Brief report: Assessment of mucosal barrier integrity using serological biomarkers in preclinical stages of rheumatoid arthritis

Benoît Thomas P Gilbert; Céline Lamacchia; Lena Amend; Till Strowig; Emiliana Rodriguez; Gaby Palmer; Axel Finckh

doi:10.3389/fimmu.2023.1117742

Brief report: Assessment of mucosal barrier integrity using serological biomarkers in preclinical stages of rheumatoid arthritis

Front Immunol. 2023 Feb 16:14:1117742. doi: 10.3389/fimmu.2023.1117742. eCollection 2023.

Authors

Benoît Thomas P Gilbert^{1

2}, Céline Lamacchia^{1

2}, Lena Amend³, Till Strowig^{3

4

5}, Emiliana Rodriguez^{1

2

6}, Gaby Palmer^{1

2

6}, Axel Finckh^{1

2}

Affiliations

¹ Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
² Geneva Centre for Inflammation Research (GCIR), Faculty of Medicine, University of Geneva, Geneva, Switzerland.
³ Department of Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.
⁴ Cluster of Excellence Resolving Infection Susceptibility (RESIST) (EXC 2155), Hannover Medical School, Hannover, Germany.
⁵ Center for Individualized Infection Medicine (CiiM), Hannover, Germany.
⁶ Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Abstract

Background: The pathogenesis of rheumatoid arthritis (RA) is believed to initiate at mucosal sites. The so-called 'mucosal origin hypothesis of RA' postulates an increased intestinal permeability before disease onset. Several biomarkers, including lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP), have been proposed to reflect gut mucosa permeability and integrity, while serum calprotectin is a new inflammation marker proposed in RA.

Methods: We analyzed serum samples of individuals genetically at increased risk of RA in a nested-case-control study. Participants from a longitudinal cohort of first-degree relatives of RA patients (SCREEN-RA cohort) were divided into three pre-clinical stages of RA, based on the presence of risk factors for subsequent RA onset: 1) low-risk healthy asymptomatic controls; 2) intermediate-risk individuals without symptoms, but with RA-associated auto-immunity; 3) high-risk individuals with clinically suspect arthralgias. Five patients with newly diagnosed RA were also sampled. Serum LBP, I-FABP and calprotectin were measured using commercially available ELISA kits.

Results: We included 180 individuals genetically at increased risk for RA: 84 asymptomatic controls, 53 individuals with RA-associated autoimmunity and 38 high risk individuals. Serum LBP, I-FAPB or calprotectin concentrations did not differ between individuals in different pre-clinical stages of RA.

Conclusion: Based on the serum biomarkers LBP, I-FABP and calprotectin, we could not detect any evidence for intestinal injury in pre-clinical stages of RA.

Keywords: autoimmunity; biomarker; gut permeability; intestinal inflammation; rheumatoid arthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid*
Biomarkers
Case-Control Studies
Humans
Leukocyte L1 Antigen Complex
Risk Factors

Substances

Biomarkers
Leukocyte L1 Antigen Complex

Grants and funding

This work is part of a research effort supported by the Swiss National Fundation for Science (SNFS), grant number 320030_192471, “Digestive Microbiome in the development of rheumatoid arthritis”. TS was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 “RESIST” – Project ID 39087428.