Background/Purpose: The identification of peripheral blood markers of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) may facilitate an earlier diagnosis and provide insight regarding the pathogenesis of this severe disease complication. Antibodies directed against citrullinated fibrinogen (AhFibA) and the α36-50Cit and β60-74Cit peptides exhibiting its immunodominant epitopes are associated with radiographic damages in RA but have not been yet studied in RA-ILD. The aim of this study was to characterize the profile of anti-α36-50Cit and anti-β60-74Cit subfamilies of AhFibA in RA-ILD.

Methods: Anti-CCP2, AhFibA and their anti-α36-50Cit and anti-β60-74Cit subfamilies were assayed by ELISA in a population of RA-ILD (n=75), RA-noILD (n=75) patients and in a control group of idiopathic pulmonary fibrosis (IPF) patients (n=75). RA was diagnosed according to ACR 1987 and/or ACR/EULAR 2010 criteria. ILD status was assessed with High-resolution computed tomography (HRCT) in all the patients.

Results: Using a 98.5% specificity level, anti-CCP2, AhFibA and their anti-α36-50Cit and anti-β60-74Cit subfamilies were detected in 66%, 65%, 36% and 62% of RA patients, respectively whereas they were not detected in the majority of IPF patients (1%) (Table 1). No significant difference was observed for the sensibility of the different antibodies for the identification of ILD among RA patients. Anti-CCP2, AhFibA and anti-β60-74Cit titers were significantly lower in RA-ILD patients compared to RA-noILD patients (Table 1) whereas there was a trend for higher anti-α36-50Cit autoantibodies (P=0.145; ns). Within AhFibA positive RA patients, anti-α36-50Cit were more frequently observed in those having ILD (66% vs 33, P=0.013). In addition, anti-α36-50Cit antibody titers correlated with those of AhFibA only in RA-ILD patients (Figure 1).

Conclusion: Specific qualitative and quantitative profiles of anti-α36-50Cit and anti-β60-74Cit autoantibodies subfamilies of AhFibA are associated with the occurrence of ILD in the context of RA.

Table 1. Distribution of different autoantibodies in the 3 groups (RA-ILD, RA-noILD, IFP). Positivity rate is expressed in number of patients (%), Titers are expressed as median (min-max).

Figure 1. Correlation between AhFibA titers with anti-β60-74Cit or anti-α36-50Citautoantibody titers in RA-noILD population (A and B) and in RA-ILD population (C and D).