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.

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
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 36 Issue 4 Pg. 731-5 (Apr 2009) ISSN: 0315-162X [Print] Canada
• PMID: 19273450 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• MBL2 protein, human
• Mannose-Binding Lectin
• Peptides, Cyclic
• cyclic citrullinated peptide

Topics

• 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)
• Severity of Illness Index
• Surveys and Questionnaires
• Young Adult