Anti-cyclic citrullinated peptide (CCP) antibody in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) without rheumatoid arthritis

Abstract

Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group (p = 0.03) and controls (p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls.

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.…”

Lung alveolar tissue destruction and protein citrullination in diesel exhaust‐exposed mouse lungs

“…PAD 2 and 4 are particularly well‐known inflammatory deiminases . Citrullination in lungs is associated with tobacco smoking, air pollution and other toxic exposures . In sum, inhaled air pollution compounds are associated with the up‐regulation of local citrullination in the lungs rendering proteins immunogenic …”

“…30 Post-translational citrullination is implicated in initiation of autoantibody formation, autoimmunity and subsequent development of rheumatoid arthritis and other autoimmune diseases. 31,32 Peptidyl-arginine deiminases (PADs) are responsible for citrullination and conversion of positively charged arginine into neutral, potentially immunogenic citrulline, 34,35 affecting protein-protein interactions, hydrogen bond formation, protein structure and denaturation. Under the physiological conditions, PADs are inactive due to the low calcium levels.…”

“…32,37 Citrullination in lungs is associated with tobacco smoking, air pollution and other toxic exposures. 31,32,34 In sum, inhaled air pollution compounds are associated with the up-regulation of local citrullination in the lungs rendering proteins immunogenic. 38 Phytocannabinoids, like cannabidiol (CBD), have been widely studied as candidate therapeutics.…”

Health status assessment in COPD

“…The MCID is defined as "the smallest difference in a measurable clinical parameter that indicates a meaningful change in the condition for better or for worse, as perceived by the patient, clinician or investigator" (70). A MCID is also frequently used to perform a sample size calculation, assess the efficacy of specific therapies and to assist in interpreting statistical significant results (71,72).…”