Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients

This study describes the importance of mannose-binding lectin (MBL) variant alleles for systemic lupus erythematosus (SLE) and accompanying infections in a population-based cohort. MBL alleles were determined in 99 SLE patients recruited from a representative Danish region. Patients were classified according to the 1982 revised ACR criteria as definite SLE (D-SLE) (n = 77) fulfilling greater than or equal to4 criteria and incomplete SLE (I-SLE) (n = 22) with <4 criteria. A total of 250 healthy volunteers served as controls. MBL variant alleles were observed in 51.9% of D-SLE patients (odds ratio: 1.8) and 36.4% (odds ratio: 1.0) of I-SLE patients compared with 37.2% of the controls (P = 0.02 and P > 0.99, respectively). A meta-analysis of eight previously published studies suggested that the presence of MBL variant alleles confer a 1.6 times overall increased risk for D-SLE (P < 0.00001). MBL variant allele carriers had higher disease activity (SLEDAI-index) in a 2-year follow-up period (P = 0.02) and had an increased risk of acquiring complicating infections in general (P = 0.03) and respiratory infections in particular (P = 0.0006). Only in SLE patients fulfilling <greater than or equal to>4 ACR criteria an increased frequency of MBL variant alleles was found. MBL variant alleles were also associated with increased risk of disease activity and of complicating infections indicating that the MBL gene is an SLE disease modifier locus.