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Monday 5 sept 2022

Monday 05 Sep

07:30

Registration

New and Hot

Chairs: Hein Sprong and Joppe Hovius (Netherlands)

08:50

Short introduction chairs

Hein Sprong and Joppe Hovius (Netherlands)

09:00

What's new in Lyme diagnostics?

John Branda (USA)

09:20

New directions of therapy of tick-borne encephalitis

Daniel Ruzek (Czech Republic)

09:40

Selected abstract

10:00

Selected abstract

10:20

Break

Epidemiology (with attention for differences USA vs EU)

Chair: Paul Mead (USA)

10:50

Short introduction chair

Paul Mead (USA)

11:00

Rising incidence of tick-borne diseases in Europe?

Kees van den Wijngaard (Netherlands)

11:30

Selected abstract

11:50

Selected abstract

Poster Pitches

12:30

Lunch & Posters

Clinical and treatment

Chair: Franc Strle (Slovenia)

14:30

Short introduction chair

Franc Strle (Slovenia)

14:40

Lyme disease; from acute disease to persisting symptoms

Gary Wormser (USA)

15:10

Selected abstract

15:30

Selected abstract

15:40

Selected abstract

16:00

Break

Young & Wild: Early carreer researchers’ presentations

Chairs: Allen Steere (USA) & Gerold Stanek (Austria)

16:30

Short introduction chairs

Allen Steere (USA) & Gerold Stanek (Austria)

Introduction and Aims. Fibroblast-like synoviocytes (FLS) are critically important cells in post-infectious Lyme arthritis (LA) and in other chronic inflammatory arthritides. In inflamed tissue, FLS upregulate cell-surface expression of antigen-presenting molecules, especially HLA-DR molecules. However, little is known about the antigens presented by these cells. To better understand disease pathogenesis, we identified T cell epitopes of FLS-derived extracellular matrix (ECM) proteins, determined Borreliella (Borrelia) burgdorferi (Bb)-mimic epitopes, and characterized T and B cell responses to these peptides or proteins.

Methods. HLA-DR-presented peptides (T cell epitopes) of FLS-derived ECM proteins were identified directly from synovia of post-infectious LA patients using mass spectrometry. T and B cell responses to these proteins were determined by ELISpot and ELISA assays. Bb-mimic epitopes were identified by BLAST searches and tested for immunogenicity. Tetramer reagents were used to test directly the binding of these epitopes to patients’ CD4+ T cells and to determine the subtypes of these cells.

Results. Using immunopeptidomics to examine LA patients’ synovial tissue, we identified 3 HLA-DR-presented peptides (T cell epitopes) of fibroblast-derived ECM proteins – fibronectin-1, laminin B2, and collagen Va1. When tested for immunogenicity, 14 of 24 patients (58%) with post-infectious LA had CD4+ T cell responses to >1 of these T cell epitopes, and 9 of 52 (17%) had antibody responses to >1 of these proteins. These responses were found almost exclusively in patients with post-infectious LA, the period when massive FLS proliferation develops. Post-infectious LA patients with these T cell responses had significantly increased frequencies of HLA-DRB1*04 or DRB1*1501 alleles compared with antibiotic-responsive LA patients (P=0.0003), and among post-infectious LA patients, the duration of arthritis in the post-infectious period was significantly longer among those who had responses to FLS-derived protein epitopes compared with those who lacked these responses (P=0.05)  Of the 8 patients who had T cell reactivity with the collagen Va11730-1750 epitope, 5 also had responses to a similar Bb-mimic epitope in a previously unrecognized BBQ62-like protein, which is encoded on lp28-2. Tetramer reagents bound the autoreactive or Bb-mimic epitope, and a small percentage of cells bound both the borrelial and collagen epitopes. A high percentage of autoreactive CD4+ T cells to this one collagen epitope were T-bet-positive Th1 cells, intermediate percentages were GATA-2-positive Th2 cells or RoRgt-positive Th17 cells, and only a small percentage were FoxP3-expressing Treg cells.

Conclusion. These findings offer new insights into the pathogenesis of post-infectious LA. We propose a hypothesis linking 1) infection of collagen in joints with markedly inflammatory Bb strains, 2) induction of hyperinflammatory responses and marked proliferation of FLS, and 3) molecular mimicry between borrelial and collagen epitopes leading to collagen-reactive CD4+ T cells, which likely play a role, in part, in prolonging joint inflammation in post-infectious LA.

16:40

Selected abstract

17:00

Selected abstract

17:20

Selected abstract

17:40

Closing