PULMONARY FIBROSIS IN EARLY RHEUMATOID ARTHRITIS IN RELATION TO GENETIC LOCI AND INDIVIDUAL ACPA SPECIFICITIES

• Pulmonary manifestations in rheumatoid arthritis (RA) are common comorbidities but the underlying mechanisms are largely unknown. We found in a previous study 3 SNPs associated with pulmonary fibrosis (PF); rs35705950 (MUC5B), rs111521887 (TOLLIP), and rs2609255 (FAM13A) besides age, rheumatoid factor positivity and methotrexate treatment.ObjectivesTo evaluate for the added value of a multiplex of anti-citrullinated peptide antibodies (ACPA) for the development of pulmonary fibrosis (PF) in an inception cohort of RA patients.MethodsA total of 1184 patients with early RA were consecutively included and followed prospectively from the date of diagnosis (index date) until death or until 31 December 2016. The diagnosis of PF was based on high resolution tomography. The presence of 21 ACPA fine specificities were analysed in plasma sampled at index date, using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Data on both ACPA and genetic data was available for 841 RA patients, of whom 50 developed PF. Associations were analysed using logistic regression analysis and presented as the odds ratio (OR) with the 95% confidence interval (CI). Models were adjusted for sex, age, DAS28 and presence of RF at RA diagnosis, smoking ever, and HLA-SE and in a second step for the three SNPs (.rs35705950, rs111521887 and rs2609255), respectively.ResultsIn unadjusted analyses eight ACPA reactivities were found associated with PF development (p< 0.05-0.001). The number of ACPA reactivities was related to PF development, both in crude and adjusted models (p<0.05 for both). In models concomitantly adjusted for the three SNPs (rs35705950, rs111521887 and rs2609255) respectively, in addition to mentioned adjustments the number of ACPA reactivities (p<0.05 for all three nmodels), Vim60-75 (p<0.05, in all three models), Fibβ62–78 (72) (p<0.001-p<0.05) and F4-CIT-R (p<0.01-p<0.05) were all found significantly associated to PF development irrespective of the SNPs.ConclusionThe development of PF in an inception cohort of RA patients was associated both with risk genes and, independently of the risk genes, the presence of certain ACPA, and the number of ACPA reactivities.References[1]Jönsson E, et al. Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden. Rheumatology (Oxford). 2021 May 16:keab441. doi: 10.1093/rheumatology/keab441.AcknowledgementsI have no acknowledgements to declare. The staff and patients at the departments of rheumatology in northern Sweden.Disclosure of InterestsNone declared

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