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: Deficiency in some complement factors is known to cause both systemic lupus erythematosus (SLE) and dermatomyositis (DM). Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway, and its low levels are reported to influence some autoimmune diseases. Furthermore, MBL2 polymorphisms have been described associated with low MBL serum levels due to impaired MBL structure and function. This is a pilot study to investigate the role of MBL2-550G/C (H/L), -221G/C (Y/X), Arg52Cys (D), Gly54Asp (B), Gly57Glu (C) polymorphisms and MBL serum levels as a risk factor for a development of adult DM and SLE in Bulgarian patients. None of the studied MBL2 polymorphisms appeared associated with the diseases investigated. However, we have found an increased OR of MBL2-221XY genotype in the patients with SLE (OR 1.64, 95%CI 0.77-3.52). MBL2 polymorphisms seemed to affect MBL serum levels and to be associated with the clinical features although none of the associations remained statistically significant after Bonferroni correction. The-550L allele showed an association with electromyography findings in patients with DM. The-221XY genotype was associated with photosensitivity in patients with SLE. The 54AB genotype showed an association with malar rash in patients with SLE, but it appeared decreased among SLE patients with ANA. In conclusion, our results suggest that the MBL2 polymorphisms have rather a disease modifying role and they are not associated with the disease susceptibility in adult DM and SLE among Bulgarian patients.
    International Journal of Immunogenetics 03/2014; 41(2):119-125. DOI:10.1111/iji.12093 · 1.34 Impact Factor
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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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    ABSTRACT: Understanding the pathogenesis of systemic lupus erythematosus (SLE) remains a considerable challenge. Multiple abnormalities of both the innate and adaptive immune systems have been described to be associated with the disease. As a part of the complement mannose-binding lectin (MBL) plays an important role in the innate immunity which is well demonstrated by its ability to suppress the LPS-mediated up-regulation of specific pro-inflammatory cytokines. Recent studies aimed to investigate its role as a biomarker of systemic lupus erythematosus. Low levels of MBL impair the clearance of apoptotic material leading to the production of autoantibodies and/or appearance of circulation immune complexes which can cause renal deposits, while increased MBL enhance the activation of the complement system leading to tissue damage observed in severe disease including lupus nephritis. The genetic variants of MBL gene can influence its serum production and thus they appear to be associated with the disease, too. The present review summarizes our experience, as well as the previously reported data in literature about the involvement of MBL and MBL2 genetic variants in the pathogenesis of SLE, its clinical manifestations and outcome.
    Systemic Lupus Erythematosus (SLE): Prevalence, Pathophysiology and Prognosis, Edited by Syuichi Koarada, 09/2013: chapter MBL and MBL Genotypes in SLE: pages 81-99; Nova Publishers., ISBN: 978-1-62948-041-1

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