Anti-citrullinated peptide antibodies in the serum of heavy smokers without rheumatoid arthritis. A differential effect of chronic obstructive pulmonary disease?

Abstract

The objective of this study is to analyse the frequency and levels of anti-citrullinated peptide/protein antibodies (ACPA) in the serum of non-rheumatoid arthritis (RA) heavy smokers with and without chronic obstructive pulmonary disease (COPD) and compare them with healthy never smokers and patients with RA. Serum samples of 110 heavy smokers without RA, 209 healthy never smokers and 134 patients with RA were tested for ACPA using a commercial anti-cyclic citrullinated peptide antibodies (CCP2) test and a homemade chimeric fibrin/filaggrin citrullinated synthetic peptide (anti-CFFCP) ELISA test. The frequency of positive results and autoantibody levels were compared between groups. The prevalence of the two types of ACPA was slightly higher in heavy smokers than in never smokers, although the difference was not significant, and significantly lower than in RA patients. The highest prevalence of positive ACPA in heavy smokers was found in subjects with COPD (7.4% of positive anti-CFFCP in patients with COPD in comparison with 2.4% in never smokers: OR 3.26; 95% CI 0.85-12.6, p = 0.089). Mean serum levels of ACPA in heavy smokers were not significantly different from those of never smokers. Heavy smokers with COPD had significantly higher levels of anti-CFFCP than those without COPD, although almost all patients had serum levels below the cut-off values. The prevalence of ACPA in heavy smokers without RA is low, but seems to be higher in heavy smokers with COPD. Larger studies are necessary to confirm these findings and determine the relationship between ACPA and lung disease.

Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease

“…In contrast to MAA, citrulline was expressed in both RA-ILD and emphysema. Although the specificity of serum anti-CCP antibodies for RA approaches 96% (37), others have similarly found citrulline and ACPA responses to accompany chronic obstructive lung diseases in the absence of RA (38)(39)(40). Given the strong colocalization of MAA with citrullinated antigens in RA-ILD, we postulate that MAA could act as a "second hit" in RA pathogenesis by facilitating loss of tolerance to colocalized citrullinated antigens.…”

The lung may play a role in the pathogenesis of rheumatoid arthritis

“…In addition, recent studies of subjects with smoking associated chronic airways disease, specifically chronic obstructive lung disease (COPD), without joint inflammation have identified an increased prevalence of serum ACPA positivity further supporting that the lung may be a site of generation of RA-related autoimmunity [55,56]. Specifically, Ruiz-Esquide and colleagues evaluated subjects without RA who had a heavy smoking history and COPD, and in these subjects, they found a higher prevalence of serum ACPA positivity (4–7%) compared with controls without a history of smoking (2%) [56]. …”

Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis

“…While PAD activity has primarily been found to regulate autoimmune-mediated inflammatory events, recent studies suggest that PAD-mediated citrullination is also elevated in a variety of inflammatory states which lack a strong autoimmune component, such as COPD and myositis [76–78]. Perhaps the best demonstration that PAD-mediated citrullination can facilitate nonautoimmune or microbial-induced inflammatory events is the recent finding that PAD activity is strongly upregulated in inflamed tissue following a sterile skin punch biopsy procedure in mice [79].…”