Article

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: 9.27). 03/2005; 64(2):311-4. DOI: 10.1136/ard.2003.020172
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Background and Aims: Systemic lupus erythematosus (SLE) is an autoimmune disease in which the complement system plays a crucial role in its pathogenesis. Mannan-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement activation. The presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations in MBL serum concentration. MBL variant alleles that lead to low serum levels and/or functional deficits of MBL are postulated to contribute to the susceptibility of SLE. Moreover, the influence of MBL variation on antibody production and renal involvement in SLE patients remains controversial. Therefore, MBL serum level and genotypes were studied in our SLE Egyptian patients with evaluation of its role in auto antibodies production and lupus nephritis development. Methods: MBL genotypes and serum level were screened in a case control study that included 30 SLE patients as well as 30 healthy controls. MBL polymorphism at exon 1 codons 54 and 57 was detected by PCR using sequence-specific priming (SSP) and serum MBL level was determined by ELISA technique. Results: There was predominance of AA genotype (80%) in control group. Genotype frequencies of MBL variants in patients with SLE showed significant differences when compared with controls (AA 53.3% vs 80%, P=0.03, OR = 0.29 and AO+OO 46.6% vs 20%, P = 0.03, OR = 3.5, respectively). Serum MBL in our SLE patients (900 ng/ml) was significantly lower than that of the control group (2750 ng/ml, P = 0.00) with positive correlation with low MBL genotypes. SLE patients with mutant alleles were more likely to produce anti dsDNA (92.8% vs 75%, OR = 4.3) and anti-Smith (35.7% vs 18.7%, OR = 2.3). Patients carrying MBL-low genotypes have an increased risk of development of lupus nephritis than those carrying MBL-high genotype (64.7% vs 35.2%, P = 0.02, OR= 2.4). Conclusions: MBL gene polymorphism is associated with low MBL serum levels that were found with significantly increased frequency in our SLE patients and it may be one of the genetic factors that determine the susceptibility to develop lupus nephritis.

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May 15, 2014