF compartment. In order to characterize the phenotype and identify target antigens of CSF-infiltrating T cells in early neuroborreliosis with central nervous system (CNS) involvement, we combined T-cell cloning, functional testing of T-cell responses with positional scanning synthetic combinatorial peptide libraries, and biometric data analysis. We demonstrate that CD4+ gamma interferon-producing T cells specifically responding to Borrelia burgdorferi lysate were present in the CSF of a patient with acute Lyme encephalitis. Read More

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January 2007

Autoantibodies from synovial lesions in chronic, antibiotic treatment-resistant Lyme arthritis bind cytokeratin-10.

J Immunol 2006 Aug;177(4):2486-94

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

Although the causative agent of Lyme disease is definitively known to be the tick-borne spirochete, Borrelia burgdorferi, the etiology of chronic joint inflammation that ensues in a subset of patients remains less well understood. Persistence of arthritis after apparent eradication of the spirochete suggests an autoimmune reaction downstream of the original bacterial infection. We have generated recombinant Ab probes from synovial lesions within affected arthritic joints in an attempt to recapitulate disease-relevant Ag-binding specificities at the site of injury. Read More

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Characterization of in vivo expanded OspA-specific human T-cell clones.

Clin Immunol 2005 Jun;115(3):313-22

Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

A panel of CD4 T-cell clones was isolated from synovial fluid by single cell flow cytometry from a patient with treatment-resistant Lyme arthritis using a DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with outer surface protein A (OspA) peptide164-175, an immunodominant epitope of Borrelia burgdorferi. Sequencing of the T-cell receptors of the OspA reactive clones showed significant skewing of the T-cell receptor repertoire. Of the 101 T-cell clones sequenced, 81 possessed TCR beta chains that were present in at least one other clone isolated. Read More

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Molecular characterization of the OspA(161-175) T cell epitope associated with treatment-resistant Lyme arthritis: differences among the three pathogenic species of Borrelia burgdorferi sensu lato.

J Autoimmun 2004 Nov;23(3):281-92

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Treatment-resistant Lyme arthritis, which may result from infection-induced autoimmunity, is associated with reactivity to a T cell epitope of outer-surface protein A (OspA(161-175)) of Borrelia burgdorferi sensu stricto (Bb). This syndrome has been noted primarily in the United States where only Bb is present, and rarely in Europe where Borrelia garinii (Bg) and Borrelia afzelii (Ba) predominate. To gain a better understanding of this epitope, we identified its species-specific polymorphisms, determined their immunogenicity, and characterized the contribution of individual amino acids. Read More

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November 2004

An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope.

Proc Natl Acad Sci U S A 2004 Feb 23;101(5):1303-8. Epub 2004 Jan 23.

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

The antigenic component of a common Lyme disease vaccine is recombinant outer surface protein A (rOspA) of Borrelia burgdorferi (Bb), the causative agent of Lyme disease. Coincidentally, patients with chronic, treatment-resistant Lyme arthritis develop an immune response against OspA, whereas those with acute Lyme disease usually do not. Treatment-resistant Lyme arthritis occurs in a subset of Lyme arthritis patients and is linked to HLA. Read More

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February 2004

Lyme disease (Lyme borreliosis).

Best Pract Res Clin Rheumatol 2003 Apr;17(2):241-64

Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.

Lyme borreliosis (Lyme disease) is a systemic infectious disease with a wide spectrum of symptoms affecting the skin, the heart, and the nervous and musculoskeletal systems. Lyme borreliosis is caused by the spirochaete Borrelia burgdorferi and transmitted by ticks. The disease occurs in endemic pockets with an incidence of from 50 to more than 100 cases per 100,000 inhabitants. Read More

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Binding of outer surface protein A and human lymphocyte function-associated antigen 1 peptides to HLA-DR molecules associated with antibiotic treatment-resistant Lyme arthritis.

Arthritis Rheum 2003 Feb;48(2):534-40

Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts, USA.

Objective: To assess the binding of outer surface protein A (OspA) and human lymphocyte function-associated antigen 1 (hLFA-1) peptides to 5 major histocompatibility complex (MHC) molecules.

Methods: Peptide binding to the MHC molecules was determined by in vitro binding assays, and binding was correlated with the frequencies of the 5 MHC molecules in patients with treatment-resistant Lyme arthritis.

Results: The HLA-DRB1*0401 molecule bound both OspA(163-175) and hLFA-1alpha(L330-342) well. Read More

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February 2003

Development of autoimmunity in Lyme arthritis.

Curr Opin Rheumatol 2002 Jul;14(4):388-93

Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Treatment-resistant Lyme arthritis (TRLA) develops in 10% of Lyme arthritis patients and is characterized by continuous joint inflammation that does not resolve with antibiotic therapy. TRLA is associated with HLA-DRB1*0401 and related alleles, as well as with an immune response to the Borrelia burgdorferi (Bb) outer surface protein A (OspA). The immunodominant epitope of OspA in the context of HLA-DRB1*0401 corresponds to amino acids 165-173 (OspA165-173). Read More

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Lyme arthritis.

Med Clin North Am 2002 Mar;86(2):297-309

Tufts University School of Medicine, Itzhak Perlman Family Arthritis Treatment Center, Division of Rheumatology, New England Medical Center, Boston, Massachusetts, USA.

Infection with B. burgdorferi can cause a large joint inflammatory arthritis in patients who have not been treated for early Lyme disease; the knee is the most common joint affected. The diagnosis depends on a history of known exposure to the spirochete, characteristic clinical features, and serologic studies (ELISA and Western blot) confirming exposure to the spirochete. Read More

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Antibody response to IR6, a conserved immunodominant region of the VlsE lipoprotein, wanes rapidly after antibiotic treatment of Borrelia burgdorferi infection in experimental animals and in humans.

J Infect Dis 2001 Oct 30;184(7):870-8. Epub 2001 Aug 30.

Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 70433, USA.

Invariable region (IR)(6), an immunodominant conserved region of VlsE, the antigenic variation protein of Borrelia burgdorferi, is currently used for the serologic diagnosis of Lyme disease in humans and canines. A longitudinal assessment of anti-IR(6) antibody levels in B. burgdorferi-infected rhesus monkeys revealed that this level diminished sharply after antibiotic treatment (within 25 weeks). Read More

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October 2001

Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis.

J Autoimmun 2001 May;16(3):263-8

Division of Rheumatology/Immunology (Medicine) and the Department of Pathology, Tufts University School of Medicine, New England Medical Center, Boston, MA, USA.

In about 10% of patients with Lyme arthritis in the United States, joint inflammation persists for months or even several years after the apparent eradication of the spirochete, Borrelia burgdorferi, from the joint with antibiotic treatment. We propose a model of molecular mimicry affecting genetically susceptible individuals to explain this treatment-resistant course. The majority of patients with treatment-resistant Lyme arthritis have HLA-DRB1*0401 or related alleles, and the severity and duration of their arthritis correlate with cellular and humoral immune responses to outer-surface protein A OspA) of the spirochete. Read More

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Molecular mimicry in Lyme arthritis demonstrated at the single cell level: LFA-1 alpha L is a partial agonist for outer surface protein A-reactive T cells.

J Immunol 2001 Apr;166(8):5286-91

Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Antibiotic treatment-resistant Lyme arthritis is a chronic inflammatory joint disease that follows infection with Borrelia burgdorferi (BB:). A marked Ab and T cell response to BB: outer surface protein A (OspA) often develops during prolonged episodes of arthritis. Furthermore, cross-reaction between the bacterial OspA and human LFA-1alpha(L) at the T cell level and the inability to detect BB: in the joint implicate an autoimmune mechanism. Read More

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Expression of adhesion molecules in synovia of patients with treatment-resistant lyme arthritis.

Infect Immun 2001 Mar;69(3):1774-80

Division of Rheumatology/Immunology, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.

The expression of adhesion molecules in synovium in patients with Lyme arthritis is surely critical in the control of Borrelia burgdorferi infection but may also have pathologic consequences. For example, molecular mimicry between a dominant T-cell epitope of B. burgdorferi outer surface protein A and an adhesion molecule, human lymphocyte function-associated antigen 1 (LFA-1), has been implicated in the pathogenesis of treatment-resistant Lyme arthritis. Read More

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Treatment resistant Lyme arthritis caused by Borrelia garinii.

Ann Rheum Dis 2001 Mar;60(3):284-6

Rheumatology Department, Hôpitaux Universitaires de Strasbourg, France.

Lyme arthritis is caused in Europe by three main pathogenic species of Borrelia burgdorferi sensu lato: Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. Because few synovial samples have yet been analysed by species-specific DNA amplification methods, further studies are needed to define the spectra of clinical manifestations associated with these different species. Two cases of treatment resistant Lyme arthritis are reported here, in which DNA amplification of the flagellin gene followed by dot-blot hybridisation in the synovial fluid identified B garinii as the causative agent. Read More

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Cellular and molecular aspects of Lyme arthritis.

Authors:
D M Gross B T Huber

Cell Mol Life Sci 2000 Oct;57(11):1562-9

Department of Pathology, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Lyme disease is a multisystem illness initiated upon infection with the spirochete Borrelia burgdorferi. Whereas the majority of patients who develop Lyme arthritis may be successfully treated with antibiotic therapy, about 10% go on to develop arthritis which persists for months to years, despite antibiotic therapy. Development of what we have termed treatment-resistant Lyme arthritis has previously been associated with both the presence of particular major histocompatibility complex class II alleles and immunoreactivity to the spriochetal outer surface protein A (OspA). Read More

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October 2000

Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers.

Proc Natl Acad Sci U S A 2000 Oct;97(21):11433-8

Tufts University School of Medicine, Department of Pathology, Boston, MA 02111, USA.

We characterized antigen-specific CD4(+) T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with OspA(164-175), an immunodominant epitope of Borrelia burgdorferi. Direct analysis of OspA-tetramer binding CD4(+) cells in patients expressing the HLA-DRB1*0401 allele revealed frequencies of between <0.005 and 0. Read More

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October 2000

Lyme disease 2000. Emerging zoonoses complicate patient work-up and treatment.

Authors:
R A Terkeltaub

Geriatrics 2000 Jul;55(7):34-5, 39-40, 43-4 passim

University of California, San Diego, USA.

Lyme disease and other tick-borne diseases affect all age groups, including active persons age 50 and older. There has been a steady expansion in case numbers and the geographic borders of Lyme disease over the last two decades. Better recognition of two emerging tick-borne zoonoses (babesiosis and human granulocytic ehrlichiosis) that can be co-transmitted with Lyme disease is changing the approach to diagnosis and treatment of Lyme disease. Read More

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Studies on the pathogenesis and treatment of Lyme arthritis.

Wien Klin Wochenschr 1999 Dec;111(22-23):981-4

Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Federal Republic of Germany.

Lyme arthritis is one of the most common clinical manifestations of Lyme borreliosis. It is caused by an intraarticular infection with Borrelia (B.) burgdorferi. Read More

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December 1999

Lack of Borrelia burgdorferi DNA in synovial samples from patients with antibiotic treatment-resistant Lyme arthritis.

Arthritis Rheum 1999 Dec;42(12):2705-9

Tufts University School of Medicine, New England Medical Center, Tupper Research Institute, Boston, Massachusetts 02111, USA.

Objective: To determine whether Borrelia burgdorferi DNA may be detected in synovial tissue from patients with Lyme arthritis who have persistent synovial inflammation after antibiotic treatment.

Methods: Synovial specimens obtained at synovectomy from 26 patients with antibiotic treatment-resistant Lyme arthritis and from 10 control subjects were tested for B burgdorferi DNA using 3 primer-probe sets that target genes encoding outer surface proteins A or B or a flagellar protein (P41) of the spirochete.

Results: The 26 patients with Lyme arthritis, who had received antibiotic therapy for a mean total duration of 8 weeks prior to synovectomy, and the 10 control subjects each had negative polymerase chain reaction (PCR) results in synovial samples. Read More

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December 1999

Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi.

Arthritis Rheum 1999 Sep;42(9):1813-22

Tufts University School of Medicine, Boston, Massachusetts, USA.

Objective: To explore further the association of antibiotic treatment-resistant Lyme arthritis and T cell reactivity with outer surface protein A (OspA) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment-resistant course.

Methods: The responses of peripheral blood and, if available, synovial fluid lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon-gamma production, were compared in 16 patients with treatment-responsive and 16 with treatment-resistant Lyme arthritis.

Results: The maximum severity of joint swelling correlated directly with the response to OspA. Read More

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September 1999

Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis.

Science 1998 Jul;281(5377):703-6

Department of Pathology, Tufts University, Boston, MA 02111 USA.

Treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of Borrelia burgdorferi, the agent of Lyme disease, and the major histocompatibility complex class II allele DRB1*0401. The immunodominant epitope of OspA for T helper cells was identified. A homology search revealed a peptide from human leukocyte function-associated antigen-1 (hLFA-1) as a candidate autoantigen. Read More

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Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy.

Ann Rheum Dis 1998 Feb;57(2):118-21

Charité University Hospital, Department of Medicine III, Rheumatology and Clinical Immunology, Berlin, Germany.

Objectives: To identify possible sites of bacterial persistence in patients with treatment resistant Lyme arthritis. It was determined whether Borrelia burgdorferi DNA may be detectable by polymerase chain reaction (PCR) in synovial membrane (SM) when PCR results from synovial fluid (SF) had become negative after antibiotic therapy.

Methods: Paired SF and SM specimens and urine samples from four patients with ongoing or recurring Lyme arthritis despite previous antibiotic therapy were investigated. Read More

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February 1998

T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis.

J Immunol 1998 Jan;160(2):1022-8

Tufts University School of Medicine, Department of Pathology, Boston, MA 02111, USA.

Cytokines produced by subsets of CD4+ T helper cells responding to an infection influences the efficiency with which the host is able to mount a protective immune response. In an attempt to elucidate the population of active cells involved in the propagation of Lyme arthritis we have utilized intracellular cytokine staining to analyze the polyclonal immune response at the single cell level. We have determined the Th phenotype in the synovial fluid of patients with a variety of chronic inflammatory arthritides, including patients representative of the spectrum of Lyme arthritis. Read More

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January 1998

Host-pathogen interactions in the immunopathogenesis of Lyme disease.

Authors:
L T Hu M S Klempner

J Clin Immunol 1997 Sep;17(5):354-65

Tupper Research Institute, Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

The immunopathogenesis of Lyme disease is complicated and requires a thorough understanding of the interaction among the causative organism, Borrelia burgdorferi, its tick vector, and its mammalian hosts. In vitro, animal and human studies have shown that the organism is capable of adapting to and utilizing elements from its environment to establish infection and persist despite a inducing a strong immune response. Indeed, the immune response may be responsible for many of the symptoms associated with Lyme disease. Read More

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September 1997

Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.

J Immunol 1996 Dec;157(12):5496-502

Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.

Lyme disease, due to infection with the tick-borne spirochete Borrelia burgdorferi, is a multisystem disorder that can lead to chronic disabling symptoms. Abs to the outer surface protein A (OspA) of B. burgdorferi provide protection against infection, and OspA is now the basis of a first generation recombinant vaccine undergoing phase III efficacy studies. Read More

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December 1996