Background Subclinical lung inflammation has been proposed as a triggering mechanism for the generation of anti-CCP. This concept has recently been supported by imaging studies showing clinically silent parenchymal lung changes in autoantibody positive subjects without arthritis. SP-D belongs to the collectin family of the innate immune system and is primarily expressed in pulmonary Clara cells. Lung irritants like smoking increase SP-D expression locally and in the systemic circulation.
Objectives Based on this we hypothesized, that SP-D in serum would differ between anti-CCP seropositive vs. seronegative RA-patients.
Methods 741 Danish patients with established RA according to the 1987 ACR revised criteria were enrolled in a cross-sectional study. Patients with lung disease were excluded. 1476 twin individuals served as controls. SP-D was quantified in serum by ELISA.
Results Median symptom duration upon inclusion was 9 years (IQ 3,6-17), median age 62 years (IQ 54-70), female:male ratio was 3:1. 508 (69 %) were IgM RF factor positive, and 397 (54 %) were anti-CCP positive. 211 (28%) were current smokers, 311 (42%) previous smokers and 218 (30 %) were non-smokers. Extraarticular disease was diagnosed in 233 (31%). SP-D was significantly higher in RA-patients compared to healthy controls (1119 ng/ml [724-1831] vs. 913 ng/ml [604-1387], p < 0,001), but not after adjustment for smoking, age and gender. Similarly, SP-D did not differ between patients with respect to IgM-RF status. By contrast, SP-D was significantly higher in anti-CCP positive vs. anti-CCP negative RA-patients (1211 ng/ml [780;-1937] vs. 990 ng/ml [689 -1531], p = 0,0005), even after adjustment for smoking, age and gender (p < 0,001). In anti-CCP negative smokers SP-D was higher than in non-smokers (1184 ng/ml [818-2044] vs. 934 ng/ml [652 -1371] (p = 0,004), also when adjusted for age and sex (p = 0,007).
Conclusions Lung surfactant protein-D was increased in RA smokers compared with RA non-smokers and healthy controls. In addition, SP-D was significantly higher in non-smoking, anti-CCP positive vs. non-smoking anti-CCP negative RA-patients. A similar pattern could not be detected concerning IgM rheumatoid factor. Although there is a high concordance between seropositivity for IgM-RF and anti-CCP, this observation suggests that the expression of these two RA-related autoantibodies are regulated via common as well as separate pathways. Our findings add to the concept of a pathogenetic link between lung- and joint inflammation in anti-CCP positive RA.
Disclosure of Interest H. Lindegaard Grant/research support from: MSD, BMS, Roche, K. Horslev-Petersen: None Declared, T. Lorenzen Grant/research support from: Roche, Pzeifer, BMS, Abbott, J. Raun: None Declared, L. Jensen: None Declared, G. Soerensen: None Declared, A. Christensen: None Declared, P. Junker: None Declared