Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus

Abstract

Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented in the 103 SLE patients (mean age 41 +/- 13 years, mean disease duration 7 +/- 4 years). The percentage of SLE patients with severe MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients frequently suffer from infections, but deficiency of functional MBL does not confer additional risk.

Figure 1

Dependence of C4 deposition assay on C4 serum concentration. C4 deposition was measured in a dilution curve of serum of two healthy donors in the presence of a constant mannose-binding lectin concentration of 200 ng/ml. C4 deposition becomes C4-dependent at a concentration below 0.001 g/l. Because sera with low C4 deposition (<10%) are evaluated at a dilution of 1:10, the minimal required C4 concentration in a tested serum will be 0.01 g/l.

Figure 2

Mannose-binding lectin (MBL) serum level, C4 deposition, and MBL pathway activity. Functional MBL activity measured by three assays in all patients with systemic lupus erythematosus (SLE; n = 103), a subgroup of SLE patients without infections (SLEno; n = 52), a subgroup of patients with SLE who had minor infections only (SLEmin; n = 28), a subgroup of SLE patients with one or more major infections (SLEmaj; n = 23), and healthy controls. (a) MBL serum levels. (b) Complement C4 deposition. (c) MBL pathway activity. Each datapoint represents one patient. Bars show the median values. No significant differences were found between the median functional MBL activity of all patients with SLE and each of the subgroups or between the subgroups, as measured with three assays (data not shown).