Immunology Department, Centre de Diagnostic Biomèdic (CDB), Hospital Clinic de Barcelona, University of Barcelona Barcelona, Spain
Albert Pérez-Isidro1, Raul Castellanos-Moreira1, Juan Camilo Sarmiento-Monroy2, Noemi de Moner1, Maresa Grundhuber3, Odette Vinas1, Raimon Sanmarti2 and Estibaliz Ruiz-Ortiz1, 1Hospital Clinic of Barcelona, Barcelona, Spain, 2Hospital Clínic de Barcelona, Barcelona, Spain, 3Thermo Fisher Scientific, Freiburg, Germany
Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation. RA-associated interstitial lung disease (ILD) is the most frequent and severe extra-articular manifestation and is associated with an increase of mortality. Rheumatoid Factor (RF-IgM) and anti-citrullinated peptide antibodies (ACPA-IgG) are important diagnostic tools included in the classification criteria (ACR/EULAR 2010). However, new biomarkers are still needed, to diagnose and predict patient's disease subsets and prognosis.
The aim of this study was to analyse the prevalence and the association with RA-ILD of non-criteria isotypes of RF, ACPA and anti-hnRNP-A2/B1 (RA33) in Hospital-Clínic Arthritis-Unit RA cohort.
Methods: This cross-sectional study included 229 patients with definite RA (ACR/EULAR 2010 criteria). ILD was diagnosed after clinical suspicion and confirmed by high resolution computed tomography. Serum samples from all RA patients and 50 healthy controls were tested for IgM/IgG/IgA of RF, ACPA (CCP2 antigen) and RA33 using EliA™ Platform (Thermo Fisher Scientific, Phadia AB, Sweden). Cut-off values were established with 95%-specificity for healthy controls.
Results: ILD was confirmed in 57 patients (RA-ILD). IgA isotype for ACPA (OR: 2.1 [1.1-4.0]), IgA-RF (OR: 2.8 [1.2-6.5]), as well as IgG-RF (OR: 2.8 [1.5-5.3]) were associated with ILD in RA.
Combinations of non-criteria autoantibodies showed a wide sensitivity (70.2% - 36.8%) and specificity (84.3% - 50.0%) range for ILD in RA. Particularly, IgA-ACPA + IgA-RF + IgG-RF showed 52.6% sensitivity and 74.4% specificity.
Conclusion: This study confirms the association of IgA-ACPA antibodies with RA-ILD, but no association with IgG-ACPA was observed. Moreover, both IgA-RF and IgG-RF are associated with RA-ILD. The results of the present study support the role of mucosal immunity in the development of ILD in patients with RA. Combinations of non-criteria autoantibodies could be useful to identify RA-ILD patients.
More prospective studies to confirm the non-criteria autoantibodies predictive value for RA-ILD stratification are warranted.
Disclosures: A. Pérez-Isidro, Thermo Fisher Scientific; R. Castellanos-Moreira, Thermo Fisher Scientific; J. Sarmiento-Monroy, None; N. de Moner, Thermo Fisher Scientific; M. Grundhuber, Thermo Fisher Scientific; O. Vinas, Thermo Fisher Scientific; R. Sanmarti, Thermo Fisher Scientific; E. Ruiz-Ortiz, Thermo Fisher Scientific.