Anti-CarP May Play Special Role in RA-Associated Mortality

Although rheumatoid arthritis (RA) primarily affects joints, its extra-articular manifestations include the lungs, blood vessels and skin. Physicians not only use these physical manifestations to describe patients, but also to characterize them on the basis of the presence of RA-specific autoantibodies, such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP). Recent research has established a new RA autoantibody, anti-carbamylated protein (anti-CarP) antibodies.

Numerous studies have investigated the role of these autoantibodies in disease outcomes. This research has revealed that patients with RA who have RA-specific autoantibodies, such as RF and anti-CCP, have an increased mortality rate. Unfortunately, although investigators have studied the relative role these autoantibodies (particularly RF and anti-CCP) play in increasing mortality risk, the data from published studies are contradictory.

New results now suggest that a specific relationship between anti-CarP antibodies and increased mortality in patients with RA may exist. Laura Vidal-Bralo and colleagues at the Hospital Clinico Universitario de Santiago in Spain propose in their latest study, published online in PLoS One, that there may be a connection between anti-CarP antibodies and respiratory diseases. Their suggestion is noteworthy because few studies have addressed the association of RA autoantibodies and specific causes of death. However, the authors note that this question is important, because it may yield answers that may help to elucidate the mechanisms leading to increased mortality in patients with RA, as well as suggest biomarkers that can help identify patients at increased risk.¹

In the study, the researchers describe their evaluation of 331 patients with established RA—124 of whom died. The patients were recruited from 2001 to 2009 from the Spanish outpatient rheumatology clinic based on fulfillment of the ACR classification criteria. Investigators collected survival data until November 2015.

The death rate in the study corresponded with a mortality rate of 1.53 (95% confidence interval of 1.26 to 1.80) relative to the reference population. The univariate analysis identified known risk factors that are associated with increased mortality: old age, smoking and being male. The investigators then performed a multivariate analysis that included all autoantibodies. This analysis revealed a marked increase in the hazard ratios (HRs) of RF and anti-CCP antibodies that was not statistically significant. In contrast, the HR of anti-CarP showed a significant association with decreased survival that was on the same order of magnitude as smoking’s association with mortality.

The research revealed that not only was anti-CarP the only significant association among the autoantibodies, but the association was specific for a respiratory system cause of death. They concluded this based on the fact that the HR for diseases of the respiratory system was significantly higher than the HR for all-cause mortality. The classification of diseases of the respiratory system included pneumonias and other respiratory infections, interstitial lung diseases that could be attributed to RA and respiratory insufficiencies attributed to COPD. It also includes patients coded with a disease group level corresponding to the J00-J99 codes of the 10th revision of the International Classification of Diseases.