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.

The authors of this article, led by GCIR Professor Axel Finckh, 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.

The study 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.

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

Full article: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117742/full 

Why is it important?

Rheumatoid arthritis (RA) is an auto-immune disease leading to joint destruction and extra-articular manifestations. Researchers have hypothesized that RA autoimmunity is initially triggered at the mucosal level, for instance in the oral cavity or gastro-intestinal tract. Assessing gut mucosal barrier integrity in individuals at risk of RA would be important since targeting the intestinal barrier function by dietary changes might provide an opportunity to modulate the development of RA.

The authors of this article analysed, in a cohort of patients genetically at increased risk of RA, two biomarkers that have been proposed to reflect gut mucosa permeability and integrity, and one new inflammation marker proposed in RA. Contrary to previous mice-derived evidence, the authors found no association between putative serum biomarkers of intestinal integrity and preclinical stages of RA development. Future research needs to clarify if these makers truly signal changes in intestinal integrity or instead merely reflect systemic inflammation.