Abstract

ObjectiveRheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD.MethodsSera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay.ResultsThe comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10− 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10− 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10− 11).ConclusionRF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

Highlights

  • Rheumatoid arthritis (RA), a systemic autoimmune disease affecting synovial joints, is often complicated with chronic lung diseases (CLD), including interstitial lungOka et al BMC Musculoskeletal Disorders (2022) 23:46 disease (ILD) and airway disease (AD)

  • The comparison of RA patients with and without CLD showed that rheumatoid factor (RF) immunoglobulin A (IgA) was associated with interstitial lung disease (ILD), usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × ­10− 7)

  • RF IgA and anti-citrullinated peptide antibody (ACPA) secretory component (SC) in RA were associated with UIP and nonspecific interstitial pneumonia (NSIP), respectively, suggesting different specificities in patients with RA

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Summary

Introduction

Rheumatoid arthritis (RA), a systemic autoimmune disease affecting synovial joints, is often complicated with chronic lung diseases (CLD), including interstitial lungOka et al BMC Musculoskeletal Disorders (2022) 23:46 disease (ILD) and airway disease (AD). The serum levels of RFs are linked to RA-associated ILD (RA-ILD) [6, 7]. Anti-citrullinated peptide antibodies (ACPAs) are autoantibodies against citrullinated peptides. The specificity of ACPA for RA is higher than that of RFs, and the serum levels of ACPA IgG are associated with RAILD [6, 9, 10]. The serum levels of ACPAs with secretory component (SC) have been linked to RA-ILD [12]. Anti-carbamylated protein (CarP) antibodies recognize homocitrullinated peptides generated by posttranslational modification of lysine residues. Anti-CarP antibodies were reported to be associated with ILD in RA [16]. We investigated the association of RF, ACPA, and anti-CarP antibodies with RA-ILD in Japan

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