Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis

被引:19
作者
Christensen, Anne Friesgaard [1 ,2 ]
Sorensen, Grith Lykke [3 ]
Horslev-Petersen, Kim [4 ]
Holmskov, Uffe [3 ]
Lindegaard, Hanne Merete [1 ,2 ]
Junker, Kirsten [3 ]
Hetland, Merete Lund [5 ]
Stengaard-Pedersen, Kristian [6 ]
Jacobsen, Soren [7 ]
Lottenburger, Tine [4 ]
Ellingsen, Torkell [6 ]
Andersen, Lis Smedegaard [4 ]
Hansen, Ib [6 ]
Skjodt, Henrik [5 ]
Pedersen, Jens Kristian [4 ]
Lauridsen, Ulrik Birk [5 ]
Svendsen, Anders [1 ,2 ]
Tarp, Ulrik [6 ]
Podenphant, Jan [8 ]
Vestergaard, Aage [9 ]
Jurik, Anne Grethe [10 ]
Ostergaard, Mikkel [6 ]
Junker, Peter [1 ,2 ]
机构
[1] Odense Univ Hosp, Dept Rheumatol, DK-5000 Odense C, Denmark
[2] Univ So Denmark, Inst Clin Res, DK-5000 Odense C, Denmark
[3] Univ So Denmark, Ctr Med Biotechnol, DK-5000 Odense C, Denmark
[4] Rheumatism Hosp, Dept Rheumatol, DK-6300 Grasten, Denmark
[5] Copenhagen Univ Hosp, Dept Rheumatol, DK-2650 Hvidovre, Denmark
[6] Aarhus Univ Hosp, Dept Rheumatol, DK-8000 Aarhus C, Denmark
[7] Rigshosp, Copenhagen Univ Hosp, Dept Rheumatol, DK-2100 Copenhagen, Denmark
[8] Copenhagen Univ Hosp, Dept Rheumatol, DK-2900 Hellerup, Denmark
[9] Copenhagen Univ Hosp, Dept Radiol, DK-2650 Hvidovre, Denmark
[10] Aarhus Univ Hosp, Dept Radiol, DK-8000 Aarhus C, Denmark
关键词
MANNOSE-BINDING LECTIN; APOPTOTIC CELLS; PSEUDOMONAS-AERUGINOSA; SYNOVIAL PERMEABILITY; CLINICAL REMISSION; SERUM-LEVELS; SFTPD GENE; IN-VIVO; CLEARANCE; POLYMORPHISMS;
D O I
10.1186/ar2948
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: 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. Methods: One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naive 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. Results: 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. Conclusions: 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.
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页数:9
相关论文
共 53 条
[1]  
Arend WP, 2001, ARTHRITIS RHEUM, V44, P2224, DOI 10.1002/1529-0131(200110)44:10<2224::AID-ART384>3.3.CO
[2]  
2-8
[3]   THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].
ARNETT, FC ;
EDWORTHY, SM ;
BLOCH, DA ;
MCSHANE, DJ ;
FRIES, JF ;
COOPER, NS ;
HEALEY, LA ;
KAPLAN, SR ;
LIANG, MH ;
LUTHRA, HS ;
MEDSGER, TA ;
MITCHELL, DM ;
NEUSTADT, DH ;
PINALS, RS ;
SCHALLER, JG ;
SHARP, JT ;
WILDER, RL ;
HUNDER, GG .
ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324
[4]   A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis [J].
Bathon, JM ;
Martin, RW ;
Fleischmann, RM ;
Tesser, JR ;
Schiff, MH ;
Keystone, EC ;
Genovese, MC ;
Wasko, MC ;
Moreland, LW ;
Weaver, AL ;
Markenson, J ;
Finck, BK .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (22) :1586-1593
[5]   An Explanation for the Apparent Dissociation Between Clinical Remission and Continued Structural Deterioration in Rheumatoid Arthritis [J].
Brown, A. K. ;
Conaghan, P. G. ;
Karim, Z. ;
Quinn, M. A. ;
Ikeda, K. ;
Peterfy, C. G. ;
Hensor, E. ;
Wakefield, R. J. ;
O'Connor, P. J. ;
Emery, P. .
ARTHRITIS AND RHEUMATISM, 2008, 58 (10) :2958-2967
[6]   Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission - Evidence from an imaging study may explain structural progression [J].
Brown, A. K. ;
Quinn, M. A. ;
Karim, Z. ;
Conaghan, P. G. ;
Peterfy, C. G. ;
Hensor, E. ;
Wakefield, R. J. ;
O'Connor, P. J. ;
Emery, P. .
ARTHRITIS AND RHEUMATISM, 2006, 54 (12) :3761-3773
[7]   Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide [J].
Bufler, P ;
Schmidt, B ;
Schikor, D ;
Bauernfeind, A ;
Crouch, EC ;
Griese, M .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2003, 28 (02) :249-256
[8]   SURFACTANT PROTEIN-D - SUBCELLULAR-LOCALIZATION IN NONCILIATED BRONCHIOLAR EPITHELIAL-CELLS [J].
CROUCH, E ;
PARGHI, D ;
KUAN, SF ;
PERSSON, A .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (01) :L60-L66
[9]  
CROUCH E, 1994, J BIOL CHEM, V269, P15808
[10]   By binding SIRPα or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation [J].
Gardai, SJ ;
Xiao, YQ ;
Dickinson, M ;
Nick, JA ;
Voelker, DR ;
Greene, KE ;
Henson, PM .
CELL, 2003, 115 (01) :13-23