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THU0050 Circulating Lung Surfactant Protein D (SP-D) Differs Between Rheumatoid Arthritis (RA) Patients According to Anti-Citrullinated Protein Antibody (Anti-CCP) and IGM-Rheumafactor (IGM-RF) Status
  1. H. M. Lindegaard1,1,
  2. K. Horslev-Petersen2,
  3. T. Lorenzen3,
  4. J. Raun2,
  5. L. B. Jensen2,
  6. G. Soerensen4,
  7. A. F. Christensen1,
  8. P. Junker1
  1. 1Rheumatology, University Hospital in Odense, Odense
  2. 2Department of Rheumatology, Rheumatism Hospital in Graasten, University of Southern Denmark, Graasten
  3. 3Department of Internal Medicine, section of Rheumatology, Vejle Hospital, Vejle
  4. 4Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

Abstract

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

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