Does ACPA Increase the Risk of Interstitial Lung Disease? Save

The anti-citrullinated peptide (anti-CCP or ACPA) antibody assay has a specificity of greater than 90% for rheumatoid arthritis and is associated with worse articular outcomes. ACPA has been shown to increase the risk and severity of rheumatoid arthritis, but it has also been variably associated with an increased risk of interstitial lung disease (ILD) that may complicate RA (Citation source http://buff.ly/1LS4T6K).

A metanalysis of 243 patients with RA-ILD and 1442 RA controls concluded that ACPA+ was associated with and increased risk of lung disease (pooled OR = 2.6). Giles and coworkers analyzed 177 RA patients and found that CCP/ACPA titers were 46-273% higher among RA patients with ILD versus those without. (Citation source http://buff.ly/1UAoEn8). Lastly, Doyle et al studied 189 RA patients and showed that CCP, RF, age, sex and smoking predicted CT-proven ILD (Citation source http://buff.ly/1UEXLyk).

Finally, at last year’s ACR meeting, Correia et al described their cohort review of 2030 patients undergoing CCP testing, 334 of whom had RA. Among all patients that were CCP positive, a progressively higher prevalence of ILD was associated with higher titers of CCP (p0.0001). However, the association was diminished when adjusting for age, C-reactive protein, tobacco use, and a diagnosis of RA – suggesting that each of these also plays a role in ILD risk. Thus ILD was was associated with higher levels of anti-CCP titers, regardless of a diagnosis of RA. (Abstract #1377 Citation source http://buff.ly/1TlmLco)

Thus, the ACPA-ILD association extends beyond RA. There are several reports in the literature of CCP or ACPA positivity found in patients with inflammatory myopathy (Citation source http://buff.ly/1TlkwWu).  The association between ACPA and the anti-synthetase syndrome with as investigated by a French network and they compared 17 ACPA positive and 34 ACPA negative anti-synthetase syndrome patients and found ACPA positive patients had more arthritis, swollen joints, erosive disease and biologic use (Citation source http://buff.ly/1J6e8v8). ILD was present in 82% of patients in both groups, but patients with ACPA had higher forced volume capacity and higher diffuse lung carbon dioxide than the ACPA-negative group.

The association between ACPA and ILD seems to extend beyond RA and may be seen in patients with myositis (anti-synthetase syndrome), MCTD and lupus as well. While ACPA itself may be important, it is not clear that it is an independant risk factor for ILD.  Instead, the well known association between ACPA and smoking may have addititive potential in the promotion of inflammatory arthritis or interstitial lung disease.