title: Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis.
abstract: OBJECTIVE
  To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA).
  
  
  METHODS
  Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score).
  
  
  RESULTS
  Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs.
  
  
  CONCLUSIONS
  The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.
authors.affiliation: Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. sj@dadlnet.dk
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Hans Ole
authors.initials: HO
authors.lastname: Madsen
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.forename: Tine
authors.initials: T
authors.lastname: Lottenburger
authors.forename: Torkel
authors.initials: T
authors.lastname: Ellingsen
authors.forename: Lis
authors.initials: L
authors.lastname: Smedegaard Andersen
authors.forename: Ib
authors.initials: I
authors.lastname: Hansen
authors.forename: Henrik
authors.initials: H
authors.lastname: Skjødt
authors.forename: Jens Kristian
authors.initials: JK
authors.lastname: Pedersen
authors.forename: Ulrik Birk
authors.initials: UB
authors.lastname: Lauridsen
authors.forename: Anders J
authors.initials: AJ
authors.lastname: Svendsen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Tarp
authors.forename: Jan
authors.initials: J
authors.lastname: Pødenphant
authors.forename: Hanne
authors.initials: H
authors.lastname: Lindegaard
authors.forename: Aage
authors.initials: A
authors.lastname: Vestergaard
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide