Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis.

Brink M, Ljung L, Hansson M, Rönnelid J, Holmdahl R, Skriner K, Serre G, Klareskog L, Rantapää-Dahlqvist S

Rheumatology (Oxford) - (-) - [2022-05-09; online 2022-05-09]

Pulmonary manifestations in rheumatoid arthritis (RA) are common comorbidities but the underlying mechanisms are in large unknown. The added value of a multiplex of anti-citrullinated peptide antibodies (ACPA) and genetic risk markers were evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities were analysed using a custom-made microarray chip (Thermo-Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated rs2609255 (FAM13A), rs111521887 (TOLLIP), rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. In unadjusted analyses eleven ACPA specificities were associated with PF development. In multiple variable analyses six ACPA specificities associated with increased risk of PF; Vimentin(Vim)60-75, Fibrinogen(Fib)β62-78 (72), Fibα621-635, Bla26, Collagen(C)II359-369 and F4-CIT-R (p< 0.01-p< 0.05). The number of ACPA specificities were also related to PF development (p< 0.05 crude and adjusted models). In multiple variable models adjusted for the SNPs respectively, the number of ACPA specificities (p< 0.05 in all models), Vim60-75 (p< 0.05, in all models), Fibβ62-78 (72) (p< 0.001-p< 0.05), antiCII359-369 (p< 0.05 in all models) and F4-CIT-R (p< 0.01-p< 0.05), Fibα621-635(p< 0.05 in one) and anti-Bla26 (p< 0.05 in two) were significantly associated with PF development. The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA, and the number of ACPA specificities and risk genes.

NGI SNP genotyping [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 35532073

DOI 10.1093/rheumatology/keac280

Crossref 10.1093/rheumatology/keac280

pii: 6582550


Publications 7.2.7