Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic lupus erythematosus

Abstract

Mannose-binding lectin (MBL) is a key element in innate immunity with functions and structure similar to that of complement C1q. It has been reported that MBL deficiency is associated with occurrence of systemic lupus erythematosus (SLE). We hypothesized that anti-MBL antibodies, if present, would affect the occurrence or disease course of SLE, by reduction of serum MBL levels, interference of MBL functions, or binding to MBL deposited on various tissues. To address this hypothesis, we measured the concentration of anti-MBL antibodies in sera of 111 Japanese SLE patients and 113 healthy volunteers by enzyme immunoassay. The titres of anti-MBL antibodies in SLE patients were significantly higher than those in healthy controls. When the mean + 2 standard deviations of controls was set as the cut off point, individuals with titres of anti-MBL antibodies above this level were significantly more frequent in SLE patients (9 patients) than in controls (2 persons). One SLE patient had an extremely high titre of this antibody. No associations of titres of anti-MBL antibodies and (i) genotypes of MBL gene, (ii) concentrations of serum MBL, or (iii) disease characteristics of SLE, were apparent. Thus, we have confirmed that anti-MBL antibodies are indeed present in sera of some patients with SLE, but the significance of these autoantibodies in the pathogenesis of SLE remains unclear.

Fig. 1

Autoantibodies to mannose-binding lectin (MBL) in serum samples. Anti-MBL antibodies were measured in 111 samples from patients with systemic lupus erythematosus (SLE) and in 113 samples from healthy controls, in the presence of EDTA (1 mm). Dotted line indicates 2 standard deviation (s.d.) above average in healthy controls. P-value by Mann–Whitney U-test. aU, arbitrary units.

Fig. 2

Titration curve and inhibition assay for autoantibodies to mannose-binding lectin (MBL). (a) Titration curve for anti-MBL antibodies using serial dilutions of the standard serum in the presence of EDTA (1 mm). (b) Inhibition assay for anti MBL antibodies adding excess amount of recombinant MBL to diluted standard serum in the presence of EDTA (1 mm).

Fig. 3

Serum mannose-binding lectin (MBL) concentrations in 111 patients with systemic lupus erythematosus (SLE) and 113 healthy controls. Subjects with homozygosity for the codon 54 wild-type allele (□), subjects with heterozygosity for the codon 54 variant (▪), and subjects with homozygosity for the codon 54 variant allele (Δ) are indicated in both patients with SLE and healthy controls. Dotted lines indicate average of titres of serum MBL concentrations in each genotype on both groups. P-value by Mann–Whitney U-test.

Fig. 4

Association between genotypes of the mannose-binding lectin (MBL) gene and levels of anti-MBL antibodies in patients with systemic lupus erythematosus (SLE). AA; homozygosity for the codon 54 wild-type allele, AB; heterozygosity for the codon 54 variant, BB; homozygosity for the codon 54 variant allele. Dotted lines indicate average of titres of anti-MBL antibodies in each genotype. aU, arbitrary units.

Fig. 5

Association between titres of anti mannose-binding lectin (MBL) antibodies and concentrations of MBL in systemic lupus erythematosus (SLE) patients. P-value by Spearman's rank correlation test. aU, arbitrary units.