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.
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.
Jacobsen
Søren
S
Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. sj@dadlnet.dk
Garred
Peter
P
Madsen
Hans Ole
HO
Heegaard
Niels H H
NH
Hetland
Merete Lund
ML
Stengaard-Pedersen
Kristian
K
Junker
Peter
P
Lottenburger
Tine
T
Ellingsen
Torkel
T
Smedegaard Andersen
Lis
L
Hansen
Ib
I
Skjødt
Henrik
H
Pedersen
Jens Kristian
JK
Lauridsen
Ulrik Birk
UB
Svendsen
Anders J
AJ
Tarp
Ulrik
U
Pødenphant
Jan
J
Lindegaard
Hanne
H
Vestergaard
Aage
A
Østergaard
Mikkel
M
Hørslev-Petersen
Kim
K
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
D001323:Autoantibodies; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide