Antiphospholipid autoantibodies in Lyme disease arise after scavenging of host phospholipids by Borrelia burgdorferi

Gwynne, Peter; Clendenen, Luke H; Turk, Siu-Ping; Marques, Adriana; Hu, Linden T.

doi:10.1172/jci152506

Cited by 16 publications

(17 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…also described three novel lipid and phospholipid antibodies that were found in nearly all patients with untreated, acute LD. 13 Similar to the anti-AA2 antibodies in our study, these lipid/phospholipid antibodies often decreased after antimicrobial therapy. 13 However, the lipid/phospholipid antibodies were also assessed in a small group of patients with persistent symptoms after LD, and 33% [4 of 12] of these patients still had antibodies, up to 13 years after LD diagnosis and treatment.…”

Section: Discussionsupporting

confidence: 80%

Annexin A2 antibodies in post-treatment Lyme disease

Miller,

Rebman,

de Flores

et al. 2024

Therapeutic Advances in Infection

View full text Add to dashboard Cite

Background: Anti-annexin A2 (AA2) antibodies have been described in Lyme arthritis and erythema migrans, although they have not been described in post-treatment Lyme disease (PTLD). Objectives: Determine whether anti-AA2 antibodies are present among patients with PTLD and determine the clinical relevance of these antibodies. Design and methods: Anti-AA2 levels were tested serially in a longitudinal cohort of 44 patients with acute Lyme disease, 22 with a return to health (EM RTH), and 22 with PTLD. Anti-AA2 antibodies were also assessed in a cross-sectional group of 281 patients with PTLD. Results: Anti-AA2 antibodies were highest after antimicrobial therapy in both the EM RTH and PTLD cohorts. By 6 months, there was no difference between EM RTH and healthy controls. Anti-AA2 antibodies were higher in the cross-sectional PTLD group (79.69 versus 48.22 units, p < 0.0001), though with no difference in total symptom burden. Conclusion: Anti-AA2 persists in PTLD, though did not identify a clinical phenotype.

show abstract

Section: Discussionsupporting

confidence: 80%

Annexin A2 antibodies in post-treatment Lyme disease

Miller,

Rebman,

de Flores

et al. 2024

Therapeutic Advances in Infection

View full text Add to dashboard Cite

show abstract

“…Borrelia spp. scavenge host lipids and rely on their arthropod vectors and mammalian hosts to complete their life cycles ( 1 , 2 , 14 – 17 ). B. burgdorferi requires palmitate, oleate, and cholesterol for bacterial growth ( 15 – 22 ).…”

Section: Resultsmentioning

confidence: 99%

“…scavenge host lipids and rely on their arthropod vectors and mammalian hosts to complete their life cycles ( 1 , 2 , 14 – 17 ). B. burgdorferi requires palmitate, oleate, and cholesterol for bacterial growth ( 15 – 22 ). Therefore, we hypothesized that B. burgdorferi infection would affect the lipidome of tick cells.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Croquemort elicits activation of the immune deficiency pathway in ticks

O’Neal

Singh

Rolandelli

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The immune deficiency (IMD) pathway directs host defense in arthropods upon bacterial infection. In Pancrustacea, peptidoglycan recognition proteins sense microbial moieties and initiate nuclear factor-κB-driven immune responses. Proteins that elicit the IMD pathway in non-insect arthropods remain elusive. Here, we show that an Ixodes scapularis homolog of croquemort (Crq), a CD36-like protein, promotes activation of the tick IMD pathway. Crq exhibits plasma membrane localization and binds the lipid agonist 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoglycerol. Crq regulates the IMD and jun N-terminal kinase signaling cascades and limits the acquisition of the Lyme disease spirochete B. burgdorferi . Additionally, nymphs silenced for crq display impaired feeding and delayed molting to adulthood due to a deficiency in ecdysteroid synthesis. Collectively, we establish a distinct mechanism for arthropod immunity outside of insects and crustaceans.

show abstract

“…For example, the increase in expression of Salp15, a tick salivary immunomodulator, was shown to enhance B. burgdorferi transmission to the murine host ( Ramamoorthi et al., 2005 ). Due to the reduced genome of B. burgdorferi , it has to scavenge nutrients such as carbohydrates, amino acids and lipids from it arthropod or mammalian host ( Corona and Schwartz, 2015 ; Kerstholt et al., 2020 ; Gwynne et al., 2022 ). Whether the impact of B. burgdorferi on metabolic pathways of the tick ( Corona and Schwartz, 2015 ) and consequent changes in nutritional reserves could have consequences on tick survival, development timing, respiration, locomotion, host-seeking and fecundity remains to be experimentally verified.…”

Section: Tick- B Burgdorferi Interactionsmentioning

confidence: 99%

The environment, the tick, and the pathogen – It is an ensemble

Couret

Schofield

Narasimhan

2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Ixodes scapularis is one of the predominant vectors of Borrelia burgdorferi, the agent of Lyme disease in the USA. The geographic distribution of I. scapularis, endemic to the northeastern and northcentral USA, is expanding as far south as Georgia and Texas, and northwards into Canada and poses an impending public health problem. The prevalence and spread of tick-borne diseases are influenced by the interplay of multiple factors including microbiological, ecological, and environmental. Molecular studies have focused on interactions between the tick-host and pathogen/s that determine the success of pathogen acquisition by the tick and transmission to the mammalian host. In this review we draw attention to additional critical environmental factors that impact tick biology and tick-pathogen interactions. With a focus on B. burgdorferi we highlight the interplay of abiotic factors such as temperature and humidity as well as biotic factors such as environmental microbiota that ticks are exposed to during their on- and off-host phases on tick, and infection prevalence. A molecular understanding of this ensemble of interactions will be essential to gain new insights into the biology of tick-pathogen interactions and to develop new approaches to control ticks and tick transmission of B. burgdorferi, the agent of Lyme disease.

show abstract

Antiphospholipid autoantibodies in Lyme disease arise after scavenging of host phospholipids by Borrelia burgdorferi

Abstract: Conflict of interest: PJG and LTH have filed a provisional patent titled Antiphospholipid Antibodies for the Diagnosis of Lyme Disease. ARM has a patent (US 8,926,989) for an unrelated Lyme disease diagnostic.

Cited by 16 publications

References 69 publications

Annexin A2 antibodies in post-treatment Lyme disease

Annexin A2 antibodies in post-treatment Lyme disease

Croquemort elicits activation of the immune deficiency pathway in ticks

The environment, the tick, and the pathogen – It is an ensemble

Contact Info

Product

Resources

About