Association of mannose binding lectin (MBL) gene polymorphism and serum MBL concentration with characteristics and progression of systemic lupus erythematosus

Division of Rheumatology, Department of General Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-city, Ibaraki 305-8575, Japan.
Annals of the Rheumatic Diseases (Impact Factor: 10.38). 03/2005; 64(2):311-4. DOI: 10.1136/ard.2003.020172
Source: PubMed


To determine whether occurrence, characteristics, and progression of systemic lupus erythematosus (SLE) are associated with polymorphism of the mannose binding lectin (MBL) gene and with serum MBL concentration.
Codon 54 MBL gene polymorphism of 147 patients with SLE and 160 healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism. Serum concentration of MBL was measured by enzyme immunoassay. Fluctuations of serum MBL were analysed with respect to disease characteristics and activity.
Frequency of homozygosity for codon 54 minority allele was 6% (9/147) in patients with SLE, and significantly higher than in controls (p = 0.0294, Fisher's exact test). MBL polymorphism in patients with SLE was not significantly associated with disease characteristics or immunological phenotypes. Patients homozygous for the B allele tended to have a higher risk of infection during treatment. Levels of C3 and CH(50) were slightly, but significantly, associated with serum MBL concentration in patients with SLE homozygous for the majority allele. During the course of SLE, serum MBL concentration increased in 6/14 patients, and decreased in 7 after initiation of immunosuppressive treatment.
MBL gene polymorphism influences susceptibility to SLE, but has no direct effect on disease characteristics. Serum MBL levels fluctuate during the course of SLE in individual patients. MBL genotyping may be useful in assessing the risk of infection during treatment of SLE.

Download full-text


Available from: Akito Tsutsumi, Dec 26, 2013
25 Reads
  • Source
    • "Our study of 93 patients with lupus and 67 controls showed elevated plasma MBL in SLE compared to healthy controls corroborating the observations made in previous studies [14-16]. Interestingly, SLE patients also displayed higher plasma MBL levels compared to healthy controls with similar MBL2 genetic background [25]. Earlier reports have shown association of low-producer MBL genotypes with susceptibility to SLE [20,32,34-36]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction A role for mannose binding lectin (MBL) in autoimmune diseases has been demonstrated earlier and elevated level of MBL has been shown in systemic lupus erythematosus (SLE) patients. In the current study, we investigated MBL as a potential biomarker for disease activity in SLE. Methods In a case control study SLE patients (93 females) and 67 age, sex, ethnicity matched healthy controls were enrolled. Plasma MBL levels were quantified by enzyme linked immunosorbent assay (ELISA). Clinical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedures. Results Plasma MBL levels were significantly high in SLE patients compared to healthy controls (P < 0.0001). MBL levels were variable in different clinical categories of SLE. Lower levels were associated with musculoskeletal and cutaneous manifestations (P = 0.002), while higher and intermediate MBL levels were significantly associated with nephritis in combination with other systemic manifestations (P = 0.01 and P = 0.04 respectively). Plasma MBL correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P = 0.0003, r = 0.36), anti-dsDNA (P < 0.0001, r = 0.54), proteinuria (P < 0.0001, r = 0.42) and negatively correlated with C3 (P = 0.007, r = -0.27) and C4 (P = 0.01, r = -0.29). Conclusions Plasma MBL is a promising marker in the assessment of SLE disease activity.
    Arthritis research & therapy 10/2012; 14(5):R218. DOI:10.1186/ar4057 · 3.75 Impact Factor
  • Source
    • "Several assays are available for the quantification of MBL, either functionally (mannan assay) or non-functionally (sandwich ELISA)(Petersen et al., 2001;Thiel et al., 2002;Roos et al., 2003;Takahashi et al., 2005;Seelen et al., 2005a). However, these assays cannot fully investigate the functional status of the early lectin pathway cascade proteins in a single analysis to the level of C3 cleavage. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The humoral response to invading pathogens is mediated by a repertoire of innate immune molecules and receptors able to recognize pathogen-associated molecular patterns. Mannose binding lectin (MBL) and ficolins are initiation molecules of the lectin complement pathway (LCP) that bridge innate and adaptive immunity. Activation of the MBL-dependent lectin pathway, to the level of C3 cleavage, requires functional MASP-2, C2, C4 and C3, all of which have been identified with genetic polymorphisms that can affect protein concentration and function. Current assays for MBL and MASP-2 lack the ability to assess activation of all components to the level of C3 cleavage in a single assay platform. We developed a novel, low volume, fluorochrome linked immunoassay (FLISA) that quantitatively assesses the functional status of MBL, MASP-2 and C3 convertase in a single well. The assay can be used with plasma or serum. Multiple freeze/thaw cycles of serum do not significantly alter the assay, making it ideal for high throughput of large sample databases with minimal volume use. The FLISA can be used potentially to identify specific human disease correlations between these components and clinical outcomes in already established databases.
    Journal of Immunological Methods 07/2007; 323(2):147-59. DOI:10.1016/j.jim.2007.04.004 · 1.82 Impact Factor
  • Source
    • "More recently, the lectin pathway of complement activation has also been suggested to play a role in the pathogenesis of SLE [7] and in the occurrence of infections in SLE [8-10]. Mannose-binding lectin (MBL) is a serum protein with characteristics very similar to those of C1q [11]. "
    [Show abstract] [Hide abstract]
    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.
    Arthritis research & therapy 02/2006; 8(6):R183. DOI:10.1186/ar2095 · 3.75 Impact Factor
Show more