Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis
1 Department of Rheumatology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark and Institute of Clinical Research, University of Southern Denmark, Winsloewparken 19, DK-5000 Odense C, Denmark
2 Medical Biotechnology Centre, University of Southern Denmark, Winsloewparken 25, DK-5000 Odense C, Denmark
3 Department of Rheumatology, Rheumatism Hospital, Toldbodgade 3, DK-6300 Graasten, Denmark
4 Department of Rheumatology, Copenhagen University Hospitals, Hvidovre and Glostrup, Kettegaards Alle 30, DK-2650 Hvidovre, Denmark
5 Department of Rheumatology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus C, Denmark
6 Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
7 Department of Rheumatology, Copenhagen University Hospitals, Herlev and Gentofte, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark
8 Department of Radiology, Copenhagen University Hospital, Hvidovre, Kettegaards Alle 30, DK-2650 Hvidovre, Denmark
9 Department of Radiology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus C, Denmark
Arthritis Research & Therapy 2010, 12:R39 doi:10.1186/ar2948Published: 8 March 2010
Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA.
One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed.
Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings.
This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation.