Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

Abstract

Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

Practical Approach to the Evaluation and Management of Rheumatoid Arthritis-Interstitial Lung Disease based on its Proven and Hypothetical Mechanisms

“…The ACPA titers have shown to correlate to the number of lymphoid follicles in the lung biopsy of RA ILD patients in one study 27 . This clearly suggests that the lung contributes to the total pool of circulating 29 . As a consequence, the presence of high ACPA titers (defined as an elevation of the titers more than three times the upper limit of normality) in an RA patient with ILD may be evidence of an immune response taking place at the lung 30 .…”

Lung inflammation in the pathogenesis of rheumatoid arthritis

“…It can be argued that RA alone is a risk factor for lung disease; however, there are also several factors within individuals with RA that have been associated with an increased risk of RA‐related lung disease. These factors include exposure to tobacco smoke and other inhaled factors such as occupational dust . Additional risk factors for lung disease in RA include male gender, duration of RA, high articular disease activity, seropositivity for RF and ACPA, and infections .…”

“…10,[34][35][36][37][38][39][40] Additional risk factors for lung disease in RA include male gender, duration of RA, high articular disease activity, seropositivity for RF and ACPA, and infections. 10,[34][35][36][37][38][39][40] Medications may play a role in lung disease in RA, and in particular, methotrexate has long been considered a risk factor for ILD; however, a recent large-scale analyses have demonstrated that methotrexate is not significantly associated with ILD and may indeed be protective. 41,42 Importantly, however, there are different forms of lung disease in RA (eg, AD, ILD), and the type of lung disease has differing underlying biology as well as risk factors.…”

Rituximab therapy in interstitial lung disease associated with rheumatoid arthritis

“…Although an increased prevalence of ILD has been reported in smokers than in non‐smokers, the role of the smoking history in ILD development is still unclear. It has been suggested that smoking and other environmental factors can induce the production of citrullinated proteins and anti‐citrullinated antibodies that promote the lung inflammatory processes …”

“…It has been suggested that smoking and other environmental factors can induce the production of citrullinated proteins and anti-citrullinated antibodies that promote the lung inflammatory processes. 8,9 The principal symptoms associated with RA-ILD are exertional dyspnoea and dry cough, however, a variable percentage of patients ranging from 30 to 90% are asymptomatic or show mild symptoms. 7 A restrictive pattern at pulmonary function tests (PFT) with reduced diffusing capacity of the lung for carbon monoxide (DLCO) percentages are the most frequent functional alterations.…”