Sat0030 a Novel Association Between Anti-Carbamylated Antibodies and Interstitial Lung Disease in Patients With Rheumatoid Arthritis

Abstract

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-ILDn:37Non-ILD RAn:142p valueFemale (%)25 (68)116 (82)NSAge mean (±SD)67.3 (10.1)57.7 (12.9)<0.005Mean disease duration (±SD)11.6 (7.1)5.3 (13.3)<0.005Ever smokers (%)21 (57)62 (44)NSSmoking cumulative dose (±SD)30.7 (11.1)21.8 (12)<0.005Caucasian (%)31 (84)120 (85)NSTreatmentGlucocorticoids (%)25 (68)81 (57)NScsDMARDs (%)33 (89)132 (86)NSMTX (%)20 (54)95 (67)NSbDMARDs (%)11 (30)36 (25)NSMean DAS28 (±SD)3.71 (1.35)2.74 (1.05)<0.005Erosive disease (%)26 (70)63 (44)<0.005Mean HAQ-DI (CI-95%)0.69 (0.53-0.85)0.31 (0.24-0.38)<0.005ACPA positive (%)29 (78)99 (70)NSMedian titer ACPA (IQR) CU674 (2,215)143 (1,132)NSRF positive (%)28 (76)83 (59)NSMedian titer RF (IQR) IU105 (298)34 (110)NSConclusion: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

Patient-level factors predictive of interstitial lung disease in rheumatoid arthritis: a systematic review

“…The remaining studies mostly reported varying degrees of association between RF and/or ACPA positivity and RA-ILD. [30][31][32][33][34][35][36][37] Most of these analyses were not adjusted for baseline factors and had low patient numbers, so the quality of evidence was considered to be low for the purposes of the current study.…”