Two edged role of mannose binding lectin in rheumatoid arthritis: a cross sectional study.
OBJECTIVE
We investigated whether polymorphisms in the gene of mannose binding lectin (MBL) may be associated with onset of rheumatoid arthritis (RA), and whether MBL in conjunction with aggregated agalactosyl IgG (IgG-G0) may be associated with clinical and paraclinical variables.


METHODS
MBL genotypes and serum concentrations were measured by polymerase chain reaction and ELISA in 189 patients with established RA. Binding of purified MBL to IgG-G0 in serum was assessed and clinical and paraclinical variables were recorded.


RESULTS
The median age at onset of RA in the 3 genotypes (normal: A/A, hetero: A/0, and homozygous: 0/0 for variant alleles) was 54.1 (n = 108), 47.0 (n = 68), and 38.4 years (n = 13), respectively (p = 0.01). The frequency of variant alleles in patients with onset below the median age (50.8 yrs) was 0.32, but was 0.17 in patients with onset above 50.8 years (p = 0.003) and 0.20 in 250 controls (p = 0.001). Stratification according to erosion score (no, small, large) revealed an increasing tendency among the different groups in binding of MBL to IgG-G0, increased Health Assessment Questionnaire score, and acute phase reactants in A/A individuals, while no difference was seen among carriers of variant alleles. This effect was most pronounced in those with late onset RA.


CONCLUSIONS
Presence of MBL variant alleles was associated with early onset of RA. MBL deficiency may, therefore, accelerate the disease. However, in patients with late onset and advanced disease our results indicate that the A/A type may be associated with additional inflammation different from that seen in carriers of variant alleles.
Garred
P
P
Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital (Rigshospitalet), Copenhagen, Denmark. Garred@post5.tele.dk
Madsen
H O
HO
Marquart
H
H
Hansen
T M
TM
Sørensen
S F
SF
Petersen
J
J
Volck
B
B
Svejgaard
A
A
Graudal
N A
NA
Rudd
P M
PM
Dwek
R A
RA
Sim
R B
RB
Andersen
V
V
D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D037222:Collectins; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged
D002352:Carrier Proteins; D037222:Collectins; D007074:Immunoglobulin G; C064155:agalactosyl IGG; D008358:Mannose