AB0727 TIGHT JUNCTION PROTEINS IN RHEUMATOID ARTHRITIS: ETIOLOGY AND BIOMARKERS
Authors: A. Mucientes, J. M. Lisbona-Montañez, P. Ruiz-Limon, G. M. Martín-Núñez, L. Cano-Garcia, S. Manrique-Arija, N. Mena-Vázquez, A. Fernández-Nebro
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> 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 [1]. Tight junction (TJ) proteins play a major role in intestinal homeostasis, key to the proper functioning of the communication between the internal and external environment that occurs through the intestinal tract [2]. The alteration of this homeostasis has been related to RA. However, the data regarding the underlying mechanisms of the intestinal permeability-tight junction proteins-RA axis are lacking [3]. <h3>Objectives:</h3> This work aimed to quantify the TJ proteins present in feces of both RA patients and healthy controls, analyze the differences, and identify potential biomarkers for diagnosis and severity of RA. <h3>Methods:</h3> A cross-sectional study including RA patients and sex- and aged-matched healthy controls was performed. RA patients were diagnosed according to the 2010 criteria of the American College of Rheumatology/European League against Rheumatism. During visits to the rheumatologist, feces and other epidemiological, clinical-analytical variables, inflammatory and therapeutic parameters were collected. All subjects gave their informed consent for inclusion before they participated in the study. The quantification of TJ proteins present in feces was carried out by Enzyme-Linked Immuno Sorbent Assay (ELISA), specific commercial kits were used for each protein (Occludin, CSB-EL016263HU, Cusabio; Claudin, CSB-EK005490HU, Cusabio; and Zonulin, CSB-EQ027649HU, Cusabio). The inflammatory variables analyzed were disease activity Score (DAS28), C-reactive protein (CRP), inflammatory cykines (IL-6, IL-1, TNF-α) and oxidized LDL. Statistical analysis was carried out using IBM SPSS Statistics 27 software. TJ proteins values in both groups were compared by Pearson's χ2 test or t-test, as appropriate. Furthermore, it was calculated the Pearson correlation coefficient between proteins values and RA characteristics. Finally, a multiple linear regression was carried out to identify TJ protein-related factors in RA patients. <h3>Results:</h3> 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 characteristics of the cohort. 76.8% were women with an average age of 56.3±11.1 years. RA patients present an average DAS28 value of 3.0, average CRP of 3.4 mg/L and 35.4% of them were classified as obese. Figure 1 shows the quantification of the TJ proteins in both groups. Only claudin present significant differences between groups, with lower values in RA patients [RA<sub>mean</sub>: 19.8(±13.7) pg/mL; Controls<sub>mean</sub>: 26.8(±17.3) pg/mL; <i>p</i>: 0.024]. There were no significant differences regarding neither occludin [RA<sub>median</sub>: 10.0 pg/mL (8.5-17.1); Controls<sub>median</sub>: 9.8 pg/mL (8.1-12.0); <i>p</i>: 0.412] nor zonulin [RA<sub>median</sub>: 3.4 ng/mL (2.2-7.9); Controls<sub>median</sub>: 4.2 ng/mL (1.9-10.1); <i>p</i>: 0.431]. Correlation analysis evidenced a correlation between claudin values and both age (Spearman's rho: -0.317; <i>p</i>&lt;0.05) and body mass index (Spearman's rho: 0.326; <i>p</i>&lt;0.05), and between zonulin values and both CRP (Spearman's rho: 0.326; p&lt;0.05) and TNFα (Spearman's rho: 0.326; <i>p</i>&lt;0.05). Finally, multivariant analysis showed that claudin and CRP levels are significantly related (<i>β</i>: -0.619; 95CI: -1.222, -0.015; <i>p</i>: <i>0</i>.045). <h3>Conclusion:</h3> RA patients present a lower concentration of claudin than healthy controls, which compromise the intestinal homeostasis and would result in an increasing of the intestinal permeability. Furthermore, both claudin and zonulin show correlation with several clinical characteristics of RA. Taken together, our results indicate that TJ proteins are involved in the pathogenesis of the RA and could be used as biomarkers in the context of RA. Future studies are needed to validate the findings. <h3>REFERENCES:</h3> [1] Blenkinsopp <i>et al</i>. J Am Nutr Assoc, 2024. 43(1):59-76. [2] García MA <i>et al</i>. Cold Spring Harb Perspect Biol, 2018. 10(4):a029181. [3] Hecquet S <i>et al</i>. Semin Arthritis Rheum, 2021. 51(4):712-718. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>