Document Detail


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.
MedLine Citation:
PMID:  19273450     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. CONCLUSION: 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:
Søren Jacobsen; Peter Garred; Hans Ole Madsen; Niels H H Heegaard; Merete Lund Hetland; Kristian Stengaard-Pedersen; Peter Junker; Tine Lottenburger; Torkel Ellingsen; Lis Smedegaard Andersen; Ib Hansen; Henrik Skjødt; Jens Kristian Pedersen; Ulrik Birk Lauridsen; Anders J Svendsen; Ulrik Tarp; Jan Pødenphant; Hanne Lindegaard; Aage Vestergaard; Mikkel Østergaard; Kim Hørslev-Petersen
Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-02-27
Journal Detail:
Title:  The Journal of rheumatology     Volume:  36     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-03     Completed Date:  2009-06-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  731-5     Citation Subset:  IM    
Affiliation:
Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. sj@dadlnet.dk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Arthritis, Rheumatoid / genetics*,  immunology,  pathology,  physiopathology*
Autoantibodies / blood,  immunology*
Disability Evaluation
Double-Blind Method
Female
Humans
Mannose-Binding Lectin / genetics*
Middle Aged
Peptides, Cyclic / immunology*
Polymorphism, Genetic*
Promoter Regions, Genetic / genetics
Questionnaires
Severity of Illness Index
Young Adult
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/MBL2 protein, human; 0/Mannose-Binding Lectin; 0/Peptides, Cyclic; 0/cyclic citrullinated peptide

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