A PREDOMINANT NON-SPECIFIC INTERSTITIAL PNEUMONIA PATTERN AND ABERRANT TRANSCRIPTOMIC NEUTROPHIL-MEDIATED IMMUNITY CHARACTERIZE A CONTEMPORARY RA-ILD COHORT

BackgroundLung involvement is the most common extra-articular manifestation. Rheumatoid arthritis related interstitial lung disease (RA-ILD) comprises a heterogeneous group of parenchymal lung disorders classified by distinct clinical, pathologic, and radiographic features. According to the current paradigm, circulating immune complexes and aberrant neutrophil extracellular trap formation (NETosis) contribute to disease pathogenesis.ObjectivesTo characterize the pattern of lung disease in “Attikon” RA-ILD cohort and develop insights about the pathophysiologic mechanisms via whole blood RNA sequencing.MethodsRetrospective and prospective study to identify clinical, laboratory and radiologic characteristics of patients with RA and pulmonary manifestations in the “Attikon” RA-ILD cohort. Changes in pulmonary function tests (PFTs), pattern of lung involvement (chest HRCT), disease activity (DAS28-ESR) and incidence of complications and comorbidities, were prospectively analyzed during the one-year follow-up period. Peripheral blood was collected in a subset of RA-ILD (n=11) and control RA patients (n=9) for RNA isolation and RNA sequencing. The gene expression profile of RA-ILD was inferred through differential gene expression analysis, followed by pathway and enrichment analyses.Results114 patients with RA-ILD were included [67% female, mean (SD) age at diagnosis 71.5 (9) years, 58% seropositive]. Non-specific interstitial pneumonia (NSIP) was the radiologic pattern most frequently observed (52%), followed by usual interstitial pneumonia (UIP) (24%). RA was diagnosed after ILD in 40% of patients. Mean (SD) FVC and DLCOsb at baseline was 80.5 (19.2) and 55.4 (19.5), respectively. Disease activity was lower in seropositive compared to seronegative both at baseline and at 1-year follow-up (p=0.025). PFTs at 12 months from baseline had been stabilized. Respiratory infections were observed in 17.6% of patients during the first year of follow-up, more common in the NSIP vs UIP group (p=0.01), possibly due to the higher doses of glucocorticoids in NSIP patients. RNA-sequencing analysis revealed a distinct gene expression profile in RA-ILD, characterized by the activation of type I interferon response, neutrophil activation and degranulation, and CCR1 chemokine interactions.ConclusionNSIP is the most frequent pattern of ILD in this RA-ILD cohort, carrying a higher risk for respiratory infections probably related to higher doses of glucocorticoid used. Myeloid cells’ migration via CCR1 and the formation of pro-inflammatory and pro-fibrotic NETs by activated neutrophils may contribute to RA-ILD pathogenesis.References[1]Y Dai et al, Rheumatoid arthritis–associated interstitial lung disease: an overview of epidemiology, pathogenesis and management Clin Rheumatol. 2021 Apr;40(4):1211-1220[2]X Zulma Yunt et al, Lung Disease in Rheumatoid Arthritis Rheum Dis Clin North Am. 2015 May;41(2):225-36Table 1.Patients’ characteristics with RA-ILD in Attikon cohortPatients CharacteristicsN=114Mean age71.5±9Female: Male76/38Smoking (current/ex)23/43Arterial hypertension71Diabetes mellitus32Dyslipidemia52COPD/BA17Thyroid disease30Latent TB17Seropositive66Diagnosis RA before ILD34Diagnosis RA after ILD45NSIP59UIP27Mixed NSIP-UIP5Organizing Pneumonia (OP)17Nodules21Disclosure of InterestsNone declared