Molecular mimicry and lyme borreliosis: A shared antigenic determinant between <i>Borrelia burgdorferi</i> and human tissue

Aberer, Elisabeth; Brunner, Christof; Suchanek, Gerda; Klade, H; Barbour, Alan G.; Stanek, Gerold; Lassmann, Hans

doi:10.1002/ana.410260608

Cited by 119 publications

(47 citation statements)

References 30 publications

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“…burgdorferi may be a safer starting point for a vaccine for protection against Lyme disease. Demonstrations of antigenic cross-reactions between flagellar-associated antigens and human tissues, including nerve and muscle (25,26), suggest that vaccines containing even small amounts of flagellar materials may induce an autoimmune reaction in the recipient. Another possible advantage of an immunogen preparation lacking flagella is that antibodies to flagella, or, better, antibodies to pathogen-specific peptides of flagella, can be used to assess the efficacy of the vaccine.…”

Section: Discussionmentioning

confidence: 99%

A flagella-less mutant of Borrelia burgdorferi. Structural, molecular, and in vitro functional characterization.

Sadziene

Thomas²,

Bundoc³

et al. 1991

J. Clin. Invest.

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A nonmotile mutant of Borrelia burgdorferi, the etiologic agent of Lyme disease, was isolated and characterized. The mutant was compared with the wild-type predecessor as well as with a motile back-revertant of the same genetic background. The mutant lacked, by morphologic, biochemical, and immunologic criteria, the major structural protein of flagella, flagellin. This mutation was not associated with major DNA rearrangements or with failure of transcription. An apparent consequence of a loss of flagella was reduced ability to penetrate human endothelial cell layers in vitro. In another assessment of functional significance, the flagella-less mutant was equal if not superior to flagella-bearing, isogenic isolates when examined in an enzyme-linked immunosorbent assay for anti-B. burgdorferi antibodies in the sera of Lyme disease patients. These studies of a mutant, the first among pathogenic Borrelia spp. to be characterized, indicate that the flagellum and motility it confers play a role in B. burgdorferi's invasion of human tissues. A flagellaless B. burgdorferi may be useful as the basis of a more specific immunoassay and a vaccine for protection against Lyme disease. (J. Clin. Invest. 1991. 88:82-92.)

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Section: Discussionmentioning

confidence: 99%

A flagella-less mutant of Borrelia burgdorferi. Structural, molecular, and in vitro functional characterization.

Sadziene

Thomas²,

Bundoc³

et al. 1991

J. Clin. Invest.

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“…Unfortunately, although highly immunogenic, this antigen is highly cross-reactive with antigens in other bacteria, particularly when denatured, as in immunoblots (35,91,179). Certain flagellin epitopes are also cross-reactive with antigens found in mammalian tissues such as neural tissues, synovium, and myocardial muscle (1,179). The internal portion of the flagellin molecule, containing the variable, genus-specific immunodominant domain, is less cross-reactive with antigens of other bacteria than the whole protein (101,179,274).…”

Section: Immunologic Diagnosis Of B Burgdorferi Sensu Lato Infectionmentioning

confidence: 99%

Diagnosis of Lyme Borreliosis

et al. 2005

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A large amount of knowledge has been acquired since the original descriptions of Lyme borreliosis (LB) and of its causative agent, Borrelia burgdorferi sensu stricto. The complexity of the organism and the variations in the clinical manifestations of LB caused by the different B. burgdorferi sensu lato species were not then anticipated. Considerable improvement has been achieved in detection of B. burgdorferi sensu lato by culture, particularly of blood specimens during early stages of disease. Culturing plasma and increasing the volume of material cultured have accomplished this. Further improvements might be obtained if molecular methods are used for detection of growth in culture and if culture methods are automated. Unfortunately, culture is insensitive in extracutaneous manifestations of LB. PCR and culture have high sensitivity on skin samples of patients with EM whose diagnosis is based mostly on clinical recognition of the lesion. PCR on material obtained from extracutaneous sites is in general of low sensitivity, with the exception of synovial fluid. PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. Currently, the best use of PCR is for confirmation of the clinical diagnosis of suspected Lyme arthritis in patients who are IgG immunoblot positive. PCR should not be used as the sole laboratory modality to support a clinical diagnosis of extracutaneous LB. PCR positivity in seronegative patients suspected of having late manifestations of LB most likely represents a false-positive result. Because of difficulties in direct methods of detection, laboratory tests currently in use are mainly those detecting antibodies to B. burgdorferi sensu lato. Tests used to detect antibodies to B. burgdorferi sensu lato have evolved from the initial formats as more knowledge on the immunodominant antigens has been collected. The recommendation for two-tier testing was an attempt to standardize testing and improve specificity in the United States. First-tier assays using whole-cell sonicates of B. burgdorferi sensu lato need to be standardized in terms of antigen composition and detection threshold of specific immunoglobulin classes. The search for improved serologic tests has stimulated the development of recombinant protein antigens and the synthesis of specific peptides from immunodominant antigens. The use of these materials alone or in combination as the source of antigen in a single-tier immunoassay may someday replace the currently recommended two-tier testing strategy. Evaluation of these assays is currently being done, and there is evidence that certain of these antigens may be broadly cross-reactive with the B. burgdorferi sensu lato species causing LB in Europe

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“…It is very interesting that drugs and bacterial or viral agents are able to provoke antigen mimicry, directly or indirectly [3]. Several diseases have been reported to be possibly associated with the mechanism of molecular mimicry, such as insulin dependent diabetes, multiple sclerosis, myasthenia gravis, pemphigus, Lyme diseases, syphilis, celiac disease, autoimmune uveitis [11,12]. Moreover, Bramanti, Sugerman and Chaiyarit, identified up-regulated heat-shock protein (HSP) expression by oral LP (OLP) lesional keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2014

Glob Dermatol

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Lichen Planus (LP) is a chronic mucocutaneous disease with several variants defined by the configuration of lesions, the morphological appearance, and the site of involvement. Although exact cause of LP is not known, it is thought that it is most likely an immunologically mediated reaction especially a cell-mediated immune response of unknown origin. Typical lesion is seen as a pruritic, papular eruption characterized by its violaceous color; polygonal shape; and, sometimes, fine scale. The size can vary from 1 mm to greater than 1 cm in diameter . It is most commonly found on the flexor surfaces of the upper extremities, on the genitalia, and on the mucous membranes. The clinical presentation of the disease has several forms: actinic, annular, atrophic, erosive, follicular, hypertrophic, linear, pigmented, vesicular/ bullous and eruptive/exanthematous. "Exanthematous" or "eruptive" LP is a rare variant of the disease. Herein we report a 15 year-old boy, and a 32-year old man with a 1.5 and 3-month history respectively, of acute, episodic and eruptive mucocutaneous LP after a toluene exposure. To the best of our knowledge, our patients are the first cases of exanthematous mucocutaneous lichen planus that were caused by toluene exposure.

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Molecular mimicry and lyme borreliosis: A shared antigenic determinant between Borrelia burgdorferi and human tissue

Cited by 119 publications

References 30 publications

A flagella-less mutant of Borrelia burgdorferi. Structural, molecular, and in vitro functional characterization.

A flagella-less mutant of Borrelia burgdorferi. Structural, molecular, and in vitro functional characterization.

Diagnosis of Lyme Borreliosis

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