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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.