Mannose-binding lectin is a disease-modifying factor in North American patients with systemic lupus erythematosus

To investigate whether development of systemic lupus erythematosus (SLE), its clinical manifestations, and autoantibody production are associated with polymorphisms of the mannose-binding lectin (MBL) gene in North American patients with SLE.

MBL gene polymorphisms in codons 52 (designated variant D, with the wild-type designated A), 54 (variant B), and 57 (variant C) were determined by polymerase chain reaction-sequence specific priming in 130 patients with SLE and 142 healthy controls. Autoantibodies against double-stranded DNA (dsDNA), Smith antigen, phospholipids, Ro/SSA, La/SSB, and RNP were tested at certified clinical pathology laboratories.

A statistically significant increased likelihood of anti-Smith antibody production was observed in SLE patients with the heterozygous A/B genotype [odds ratio (OR) 5.1; 95% confidence interval (CI) 1.6-16.6; the A/A genotype as the reference group] or A/C genotype (OR 8.2; 95% CI 2.0-33.9). SLE patients with the homozygous or compound heterozygous variant genotype (O/O; O, a common designation for variant alleles) had an increased likelihood of mounting autoantibody responses against dsDNA, Ro/SSA, and La/SSB, and were more likely to have a history of renal disease (OR 4.8; 95% CI 0.9-25.2). However, differences in the frequencies of MBL variant alleles and genotypes observed between patients with SLE and controls did not reach statistical significance.

A significantly increased prevalence of anti-Smith antibody was associated with the heterozygous genotypes A/B and A/C. Although MBL structural gene polymorphism was not a risk factor for SLE development in this study population, homozygosity of MBL variant alleles may be a weak disease-modifying factor, particularly for renal involvement, in North American patients with SLE.