[The role of mannose binding lectin in the pathogenesis of systemic lupus erythematosus].
ABSTRACT To detect the serum level of mannose binding lectin (MBL) and its genovariation in systemic lupus erythematosus (SLE) patients and to investigate the role of MBL in the pathogenesis of SLE.
ELISA was used to measure the serum MBL level of 40 SLE patients and 30 healthy blood donors. Tm genotyping method was used for the first timer in China. Primers and specific fluorophore-labelled hybridization probes for the exon 1 and promoter regions of MBL gene were designed based on the haplotype MBL2(*) LXPA (GenBank X15422). The genotyping of MBL in these two groups were performed using real-time PCR through Light Cycler Instrument.
(1) The serum MBL of the SLE patients was 107.2 microg/L, significantly lower than that of the healthy blood donors (290.2 microg/L, P = 0.0002). (2) MBL mutation in exon 1 region was mainly at codon 54, with a mutation rate of 37.1% in the SLE group, significantly higher than that of the control group (13.3%, p = 0.049). (3) Polymorphisms of H/L in MBL gene were present in both SLE patients and controls, and there was no difference in the L allele frequency between the two groups. (4) The serum MBL level of the SLE patients with MBL mutation in codon 54 was 49.8 microg/L, significantly lower than that of the SLE patients without MBL mutation in codon 54 (141.7 microg/L, P = 0.000 27). The SLE disease activity index (SLEDAI) of the SLE patients with MBL mutation in codon 54 was 7.44, significantly lower than that of the SLE patients without MBL mutation in codon 54 (12.87, P = 0.0029). A negative correlation was observed between SLEDAI score and serum MBL (r = -0.48).
Mutation occurring in MBL exon 1 region at codon 54 may be a predisposing factor of the pathogenesis of SLE. Serum MBL may be a potential biomarker of disease activity in SLE patients.
- SourceAvailable from: Rosalind Ramsey-Goldman[show abstract] [hide abstract]
ABSTRACT: Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals. Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1. We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10⁻⁶, P = 1.9 × 10⁻⁵, P = 5.7 × 10⁻⁵, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10⁻¹¹, P = 5.2 × 10⁻⁸, P = 8.7 × 10⁻⁷ , P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region). These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities.Arthritis & Rheumatism 07/2011; 63(11):3493-501. · 7.48 Impact Factor
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ABSTRACT: The aim of this study was to determine whether the functional mannose-binding lectin (MBL2) exon 1 codon 54 polymorphism (rs1800450) confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted on the MBL2 codon 54 polymorphism across 21 comparative studies. Meta-analysis showed an association between the MBL2 codon 54 B allele and SLE in all study subjects [odds ratio (OR) = 1.298, 95% confidence interval (CI) = 1.154-1.459, P = 1.4 × 10(-5)]. Analysis after stratification by ethnicity indicated that the MBL2 codon 54 B allele is significantly associated with SLE in Europeans, Asian, and Africans (OR = 1.246, 95% CI = 1.062-1.462, P = 0.007; OR = 1.268, 95% CI = 1.049-1.532, P = 0.014; OR = 1.939, 95% CI = 1.269-2.962, P = 0.002, respectively). However, African Americans had a much lower prevalence of the T allele (5.8%) than any other populations studied, whereas Asians had the highest prevalence (16.2%). This meta-analysis confirms that the MBL2 codon 54 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.Molecular Biology Reports 12/2011; 39(5):5569-74. · 2.51 Impact Factor
Chapter: MBL and MBL Genotypes in SLE[show abstract] [hide abstract]
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.09/2013: pages 81-99; , ISBN: 978-1-62948-041-1