Pos1016 analysis of gut microbiota in rheumatoid arthritis-associated interstitial lung disease

Background The gut microbiota has been related to rheumatoid arthritis (RA), inflammation, and its severity. Interstitial lung disease (ILD) causes high morbidity and mortality in RA patients. However, the association between gut microbiota and RA- associated ILD (RA-ILD) is still unknown. Objectives -To analyze the gut microbiota and gut permeability in RA-ILD patients. -To evaluate the association between gut microbiota and permeability, and the pulmonary progression. Methods Nested case-cohort study of 2 prospective cohorts of patients with RA with and without ILD. The cohorts were matched for age, sex, and time of RA evolution. All cases systematically underwent high-resolution computed tomography (HRCT) and pulmonary function testing (PFT) on the diagnosis of ILD. The ILD was defined according to the lung biopsy or HRCT based on the standard criteria of the American Thoracic Society/European Respiratory Society, the progression was defined as the worsening of the FVC > 10% or DLCO > 15%. The gut microbiota was measured by the 16S rRNA gene and the sequences were processed using the Quantitative Insights into Microbial Ecology (QIIME2). Serum lipopolysaccharide-binding protein (LBP) and lipopolysaccharide (LPS) were measured as markers of gut permeability. Demographic, clinical, laboratory, and treatment-related data were recorded. The disease activity was measured by Disease Activity Score-28 with Erythrocyte Sedimentation Rate (DAS28-ESR), and the function using the Health Assessment Questionnaire (HAQ). We performed a descriptive analysis and Cox regression analysis to identify prognostic factors for the time to progression of RA-ILD. Results Thirty-five RA-ILD and 35 RA without ILD were included. Table 1 shows the baseline characteristics. After a median (SD) period of 66,1 (47,2) months, pulmonary progression criteria had observed in 13 patients (37.1%). Compared with controls, RA-ILD had greater values of DAS28-ESR (p=0.032) and higher HAQ scores (p=0.003). They also had higher levels of serum LPS (p = 0.007) and more abundance of Streptococcus genus (p = 0.087), as well as a lower abundance of Slackia (p = 0.022) and Paraprevotella genera (p = 0.082 ). The RA-ILD with progression had a higher abundance of Streptococcus genus (p = 0.090) and a lower abundance of Slackia genus. In Cox regression analysis, the moderate-high activity of DAS28-ESR (HR [IC 95%], 3.53 [1.20-6.98]; p=0.017), LPS (HR [IC 95%], 1.12 [1.02-1.23]; p=0.018) and the Slackia genus (HR [IC 95%], 0.98 [0.97-0.99]; p=0.010) were associated with RA-ILD. Conclusion RA-ILD patients showed increased gut permeability and also displayed a different pattern of gut microbiota associated with ILD diagnosis and prognosis. These findings may enable the discovery of potential RA-ILD biomarkers. Table 1. Clinical and demographic characteristics VARIABLE RA-ILD n=35 RA without ILD n=35 P-value Age in years, mean (SD) 69.7 (9.3) 66.6 (7.0) 0.130 Male; n (%) 20 (57.1) 20 (57.1) 1.000 Smoking 0.760 Never smoked, n (%) 17 (48.6) 18 (51.4) Ex-smoker, n (%) 10 (28.6) 8 (22.9) Active smoker, n (%) 8 (22.9) 9 (25.7) Time since diagnosis RA, months, median (IQR) 149.8 (93.3-245.5) 133.7 (67.8-204.2) 0.384 Time since diagnosis of ILD, mean (SD) 66.1 (47.2) - - RF+ (>10), n (%) 33 (94.3) 31 (88.6) 0.393 ACPA+ (>20), n (%) 32 (91.4) 31 (88.6) 0.690 Erosions, n (%) 21 (60.0) 19 (55.6) 0.705 DAS28-ESR, mean (SD) 3.1 (0.9) 2.6 (0.9) 0.032 HAQ, mean (SD) 1.2 (0.6) 0.8 (0.6) 0.003 FVC mean (SD) 63.0 (17.1) 83.4 (4.4) <0.001 DLCO, mean (SD) 61.0 (15.2) 85.9 (7.9) <0.001 UIP, n (%) 29 (82.9) 0 (0.0) <0.001 NSIP, n (%) 6 (17.1) 0 (0.0) <0.001 Abbreviations. ACPA: anticitrullinated peptide antibody; DAS28: Disease activity score; DLCO: diffusing capacity of the lung for carbon monoxide; ESR: erythrocyte sedimentation rate; FVC: forced vital capacity; HAQ: Health Assessment Questionnaire; IQR: interquartile range; NSIP: nonspecific interstitial pneumonia; RA: rheumatoid arthritis; RF: rheumatoid factor; SD: standard deviation; UIP: usual interstitial pneumonia. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.