Evidence map›Paper›PMID 30218476›Full record

ArticleCellular microbiology2019

Robust interferon signature and suppressed tissue repair gene expression in synovial tissue from patients with postinfectious, Borrelia burgdorferi-induced Lyme arthritis.

Robert B Lochhead, Sheila L Arvikar, John M Aversa, Ruslan I Sadreyev, Klemen Strle, Allen C Steere

Open access · greenAbstract read
In one paragraph

Article in Cellular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 49 citations in OpenAlex.

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  12. Lyme Arthritis: A 50-Year Journey.The Journal of infectious diseases · 2024
    Article
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  16. Impact ofFrontiers in immunology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Robert B LochheadCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-7726-0466
Sheila L ArvikarCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
John M AversaDepartment of Orthopedics, Yale University School of Medicine, New Haven, Connecticut, USA.
Ruslan I SadreyevDepartment of Molecular Biology and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Klemen StrleCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Allen C SteereCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USYale University · US

Funding

ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTOPHER P DUGGAN · 1994 to 2026
$31.6M
Research Training in Rheumatology at Massachusetts General HospitalT32AR007258 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI ANDREW D LUSTER · 1986 to 2026
$6.9M
Borrelia burgdorferi-Induced Autoimmunity in Lyme DiseaseR01AI101175 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI STEERE, ALLEN C · 2013 to 2021
$3.6M
Cellular and humoral immunity in Lyme arthritisR01AI144365 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI STEERE, ALLEN C · 2019 to 2023
$2.9M
Defining Microbial and Host Factors in Innate Immune Responses in Lyme ArthritisK01AR062098 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI STRLE, KLEMEN · 2012 to 2014
$398k
Pathogenic and Diagnostic Implications of MicroRNAs in Lyme Disease.F32AI126764 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LOCHHEAD, ROBERT · 2016 to 2017
$59k
NIAID NIH HHS F32 AI126764NIAID NIH HHS R01 AI101175NIAID NIH HHS R01 AI144365NIAMS NIH HHS K01 AR062098NIAMS NIH HHS T32 AR007258NIDDK NIH HHS P30 DK040561
6 · The paper itself

Abstract

In most patients with Lyme arthritis (LA), antibiotic therapy results in Borrelia burgdorferi pathogen elimination, tissue repair, and return to homeostasis. However, despite spirochetal killing, some patients develop proliferative synovitis, characterised by synovial hyperplasia, inflammation, vascular damage, and fibrosis that persists for months to several years after antibiotic treatment, called postinfectious LA. In this study, we characterised the transcriptomes of postinfectious LA patients' synovial tissue, the target tissue of the immune response. High-throughput RNA sequencing to a depth of ~30 million reads per sample was used to profile gene expression in synovial tissue from 14 patients with postinfectious LA, compared with eight patients with other types of chronic inflammatory arthritis and five with minimally inflammatory osteoarthritis (OA). Synovium from postinfectious LA and other inflammatory arthritides shared gene signatures associated with antigen presentation, innate immune responses, and cell-mediated immune activation, whereas these responses were diminished in OA synovium. Unique to postinfectious LA was a particularly robust interferon-gamma (IFNγ) signature. Moreover, this heightened IFNγ signature inversely correlated with expression of genes involved in repair of damaged tissue, including genes associated with stromal cell proliferation and differentiation, neovascularisation, and extracellular matrix synthesis, which were markedly suppressed in postinfectious LA. Transcriptional observations were confirmed by cytokine profiling, histologic analyses, and clinical correlations. We propose that in patients with postinfectious LA, overexpression of IFNγ in synovium prevents appropriate repair of tissue damaged by B. burgdorferi infection, blocking return to tissue homeostasis long after completion of antibiotic therapy and resolution of active infection.

Indexed as

Adaptive ImmunityAdolescentAdultAgedAged, 80 and overBase SequenceBorrelia burgdorferiChildFemaleGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansImmunity, InnateInterferon-gammaLyme DiseaseMaleIFNG protein, humanInterferon-gamma

Identifiers

PMID30218476
PMCPMC6724218
OpenAlexW2890199122

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.