A NOVEL ASSOCIATION BETWEEN ANTI-CARBAMYLATED ANTIBODIES AND INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Interstitial lung disease (ILD) is associated with a significant increase in morbidity and mortality in patients with rheumatoid arthritis (RA). Therefore, an early diagnosis is fundamental. Anti-carbamylated proteins (Anti-CarP) have been described in different chronic respiratory diseases without a previous history of RA. Objectives: The aim of this study was to analyse the association between Anti-CarP and ILD in RA patients. Methods: We performed a cross-sectional study, including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised 2 groups: 1) RA patients diagnosed with ILD (RA-ILD group) and 2) RA patients without ILD (non-ILD RA group). ILD was diagnosed by high-resolution tomography and confirmed by a multidisciplinary committee. Three IgG Anti-CarP autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib), and fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarPs and ILD were explored using multivariable logistic regression adjusted by a set of variables known to be related to the development of ILD: smoking, sex, age, RA disease duration, RF and ACPA. An independent replication sample was obtained to validate our findings from another hospital. Results: The main population included 179 patients: 37 were included in the RA-ILD group, and 142 in the non-ILD RA group. Most patients were female (79%), with a mean age of 59.7±13 years with a mean disease duration of 6.6±5 years. Baseline features are shown in table 1 . The replication sample was composed of 25 patients in the RA-ILD group and 50 patients in the non-ILD RA group. We found that Anti-CarPs specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs. 43%; Anti-Fib 73% vs. 51%; Anti-CFFHP 38% vs. 19%; Anti-CarP-IgA 51% vs. 20%, p<0.05 for all comparisons). Serum mean titers of Anti-CarPs were higher in RA-ILD patients with significant statistical differences for all of them, except Anti-Fib. The multivariate analysis showed that Anti-CarPs specificities were independently associated with ILD (Anti-FCS (OR: 3.42; CI95%: 1.13-10.40), Anti-Fib (OR: 2.85; CI95%: 0.83-9.70), Anti-CFFHP (OR: 3.11; CI95%: 1.06-9.14) and Anti-FCS-IgA (OR: 4.30; CI95%: 1.41-13.04). In the replication sample our findings were validated only for Anti-FCS (OR: 10.42; CI95%: 1.68-64.46). TABLE 1. Main population demographic, clinical, therapeutic, and autoantibody status features. RA-ILD n:37 Non-ILD RA n:142 p value Female (%) 25 (68) 116 (82) NS Age mean (±SD) 67.3 (10.1) 57.7 (12.9) <0.005 Mean disease duration (±SD) 11.6 (7.1) 5.3 (13.3) <0.005 Ever smokers (%) 21 (57) 62 (44) NS Smoking cumulative dose (±SD) 30.7 (11.1) 21.8 (12) <0.005 Caucasian (%) 31 (84) 120 (85) NS Treatment Glucocorticoids (%) 25 (68) 81 (57) NS csDMARDs (%) 33 (89) 132 (86) NS MTX (%) 20 (54) 95 (67) NS bDMARDs (%) 11 (30) 36 (25) NS Mean DAS28 (±SD) 3.71 (1.35) 2.74 (1.05) <0.005 Erosive disease (%) 26 (70) 63 (44) <0.005 Mean HAQ-DI (CI-95%) 0.69 (0.53-0.85) 0.31 (0.24-0.38) <0.005 ACPA positive (%) 29 (78) 99 (70) NS Median titer ACPA (IQR) CU 674 (2,215) 143 (1,132) NS RF positive (%) 28 (76) 83 (59) NS Median titer RF (IQR) IU 105 (298) 34 (110) NS Conclusion: A strong association between RA-ILD and Anti-CarP was found independently of cofounders, including RF and ACPA. Our findings suggest a possible link between Anti-CarP and the development of ILD. Disclosure of Interests: Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Sebastian Rodriguez-Garcia: None declared, Katherine Cajiao: None declared, Gabriela Jimenez: None declared, Maria Jose Gomara: None declared, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Ivette Casafont-Solé: None declared, Julio Ramirez: None declared, José Gomez Puerta Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Susana Holgado Pérez: None declared, Juan de Dios Cañete: None declared, Isabel Haro: None declared, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 940Session: Rheumatoid arthritis - prognosis, predictors and outcome (Poster Presentations)