Strong IgG antibody responses to Borrelia burgdorferi glycolipids in patients with Lyme arthritis, a late manifestation of the infection

Jones, Kathryn L.; Seward, Robert J.; Ben-Menachem, Gil; Glickstein, Lisa J.; Costello, Catherine E.; Steere, Allen C.

doi:10.1016/j.clim.2009.03.510

Cited by 24 publications

(20 citation statements)

References 27 publications

(36 reference statements)

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“…Antibody responses to these glycolipids have been detected throughout the course of Lyme disease [9], [11], [12], [20]. To observe the role of cholesterol and cholesterol-glycolipids of B. burgdorferi , we developed methods to incorporate labeled cholesterol into the spirochetal membranes and showed that the labeled cholesterol is used as a substrate for synthesis of the cholesterol-glycolipids.…”

Section: Discussionmentioning

confidence: 99%

“…Important to the pathogenesis of B. burgdorferi , ACGal, and to a lesser extent MGalD and CGal, are antigenic [13], [15]–[17], [19]. These glycolipids induce antibody responses throughout all stages of Lyme disease, being most prominent in the late stages [9], [11], [12], [20], [21]. Additionally, we demonstrated that antibodies to the cholesterol-glycolipids cross-react with host gangliosides and antibodies to the gangliosides cross-react with the glycolipids [22], [23].…”

Section: Introductionmentioning

confidence: 99%

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Lipid Exchange between Borrelia burgdorferi and Host Cells

et al. 2013

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Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or 3H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid Exchange between Borrelia burgdorferi and Host Cells

et al. 2013

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“…Months later, untreated patients commonly develop Lyme arthritis (LA) [2]. As the infection progresses, patients develop antibody responses to an increasing array of spirochetal proteins and glycolipids [3, 4]. Although most LA patients respond to antibiotic therapy, called antibiotic-responsive LA, a small percentage of patients have persistent synovitis for months or years after 2–3 months of oral and intravenous antibiotic therapy, termed antibiotic-refractory LA [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis

Pianta¹,

Drouin²,

Crowley³

et al. 2015

Clinical Immunology

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In this study, autoantibody responses to annexin A2 were found in 11–15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (LA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings.

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“…11,12 In mice and rabbits, BBGL-2 elicited antibodies that reacted with both BBGL-1 and -2, and the sera of LD patients had a strong IgG reaction with BBGL-2. 11,16 These propensities make the BBGL-2 glycolipids candidates for developing diagnostics and vaccines against B. burgdorferi devoid of any immunogenic proteins such as L-OspA that might have the potential to elicit autoantibodies. 5 …”

Section: Introductionmentioning

confidence: 99%

Synthesis and antigenicity of BBGL-2 glycolipids of Borrelia burgdorferi, the causative agent of Lyme disease

Pozsgay

Kübler-Kiełb

Coxon

et al. 2011

Carbohydrate Research

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Borrelia burgdorferi is the etiological agent for Lyme disease (LD), the most common vector borne disease in the United States. There is no human vaccine against LD currently available. Our approach to a vaccine is based on its surface-exposed glycolipids. One group of these glycolipids termed BBGL-2 consists of 1,2-di-O-acyl-3-O-(α-D-galactopyranosyl)-sn-glycerol congeners having palmitic, oleic, stearic, linoleic, and myristic acids. In order to delineate the immunodominant region(s) of the BBGL-2 components, we embarked on a synthetic project to provide available structurally defined, homogeneous analogs of BBGL-2 that might help identify the best vaccine candidate. The antigenicity of the synthetic glycolipids was examined by dot-blot analysis using mice sera obtained by immunization with killed B. burgdorferi cells, with native BBGL-2 in complete Freund's adjuvant, as well as sera obtained from patients with Lyme disease. We found that the presence of two acyl groups in the glycerol moiety was essential for antigenicity. At least one of these groups must be an oleoyl moiety. Neither the anomeric configuration of the galactose nor the configuration of the glycerol at C-2 was a decisive factor. Based on these findings we designed an `unnatural' BBGL-2 analog having the structure 3-O-(β-D-galactopyranosyl)-1,2-di-O-oleoyl-DL-glycerol which is easier and less expensive to synthesize than the other BBGL-2 congeners prepared in this study. This substance proved to be antigenic and is considered a candidate vaccine for Lyme disease.

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Strong IgG antibody responses to Borrelia burgdorferi glycolipids in patients with Lyme arthritis, a late manifestation of the infection

Cited by 24 publications

References 27 publications

Lipid Exchange between Borrelia burgdorferi and Host Cells

Lipid Exchange between Borrelia burgdorferi and Host Cells

Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis

Synthesis and antigenicity of BBGL-2 glycolipids of Borrelia burgdorferi, the causative agent of Lyme disease

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