The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis

Objective. To determine whether variant alleles of the mannose binding lect in (MBL) gene causing low serum concentrations of MBL are associated with i ncreased susceptibility to rheumatoid arthritis (RA) and erosive outcome in an inception cohort of patients with early polyarthritis. Methods. MBL and HLA-DRB1 alleles were determined by polymerase chain react ion in 68 Danish patients with incident early polyarthritis observed for on e year. The associations between MBL and specific HLA-DRB1 genotypes and di sease outcomes were analyzed. Results, Among the patients with early polyarthritis 7.4% (5/68) and 41.2% (28/68) were homozygous and heterozygous for MBL variant alleles, compared with 2.8% (7/250) and 33.4% (86/250) of healthy controls (p = 0.09), while the corresponding figures in the patients with RA were 10% (5/50) and 42% ( 21/50) (p = 0.03), and in the patients with erosive RA 18.8% (3/16) acid 35 .3% (6/16, respectively (p = 0.004). Patients with early polyarthritis homo zygous for MBL variant alleles had an increased risk of having erosive RA a t inclusion by a factor of 4.7 (p = 0.02) and after one year by a factor of 3.6; (p = 0.04). MBL deficiency was associated with increased levels of C reactive protein (CRP) and IgM rheumatoid factor (RF) at inclusion (P < 0.0 5). HLA-DRB1 alleles were not found to be associated with disease outcome. Conclusion, MBL variant alleles appear to be weak susceptibility markers fo r RA and patients with early polyarthritis and homozygous for MBL structura l variant alleles have a higher risk of developing early erosive RA. These findings, together with the positive association between MBL variant allele s and the increased serum levels of IgM RF and CRP, point at the MBL gene a s a relevant locus in the pathophysiology of RA.