Role of mucosal antigens for the pathogenesis of Spondyloarthritis (SpA)

Concept

This project aims to improve the understanding of what causes and stimulates inflammation in SpA patients. Specifically, the project tests the hypothesis that the barrier function of the gut is impaired in SpA patients, which could promote the entry of bacterial components from the gut into the body. Such bacterial components can activate directly or indirectly pathogenic immune responses.

Facts and figures

Project lead
U Syrbe
Charité
Uta.Syrbe@charite.de
FOREUM research grant: € 300.000
2017–2020

Meet the team

U Syrbe
Charité
M Breban
Université Versailles Saint-Quentin
P Jacques
University Hospital Gent
D Elewaut
Center for Inflammation Research

Patient voice

In the project patient-reported disease activity scores, patient reported functional scores as well as the patient acceptable symptom state (PASS) score are included to determine relations of translocation biomarkers to these patient reported outcome parameters.

Final results

The project started in Feb 2017.

Soluble biomarkers indicative of  bacterial translocation  in SpA

  • lipopolyaccharide binding protein (LBP) is upregulated in axial SpA patients compa- red to controls.
  • there is no difference according to disease state ( i.e. nr-axial SpA and AS) and disease activity (i.e. BASDAIhigh and BASDAI low).
  • In patients from GIANT cohort (Belgium) LBP serum levels were significantly higher in patients with chronic gut inflammation compared to patients without gut inflammation.

Cellular Biomarkers

In transcriptome analysis of CD14+ monocy- tes 957 Affymetrix probe sets were differen- tially expressed between axSpA patients and HC (Berlin). Coexpression analysis with refe- rence transcriptomes found an overlap of these IDs with late myeolopoesis and responses trigged by G-CFS mobilization and by LPS and TNF suggesting changes in myelopoiesis.

Mechanism of translocation in HLA-B27 tg rats

  • HLAB27tg rats spontaneously develop coli- tis as indicted by infiltration of CD3+ T cells.
  • mRNA expression data of colon epithelial cells suggest dysregulation of tight junction molecules in HLA-B27tg rats. These differences could not be verified on protein level suggesting that translocation may occur despite unimpaired expression of tight junction molecules

Abstracts EULAR 2019

FRI0360: Analysis of blood monocyte transcriptomes and bone marrow samples of patients with Axial Spondyloarthritis reveals their changes related to activation and Myelopoesis