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Abstract Number: 0051

Impact of Tight Junction Proteins on Inflammatory Processes and Microbial Imbalance in Rheumatoid Arthritis

Arkaitz Mucientes1, jose Manuel Lisbona-Montañez2, Patricia Ruiz-Limón3, Sara Manrique-Arija4, Aimara García-Studer4, Fernando Ortiz-Márquez4, Natalia Mena Vázquez5 and Antonio Fernández-Nebro6, 1IBIMA Plataforma BIONAND, Malaga, Andalucia, Spain, 2University of Malaga, Malaga, Andalucia, Spain, 3IBIMA, Instituto de Biomedicina de Málaga, Cordoba, Spain, 4Biomedical Research Institute of Malaga (IBIMA)-Bionand Platform, Department of Rheumatology, Regional University Hospital of Malaga, Malaga, Spain, 5IBIMA, Málaga, Andalucia, Spain, 6Department of Rheumatology, Hospital Universitario de Málaga, Málaga, Andalucia, Spain

Meeting: ACR Convergence 2024

Keywords: Biomarkers, C-reactive protein (CRP), Inflammation, microbiome, rheumatoid arthritis

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Session Information

Date: Saturday, November 16, 2024

Title: RA – Etiology & Pathogenesis Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: The etiology of Rheumatoid Arthritis (RA) is not fully understood. Recent studies point to intestinal permeability as an important factor in the establishment and development of RA. Tight junction (TJ) proteins play a major role in intestinal homeostasis. The alteration of this homeostasis has been related to RA. Furthermore, RA patients present dysbiosis and a lower microbiota diversity compared to healthy individuals. However, the data regarding the underlying mechanisms of the intestinal permeability-gut microbiota-tight junction proteins-RA axis are lacking.

Purpose: To quantify the TJ proteins in feces of both RA patients and healthy controls, study the relation between TJ proteins concentration and gut microbiota, and identify potential biomarkers of RA.

 

Methods: A cross-sectional study including RA patients (ACR/EULAR 2010 criteria) and sex- and aged-matched healthy controls. The quantification of TJ proteins was carried out by ELISA; specific commercial kits were used (Occludin, CSB-EL016263HU, Cusabio; Claudin-1, CSBEK005490HU, Cusabio; and Zonulin, CSB-EQ027649HU, Cusabio). Gut microbiota was evaluated by NGS platform Ion Torrent S5 and the obtained sequences were processed by Quantitative Insights Into Microbial Ecology 2 software. The inflammatory variables analyzed were DAS28-ESR, CRP, inflammatory cytokines (IL-6, IL-1, TNF-α) and oxidized LDL. Descriptive analysis, Pearson’s χ2 test, t-test or Wilcoxon test, Pearson correlation coefficient, and multiple linear regression were carried out.

Results: A total of 164 individuals were included in the study: 82 RA patients and 82 healthy controls. Table 1 shows the main clinical and demographic characteristic: 76.8% were women with an average age of 56.3±11.1 years. RA patients presented an average DAS28-ESR value of 3.0, average CRP of 3.4 mg/L and 35.4% of them were classified as obese. Only claudin-1 showed significant differences (RAmean: 19.8±13.7pg/mL vs. Controlmean: 26.8±17.3pg/mL, p=0.024) (Figure 1). Results evidenced a correlation between claudin-1 values and both age (Spearman’s rho: -0.317; p< 0.05) and BMI (Spearman’s rho: 0.326; p< 0.05), and between zonulin values and both CRP (Spearman’s rho: 0.326; p< 0.05) and TNFα (Spearman’s rho: 0.326; p< 0.05). Multivariant analysis (Table 2 and 3) showed that claudin-1 and CRP levels are related in RA patients (β: -0.619; p: 0.045), and subgroup of patients with RA who had not achieved clinical remission the abundance of genus Veillonella is positively associated with claudin-1 levels (β: 39.000; p: 0.004).

Conclusion: RA patients are likely to show altered intestinal permeability compared to healthy controls due to decreasing claudin-1 levels. Moreover, CRP levels are inversely associated with claudin-1 levels, which suggests a possible role of inflammation in claudin-1 regulation in RA. In addition, TJ proteins in stool are correlated with RA clinical parameters, supporting a potential use as biomarkers in RA context. Finally, our results suggest that claudin-1 could be a cause of the dysbiosis observed in RA patients.

Supporting image 1

Table 1. Clinical and demographic characteristics of the cohort.

Supporting image 2

Figure 1 – Concentration of the tight junction proteins analysed in feces.
Red: RA patients; blue: healthy controls. Data are shown as mean ± standard deviation for claudin_1, and median (p25-p75) for occludin and zonulin. Significance level: p≤0.05

Supporting image 3

Linear regression model results.


Disclosures: A. Mucientes: None; j. Lisbona-Montañez: None; P. Ruiz-Limón: None; S. Manrique-Arija: None; A. García-Studer: None; F. Ortiz-Márquez: None; N. Mena Vázquez: None; A. Fernández-Nebro: Argenx, 5, AstraZeneca, 2, 5, Chemo, 5, Eli Lilly, 2, Galapagos, 2, 5, Gebro Pharma, 2, GlaxoSmithKlein (GSK), 6, GSK, 2, Janssen, 5, Merck Serono, 5, MSD, 5, Novartis, 2, 5, Takeda, 5, UCB, 5.

To cite this abstract in AMA style:

Mucientes A, Lisbona-Montañez j, Ruiz-Limón P, Manrique-Arija S, García-Studer A, Ortiz-Márquez F, Mena Vázquez N, Fernández-Nebro A. Impact of Tight Junction Proteins on Inflammatory Processes and Microbial Imbalance in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/impact-of-tight-junction-proteins-on-inflammatory-processes-and-microbial-imbalance-in-rheumatoid-arthritis/. Accessed .
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