Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mannose binding lectin (MBL) deficiency may be associated with increased susceptibility to infection and autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, we performed for the first systematic search for mutations in all the four exons of the MBL gene using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. Of 49 healthy Japanese individuals studied, only the previously reported mutation at the codon 54 (substitution from Gly to Asp; G54D) was identified. The allele frequencies of G54D in 105 healthy Japanese individuals, 95 SLE patients and 59 RA patients, were 0.233, 0.226 and 0.178, respectively, which were not significantly different. In addition, two polymorphisms at positions of -550 and -221 in the promoter region were not associated with SLE and RA. It is unlikely that MBL deficiency plays a major role in the pathogenesis of SLE and RA in Japanese.
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PMID:Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese. 1119 79

One theory for the pathophysiology of photosensitive autoimmune skin diseases is that photoinduction of tumor necrosis factor alpha (TNFalpha) secretion leads to keratinocyte apoptosis and translocation of previously sequestered cellular antigens that then activate the immune system. We previously found an association of the overproducing TNFalpha-308 A variant with adult dermatomyositis and with subacute cutaneous lupus erythematosus. Here we focused on mannose binding lectin (MBL), which is one of several proteins involved in clearance of apoptotic cells and could thereby lessen photosensitive autoimmunity. We examined three variant MBL polymorphisms associated with decreased MBL protein (Asp54, Glu57, and the LX promoter polymorphism) in adult dermatomyositis, subacute cutaneous lupus erythematosus, and discoid lupus, and controls. The variant Asp54 allele was positively associated with adult dermatomyositis in a dose-responsive fashion (p=0.0004), as was the Glu57 allele (p=0.004). None of the three variant MBL alleles considered individually was significantly associated with either subacute cutaneous lupus erythematosus or discoid lupus. In adult dermatomyositis patients homozygous for the wild-type TNFalpha-308G allele (GG), i.e., presumably without elevated TNFalpha production, 69% had at least two of the MBL polymorphisms, versus 20% of healthy GG controls (p=0.0011). Combinations of low-producing MBL variants were over-represented in adult dermatomyositis in a dose-responsive fashion (p=0.0002). In adult dermatomyositis patients with one variant TNFalpha-308 A allele (GA), 46% had at least two MBL polymorphisms, versus 7% of GA controls (p=0.0077). Thus, low-producing MBL genes are very strongly associated with adult dermatomyositis. Our model is that genetic polymorphisms leading to overproduction of apoptotic keratinocytes and then impaired clearance of these cells contribute to the pathogenesis of adult dermatomyositis, a photoinduced autoimmune skin disease.
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PMID:Mannose binding lectin (MBL) polymorphisms associated with low MBL production in patients with dermatomyositis. 1248 45

Deficiency of mannose binding lectin (MBL), a C-type lectin with structural similarities to C1q, has been shown to predispose to the development of systemic lupus erythematosus (SLE). Some patients have low serum MBL levels which cannot be explained by either structural gene mutations or promoter polymorphisms. The objective of this study was to detect the presence of autoantibodies against MBL and to evaluate their relationship to serum MBL levels. Anti-MBL antibodies of IgM and IgG classes from consecutive SLE patients (n = 135) and healthy subjects (n = 50) were measured by an in-house ELISA. Using the 90th percentile of controls as a cutoff, more SLE patients [23.7% (32/135)] were found to have IgG anti-MBL antibodies than normal controls [10.0% (5/50)] (P = 0.04). The same trend was observed when ethnicity was taken into account by analysing Caucasians alone (n = 90). IgM anti-MBL antibodies were only found in two SLE patients (2/22, 9.1%) who had no concomitant IgG anti-MBL antibodies. Serum levels of IgG anti-MBL antibodies were found to correlate with serum MBL levels (r = 0.55, P = 0.049). However, the levels of anti-MBL antibodies did not correlate with overall disease activity. Thus the production of anti-MBL antibodies is likely to be a specific antigen-driven process. Its role in lupus pathogenesis remains to be elucidated.
Lupus 2004
PMID:Antibodies to mannose binding lectin in patients with systemic lupus erythematosus. 1535 24

Mannose binding lectin (MBL) is a serum protein with structure and functions similar to those of complement factor C1q, and is a key molecule in innate immunity. Interestingly, absence or extremely low concentration of serum MBL (MBL deficiency) seems to be a risk factor for occurrence of autoimmune diseases, in particular systemic lupus erythematosus. In addition, individuals with MBL deficiency are at risk of infection when in immunocompromised conditions. The concentration of serum MBL is greatly influenced by relatively common single nucleotide polymorphisms of the MBL gene. Therefore, typing of the MBL gene, or measurement of serum MBL may be valuable for determining the risk of infections in patients with systemic autoimmune diseases, who frequently undergo immunosuppressive therapies. MBL deficiency may also be a risk factor for atherosclerosis and arterial thrombosis, both being common complications of autoimmune diseases. On the other hand, MBL may be pathological in tissue injuries, and the precise roles of MBL in autoimmune diseases, and the value of MBL gene typing or serum MBL measurement in a clinical setting are yet to be clarified. Recently, presence of anti-MBL autoantibodies in sera of SLE patients has been reported. The significance of this autoantibody remains to be elucidated.
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PMID:Mannose binding lectin: genetics and autoimmune disease. 1608 Oct 27

C1q and mannose binding lectin, members of the "defense collagen" family, are pattern recognition molecules that can trigger rapid enhanced phagocytosis resulting in efficient containment of pathogens or clearance of cellular debris, apoptotic cells and immune complexes. In addition, interaction of C1q and mannose binding lectin with the phagocyte alters subsequent phagocyte cytokine synthesis, and thus may have important implications in directing acute inflammation as well as long-term protective immunity. The importance of the role of defense collagens in phagocytosis of apoptotic cells is highlighted by studies in vivo of mice deficient in C1q, pulmonary surfactant D and mannose binding lectin in which there is delayed clearance of apoptotic cells. Indeed, deficiency of C1q is a risk factor for the development of autoimmunity in both humans and mice, consistent with the hypothesis that inefficient clearance of apoptotic cells results in release of autoantigens and contributes to the pathology associated with autoimmune diseases such as systemic lupus erythematosus. Further understanding of the importance of C1q and mannose binding lectin in the clearance of apoptotic cells and regulation of cytokine synthesis and identification of the receptors implicated in mediating these processes should provide novel targets for therapeutic intervention in the control and manipulation of the immune response in terms of both host defense against infectious disease and tissue repair and remodeling.
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PMID:Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions. 1690 67

A functional polymorphism in PTPN22, a gene encoding a phosphatase involved in T-cell signaling, has been associated with autoimmunity. We checked for the prevalence of the PTPN22 R620W polymorphism in multiplex families affected with systemic lupus erythematosus (SLE) and other autoimmune diseases. Its association with other polymorphisms in mannose binding lectin (MBL) and FcgammaRIIa (CD32A) genes was also studied. Deoxyribonucleic acid samples were obtained from 233 Spanish individuals who belonged to 21 families in which at least two members had been diagnosed with some autoimmune disease, mainly SLE. A healthy control population was also included (n= 129). Genotyping for the R620W single-nucleotide polymorphism (SNP) was performed by restriction fragment length polymorphism analysis of polymerase chain reaction products. Allele frequency for the T allele was slightly higher in the families with autoimmune disease, especially when considering the affected individuals (0.094 vs 0.062). Actually, 18.8% affected family members vs 11.6% controls had the polymorphism (P= 0.179). Nineteen percent of affected individuals had both the PTPN22 T and the CD32A R131 alleles, whereas only 8.5% unaffected relatives had both susceptibility alleles simultaneously [P= 0.031, odds ratios 2.508 (95% confidence interval 1.066-5.896)]. The tendency toward finding the T allele more frequently in members affected with some particular autoimmune disorder suggests that this SNP may confer susceptibility to autoimmunity. The fact that more affected than unaffected relatives carried both the T and the R131 alleles simultaneously leads us to think about the existence of a combinatorial effect between genes that could help define individuals prone to autoimmune diseases.
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PMID:Multiplex family-based study in systemic lupus erythematosus: association between the R620W polymorphism of PTPN22 and the FcgammaRIIa (CD32A) R131 allele. 1709 57

Chronic deficiencies in the complement pathway proteins are associated with an increased risk of meningococcal disease. Such deficiencies are caused by primary congenital immunodeficiency of a complement protein, properdin or mannose binding lectin, or are secondary to consumption of complement by systemic lupus erythematosus (SLE) or membranoproliferative glomerulonephritis (MPGN). Whatever the cause, the complement deficiency is always chronic. Here we report a case of meningococcal disease (MCD) in a child with a transient complement deficiency (CD), caused by post-streptococcal glomerulonephritis (PSGN).
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PMID:Meningococcal disease associated with an acute post-streptococcal complement deficiency. 1729 26

Inherited deficiencies in components of the classical complement pathway are strong disease susceptibility factors for the development of systemic lupus erythematosus (SLE) and there is a hierarchy among deficiency states, the strongest association being with C1q deficiency. We investigated the relative importance of the different complement pathways regarding clearance of apoptotic cells. Phagocytosis of labelled apoptotic Jurkat cells by monocyte-derived macrophages in the presence of sera from individuals with complement deficiencies was studied, as well as C3 deposition on apoptotic cells using flow cytometry. Sera from individuals deficient in C1q, C4, C2 or C3 all showed decreased phagocytosis. Mannose binding lectin (MBL) and the alternative pathway did not influence phagocytosis. Notably, the components of the complement classical pathway, including C1q, were equally important in clearance of apoptotic cells. This indicates that deposition of C3 fragments is of major significance; we therefore studied C3 deposition on apoptotic cells. Experiments with MBL-deficient serum depleted of C1q or factor D confirmed the predominance of the classical pathway. At low dilution, sera deficient of C1q, C4 or C2 supported C3 fragment deposition demonstrating alternative pathway activation. In conclusion, we have found that complement-mediated opsonization and phagocytosis of apoptotic cells, particularly those undergoing secondary necrosis, are dependent mainly upon an intact classical pathway. The alternative pathway is less important, but may play a role in some conditions. C1q was not more important than other classical pathway components, suggesting a role in additional pathogenetic processes in SLE other than clearance of apoptotic cells.
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PMID:Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells. 1930 45

Mannose binding lectin (MBL) is an important element of the innate immune system. MBL binding leads to activation and cleavage of C3 and C4 suggesting the role of MBL pathway for opsonization and/ phagocytosis. The role of adaptive immune response in development of pathogenic autoantibodies in various autoimmune diseases is well understood. The link between innate and acquired immunity is helpful for understanding the immunopathogenesis of autoimmune diseases. Evidence that innate immune system could lead to autoimmunity is growing with the major recent concept of autoimmune disease pathogenesis is related to impaired apoptotic cell clearance. MBL have been demonstrated to facilitate clearance of apoptotic cells in vivo and in vitro. Low MBL serum levels resulting in impaired apoptotic clearance have shown to enhance the risk for infection and high MBL serum levels and high MBL activity have been associated with inflammatory autoimmune diseases like Systemic Lupus Erythematosus (SLE) that in turn results in to tissue damage and finally leads to organ damage. Serum MBL levels fluctuate during the course of SLE disease activity and MBL genotypes have been found to be useful in assessing the risk of infection during immunosuppressive treatment the majority of the SLE patients receive. This review focuses on the genetic and molecular characteristics of MBL and discusses MBL disease association in autoimmunity with special emphasis on SLE.
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PMID:Mannose binding lectin (MBL) in autoimmunity and its role in systemic lupus erythematosus (SLE). 2151 Apr 62

Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations.
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PMID:Mannose binding lectin gene (MBL2) functional polymorphisms are associated with systemic lupus erythematosus in southern Brazilians. 2151 Sep 92


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