Original Article
Mannose-Binding Lectin Variant Alleles and the Risk of Arterial Thrombosis in Systemic Lupus Erythematosus
N Engl J Med 2004; 351:260-267July 15, 2004
- Abstract
Background
Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated with an increased risk of arterial thrombosis among patients with SLE.
Methods
Mannose-binding lectin alleles were genotyped by means of a polymerase-chain-reaction assay in 91 Danish patients with SLE. Arterial and venous thromboses occurring after the diagnosis of SLE were assessed in a prospective study. Arterial and venous thromboses were confirmed by appropriate diagnostic methods.
Results
Fifty-four patients had no mannose-binding lectin variant alleles (A/A genotype), 30 were heterozygous (A/O genotype), and 7 were homozygous (O/O genotype). During a median follow-up of 9.1 years, arterial thromboses (cerebral or myocardial infarction or leg embolus) developed in 6 of the 7 patients with the O/O genotype, as compared with 18 of the 84 patients with the other two genotypes (hazard ratio, 5.8; 95 percent confidence interval, 2.2 to 15.2; overall incidence, 26 percent). After correction for other known risk factors, the hazard ratio was 7.0 (95 percent confidence interval, 1.9 to 25.4). Venous thromboses, which occurred in 14 patients, were statistically unrelated to the mannose-binding lectin genotype.
Conclusions
Among patients with SLE, homozygosity for mannose-binding lectin variant alleles is associated with an increased risk of arterial thrombosis. The risk of venous thrombosis is not increased, indicating that mannose-binding lectin has a specific role in providing protection against arterial thrombosis.
Media in This Article
Figure 1
Variations in Mannose-Binding Lectin Oligomerization, According to the Mannose-Binding Lectin (MBL2) Genotype.Figure 2
Cumulative Incidence of Arterial Thrombosis in 91 Patients with SLE, According to the Mannose-Binding Lectin Genotype.Article Activity
- Article
Cardiovascular disease is a major cause of illness and death in patients with systemic lupus erythematosus (SLE).1,2 Young patients with SLE are at substantially increased risk for coronary artery disease.3-5 The increased risk of cardiovascular disease in these patients is not fully accounted for by traditional atherosclerotic risk factors.6 However, several studies indicate that atherosclerosis is an active inflammatory and immune-mediated process7 and that this dyslipoproteinemia, which is characterized by high serum triglyceride levels and low serum levels of high-density lipoprotein, correlates with increased disease activity in patients with SLE.8 Factors modulating the inflammatory response in patients with SLE are therefore likely to be of interest with regard to the pathogenesis of cardiovascular disease in these patients.
Mannose-binding lectin is a liver-derived serum protein involved in innate immune defense. The ligands for mannose-binding lectin are mannose and N-acetyl glucosamine oligosaccharides, expressed by a wide range of microorganisms. Mannose-binding lectin may activate complement by means of the lectin pathway when interacting with mannose-binding lectin–associated serine proteases and can directly opsonize pathogens and enhance the activity of phagocytes by means of novel receptors.9 Serum mannose-binding lectin levels vary widely from person to person because of three variant alleles (B, C, and D, denoting the substitution of aspartic acid for glycine at codon 54, the substitution of glutamic acid for glycine at codon 57, and the substitution of cysteine for arginine at codon 52, respectively) in the structural moiety of the functional mannose-binding lectin gene, MBL2, located on chromosome 10 in humans.10 The normal allele is named A, and the common designation for the variant alleles is O. Each of the three variant alleles influences the stability of the final protein product, resulting in reduced serum levels and a dysfunctional mannose-binding lectin variant with a lower molecular weight than the normal protein.11 Moreover, base substitutions in the promoter region of the MBL2 gene have been shown to regulate the serum level of mannose-binding lectin.12 Specifically, in an otherwise structurally normal MBL2 gene, the substitution of C for G at position –221 (termed promoter allele X and resulting in haplotype XA) is associated with a low serum level of mannose-binding lectin.
Variant alleles causing low serum levels of functional mannose-binding lectin have been shown to be associated with an increased risk of infections13,14 and to alter the phenotypic expression of autoimmune diseases such as SLE15 and rheumatoid arthritis.16 However, patients with defects in mannose-binding lectin may also have atherosclerotic disease that has an earlier onset and is more severe than that in their counterparts with normal mannose-binding lectin.17 On the basis of our previous findings, we hypothesized that homozygosity for mannose-binding lectin variant alleles is associated with an increased risk of clinically detectable arterial thrombotic events in patients with SLE.
Methods
Patients
Consecutive, unrelated, white Danish patients with SLE were identified during 1996 and 1997 as previously described.15 The time of diagnosis of SLE was defined as the date when the American College of Rheumatology classification criteria18 for SLE were met. The study was approved by the local scientific ethics committee, and all patients provided written informed consent. Independent of mannose-binding lectin analyses, demographic and clinical data, including information on thromboses, were obtained from the clinical charts that were available from the time of diagnosis until June 2003 at the latest. The patients' race was determined by the investigators. The data-collection criteria were uniform for all patients.
Clinical Data
Clinical characteristics related to SLE have been described previously.15 Hypertension was defined as a blood-pressure measurement above 140/90 mm Hg alone or in combination with the need for antihypertensive medication sometime during the period of observation, but before the occurrence of any clinical outcomes. Patients were classified as never having smoked or as being former smokers or current smokers.
The primary clinical outcome in this study was arterial thrombosis, but data on venous thrombotic events were also collected to serve as thrombotic control events. Patients were considered to have arterial or venous thrombosis only when its presence was confirmed by appropriate diagnostic methods. The major clinical arterial manifestations included myocardial infarction (fatal and nonfatal), which was confirmed on the basis of elevated cardiac enzyme levels and electrocardiographic findings; cerebrovascular accident, which was confirmed on the basis of computed tomography, magnetic resonance imaging, or both; and peripheral arterial thrombosis, which was confirmed on the basis of arteriography. Deep-vein thrombosis was confirmed by means of Doppler studies, phlebography, or both, and pulmonary embolism was confirmed by means of ventilation–perfusion pulmonary scintigraphy.
Antiphospholipid Assays
Anticardiolipin antibodies were measured in serum samples at a dilution of 1:100. IgG and IgM anticardiolipin antibodies were quantitated by means of an enzyme-linked immunosorbent assay on polystyrene microtiter plates with the use of purified cardiolipin (Sigma) and bovine serum for blocking as described previously.19,20 Cutoff values for the anticardiolipin-antibody tests were 30 U per milliliter for IgM and 35 U per milliliter for IgG.19 Patients with a spontaneously prolonged partial-thromboplastin time were evaluated for lupus anticoagulant by mixing their plasma with normal plasma in a 1:1 ratio.21
Genotyping of Mannose-Binding Lectin
Genomic DNA was isolated from EDTA-treated blood cells and stored at –20°C.22 The mannose-binding lectin alleles were genotyped by means of the polymerase chain reaction with the use of sequence-specific priming.14,23 In exon 1 of the MBL2 gene, the presence of three single-base substitutions was investigated — at codon 54 (the B allele), codon 57 (the C allele), and codon 52 (the D allele).23-25 We also looked for down-regulating polymorphisms in the promoter region of the MBL2 gene: the substitution of the L allele for the H allele at position –550 and the substitution of the X allele for the Y allele at position –221.12 In addition, we determined the molecular structure of mannose-binding lectin in serum from six patients with SLE and different MBL2 genotypes through the use of immunologic affinity purification and subsequent sodium dodecyl sulfate–polyacrylamide-gel electrophoresis (3 to 8 percent Novex NuPAGE gradient gel, Invitrogen) and Western blotting as previously described.11
Statistical Analysis
First, we performed an unadjusted Cox proportional-hazards regression analysis to examine the relation between the presence of mannose-binding lectin genotype O/O and the risk of arterial thrombosis, venous thrombosis, or death among the 91 patients with SLE. Second, using multivariate Cox proportional-hazards regression analysis, we calculated the individual hazard ratios for arterial thrombosis with respect to the presence of mannose-binding lectin genotype O/O, lupus anticoagulant, IgG and IgM anticardiolipin antibodies, and hypertension; current or former smoking; male sex; and age at diagnosis (per decade). In these analyses, we examined the time from the diagnosis of SLE to a particular type of thrombotic event (arterial or venous), with data censored at the time of death or the end of follow-up, whichever came first. When we examined the time from diagnosis to death, data were censored only at the end of follow-up. Cumulative incidence estimates were plotted as a graphic representation of the risk of arterial thrombosis in the three genotype subgroups. All reported P values are two-sided, and P values of less than 0.05 were considered to indicate statistical significance.
Results
Ninety-one patients with SLE were included in the study.15 The total duration of follow-up was 1007 patient-years, and the median duration of disease was 9.1 years. The basic demographic, clinical, and serologic characteristics of the patients are shown in Table 1Table 1
Demographic, Clinical, and Serologic Characteristics of 91 Patients with Systemic Lupus Erythematosus.. Fifty-four (59 percent) of the patients had genotype A/A, 30 (33 percent) had genotype A/O, and 7 (8 percent) had genotype O/O. The distribution of the specific variant alleles in the heterozygous (A/O) patients was as follows: 16 were A/B, 3 were A/C, and 11 were A/D. The distribution of the specific variant alleles in the patients with the O/O genotype was as follows: one was B/C, five were B/D, and one was D/D, as previously reported.15 Of the 30 patients who were heterozygous, 8 (27 percent) carried the MBL2 promoter allele X, and 26 (87 percent) carried the promoter allele L on a functional A background. Figure 1Figure 1Variations in Mannose-Binding Lectin Oligomerization, According to the Mannose-Binding Lectin (MBL2) Genotype. shows that carriers of the O/O genotype lacked stable, high-molecular-weight forms of mannose-binding lectin in the blood, as compared with carriers of the A/O and A/A genotypes.During follow-up, arterial thrombosis occurred in 24 of the 91 patients (26 percent), and venous thrombosis occurred in 14 (15 percent) (Table 2Table 2
Incidence of Arterial and Venous Thrombotic Events and Death among 91 Patients with Systemic Lupus Erythematosus, According to the Mannose-Binding Lectin Genotype.). Ten patients died during follow-up; two of them had the O/O genotype and died after a myocardial infarction. During follow-up, there were 17 myocardial infarctions in 12 patients and 12 cerebral infarctions in 11 patients. This was equal to a yearly event rate of myocardial infarction and cerebral infarction of 2.9 percent (95 percent confidence interval, 1.9 to 4.1 percent). Venous thrombosis developed in 14 patients (15 percent).The risk of arterial thrombosis was significantly greater among patients with the O/O genotype than among those with the A/A or A/O genotype (hazard ratio, 5.8; 95 percent confidence interval, 2.2 to 15.2) (Table 2), mainly because of the strong association between the O/O genotype and myocardial infarction (hazard ratio, 9.4; 95 percent confidence interval, 2.6 to 33.7). The corresponding hazard ratio for cerebral infarction, 3.7, was not significant (P=0.10). There was no significant association between mannose-binding lectin variant alleles and venous thrombosis. The risk of death was greater among patients with the O/O genotype than among patients with one of the other two genotypes, but not significantly so. Among patients with the A/O or A/A genotype, the presence of the mannose-binding lectin promoter allele X or L was not significantly associated with arterial or venous thrombosis. Immunosuppressive therapy was not related to mannose-binding lectin genotypes15 or any of the thrombotic outcomes (data not shown).
Figure 2Figure 2
Cumulative Incidence of Arterial Thrombosis in 91 Patients with SLE, According to the Mannose-Binding Lectin Genotype. shows the cumulative incidence of arterial thrombosis in each of the three genotype subgroups and reveals a recessive effect of mannose-binding lectin variant alleles on the risk of arterial thrombosis. Cox regression analysis that included the O/O genotype, the age at diagnosis, male sex, the presence of lupus anticoagulant, current or former smoking, IgG anticardiolipin antibodies, IgM anticardiolipin antibodies, and hypertension showed that only the O/O genotype (hazard ratio as compared with the other two genotypes, 7.0; 95 percent confidence interval, 1.9 to 25.4; P=0.003) and the age at diagnosis (P=0.01) were associated with a significantly increased risk of arterial thrombosis (Table 3Table 3
Risk of Arterial Thrombosis among 91 Patients with Systemic Lupus Erythematosus.).Discussion
We found that homozygosity for mannose-binding lectin variant alleles is a major risk factor for arterial thrombosis in patients with SLE. Moreover, the increased thrombotic risk was specific for the arterial side of the circulation, since there was no significant association between mannose-binding lectin deficiency and venous thrombosis. The increased risk of thrombosis was particularly pronounced for myocardial infarction. This finding is in line with previous findings among patients with severe atherosclerotic coronary disease, who were four times as likely as control subjects to have the O/O genotype.17 In a large study of clinically healthy subjects, mannose-binding lectin variant alleles were associated with increased formation of atherosclerotic plaque in the carotid arteries,26 a finding that parallels our finding of an increased risk of stroke (albeit not significant) among patients with variant alleles. The relative weakness of the association between the O/O genotype and cerebral infarction may indicate that factors other than atherosclerosis are more important causes of this type of thrombotic event in patients with SLE.
We found no significant association between the risk of thrombosis and heterozygosity for mannose-binding lectin variant alleles (A/O), with or without reduced expression of a promoter allele on the functional chromosome (XA/O). Patients with the XA/O genotype have serum levels of mannose-binding lectin that are almost indistinguishable from those of patients with the O/O genotype.12 Using alternative detection systems, we recently showed that variant alleles give rise to detectable levels of circulating mannose-binding lectin.11 As we confirmed in the present study, however, variant mannose-binding lectin has less oligomerization and a lower molecular weight than normal mannose-binding lectin.11 Moreover, variant mannose-binding lectin has a reduced capacity to bind ligands and is dysfunctional. Thus, patients who are heterozygous for mannose-binding lectin variant alleles — even those with reduced expression of promoters — still have some normal mannose-binding lectin, whereas patients with the O/O genotype lack functional mannose-binding lectin, which probably explains the recessive phenotype we observed.
In our study, the annual rate of myocardial infarction and stroke was 2.9 percent overall (95 percent confidence interval, 1.9 to 4.1 percent), which overlaps the corresponding figure of 2.0 percent reported in a similar study, from Canada, of atherosclerosis in patients with SLE.6 The relation between premature atherosclerosis and SLE is clinically well described but cannot be fully accounted for by traditional risk factors. We found the expected association between arterial thrombosis and increasing age, but not between arterial thrombosis and hypertension — a finding that differs from that of the Canadian study.6 However, our use of a dichotomous classification of hypertension may have led to a loss of discriminative power. Also, we did not find a significant association between arterial thrombosis and antiphospholipid antibodies. However, the hazard ratios with respect to lupus anticoagulant and IgG anticardiolipin antibodies were higher than the hazard ratio with respect to IgM anticardiolipin antibodies, which is in line with previous findings in two separate cohorts of patients with SLE.27 In previous studies of patients with SLE, smoking has been found to have a variable effect on the risk of arterial thrombosis.6,28,29 In our study, former or current smoking was not associated with a significantly increased risk of arterial thrombosis in patients with SLE. Unfortunately, we were unable to account for lipid status; this information was not recorded systematically because the trial was not primarily designed as a study of cardiovascular outcomes. Other factors that have been found to be associated with arterial thrombosis in patients with SLE include signs of complement activation and corticosteroid treatment.28 In our cohort, none of the immunosuppressive treatments used were related to arterial thrombosis.
Women with SLE have an increased prevalence of carotid and femoral plaque that is not accounted for by other predictors of atherosclerosis, such as age, lipid status, and the cumulative dose of corticosteroids.29 Many of these SLE-related atherosclerotic risk factors are related to increased disease activity; a recent study has corroborated these findings and, furthermore, has demonstrated an association between carotid plaque and disease-related damage.30 Some studies have shown that mannose-binding lectin variant alleles are associated with increased disease activity in patients with SLE31 and with signs of increased inflammation in patients with rheumatoid arthritis or giant-cell arteritis.16,32
Therefore, the possibility that part of the atherosclerotic risk associated with mannose-binding lectin deficiency is attributable to the extent of disease activity cannot be ruled out. However, as previously stated in a description of this cohort of patients, the mannose-binding lectin genotypes were not associated with clinical characteristics specific for SLE or treatment regimens that reflect increased disease activity or severity.15
Several other mechanisms may underlie the atherogenic effect of mannose-binding lectin deficiency. A well-described effect of mannose-binding lectin deficiency is an increased risk of infection, which has also been described in patients with SLE.15,31 A number of studies have indicated an association between infections in general, and Chlamydia pneumoniae infection in particular, and coronary artery disease, although this remains controversial.33 In a controlled study of 210 patients, C. pneumoniae infection and coronary artery disease were associated, but only in patients with mannose-binding lectin variant alleles.34 Whether patients with SLE have an increased prevalence of previous infection with C. pneumoniae needs further exploration.
The accumulation of lipid material is unquestionably important in atherogenesis, but why this material accumulates and is not cleared by phagocytic cells, such as macrophages, is not well understood. Defective clearance of apoptotic endothelial cells may be of importance in this context. It is therefore of particular interest that mannose-binding lectin binds to and sequesters apoptotic and damaged host cells.35 A reverse effect of mannose-binding lectin has been suggested in experimental models of ischemic reperfusion injury after myocardial infarction, since mannose-binding lectin may initiate complement activation central to the pathophysiology of this condition.36
In the general population, mannose-binding lectin deficiency is unlikely to be particularly dangerous, except during the vulnerable period of infancy, when the immune system is immature.13 However, the deficiency may represent a threat to patients with complex conditions such as cystic fibrosis, which involve both genetic and acquired dysfunctions,37 or SLE, in which more than one of the above-described pathogenetic mechanisms may be operative and even act synergistically with traditional atherosclerotic risk factors.
In conclusion, we found that homozygosity for mannose-binding lectin variant alleles significantly increased the risk of arterial thrombosis in a cohort of patients with SLE. This thrombotic effect, which was not seen in the venous side of the circulation, may indicate a specific role for mannose-binding lectin in protecting against atherosclerosis. The compelling and strong association between mannose-binding lectin deficiency and arterial thrombotic events in patients with SLE indicates the need for mannose-binding lectin genotyping to guide future prophylactic initiatives in these and other patients at high risk for cardiovascular disease.
Supported by the Danish Rheumatism Association, the Danish Medical Research Council, the Novo Nordisk Research Foundation, and a grant (QLGI-CT-2001-01039) from the European Union.
We are indebted to Ms. Bente Frederiksen and Ms. Vibeke Weirup for excellent technical assistance.
Source Information
From the Department of Rheumatology, Bispebjerg Hospital (T.Ø., S.J.); the Department of Rheumatology, Hvidovre Hospital (T.Ø., S.J.); and the Department of Rheumatology (T.Ø., S.J.) and the Tissue Typing Laboratory, Department of Clinical Immunology (T.Ø., P.G., H.O.M.), Rigshospitalet, University of Copenhagen — all in Copenhagen, Denmark.
Address reprint requests to Dr. Jacobsen at the Department of Rheumatology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark, or at sj@dadlnet.dk.
- References
References
1
Jacobsen S ,Petersen J ,Ullman S , et al. A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value. Clin Rheumatol 1998;17:478-484
CrossRef | Web of Science | Medline2
Cervera R ,Khamashta MA ,Font J , et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003;82:299-308
CrossRef | Web of Science | Medline3
Ward MM . Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 1999;42:338-346
CrossRef | Web of Science | Medline4
Thorburn CM ,Ward MM . Hospitalizations for coronary artery disease among patients with systemic lupus erythematosus. Arthritis Rheum 2003;48:2519-2523
CrossRef | Web of Science | Medline5
Asanuma Y ,Oeser A ,Shintani AK , et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003;349:2407-2415
Full Text | Web of Science | Medline6
Esdaile JM ,Abrahamowicz M ,Grodzicky T , et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2002;44:2331-2337
CrossRef | Web of Science7
Kao AH ,Sabatine JM ,Manzi S . Update on vascular disease in systemic lupus erythematosus. Curr Opin Rheumatol 2003;15:519-527
CrossRef | Web of Science | Medline8
Svenungsson E ,Gunnarsson I ,Fei GZ ,Lundberg IE ,Klareskog L ,Frostegard J . Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor alpha/tumor necrosis factor receptor system in systemic lupus erythematosus. Arthritis Rheum 2003;48:2533-2540
CrossRef | Web of Science | Medline9
Turner MW ,Hamvas RMJ . Mannose-binding lectin: structure, function, genetics and disease associations. Rev Immunogenet 2000;2:305-322
Medline10
Madsen HO ,Garred P ,Kurtzhals JAL , et al. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. Immunogenetics 1994;40:37-44
CrossRef | Web of Science | Medline11
Garred P ,Larsen F ,Madsen HO ,Koch C . Mannose-binding lectin deficiency -- revisited. Mol Immunol 2003;40:73-84
CrossRef | Web of Science | Medline12
Madsen HO ,Garred P ,Thiel S , et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995;155:3013-3020
Web of Science | Medline13
Koch A ,Melbye M ,Sorensen P , et al. Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. JAMA 2001;285:1316-1321
CrossRef | Web of Science | Medline14
Garred P ,Strom J ,Quist L ,Taaning E ,Madsen HO . Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J Infect Dis 2003;188:1394-1403
CrossRef | Web of Science | Medline15
Garred P ,Madsen HO ,Halberg P , et al. Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus. Arthritis Rheum 1999;42:2145-2152
CrossRef | Web of Science | Medline16
Jacobsen S ,Madsen HO ,Klarlund M , et al. The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. J Rheumatol 2001;28:935-942
Web of Science | Medline17
Madsen HO ,Videm V ,Svejgaard A ,Svennevig JL ,Garred P . Association of mannose-binding-lectin deficiency with severe atherosclerosis. Lancet 1998;352:959-960
CrossRef | Web of Science | Medline18
Tan EM ,Cohen AS ,Fries JF , et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-1277
CrossRef | Web of Science | Medline19
Mouritsen S ,Hoier-Madsen M ,Wiik A ,Orum O ,Strandberg Pedersen N . The specificity of anti-cardiolipin antibodies from syphilis patients and from patients with systemic lupus erythematosus. Clin Exp Immunol 1989;76:178-183
Web of Science | Medline20
Loizou S ,McCrea JD ,Rudge AC ,Reynolds R ,Boyle CC ,Harris EN . Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp Immunol 1985;62:738-745
Web of Science | Medline21
Brandt JT ,Triplett DA ,Alving B ,Scharrer I . Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995;74:1185-1190
Web of Science | Medline22
Miller SA ,Dykes DD ,Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215-1215
CrossRef | Web of Science | Medline23
Garred P, Madsen HO, Svejgaard A. Genetics of human mannan-binding protein. In: Ezekowitz RAB, Sastry K, Reid KBM, eds. Collectins and innate immunity. Austin, Tex.: R.G. Landes, 1996:139-64.
24
Sumiya M ,Super M ,Tabona P , et al. Molecular basis of opsonic defect in immunodeficient children. Lancet 1991;337:1569-1570
CrossRef | Web of Science | Medline25
Lipscombe RJ ,Sumiya M ,Hill AV , et al. High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet 1992;1:709-715[Erratum, Hum Mol Genet 1993;2:342.]
CrossRef | Medline26
Hegele RA ,Ban MR ,Anderson CM ,Spence JD . Infection-susceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area. J Investig Med 2000;48:198-202
Web of Science | Medline27
Voss A ,Jacobsen S ,Heegaard NH . Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia. Lupus 2001;10:533-538
CrossRef | Web of Science | Medline28
Manger K ,Kusus M ,Forster C , et al. Factors associated with coronary artery calcification in young female patients with SLE. Ann Rheum Dis 2003;62:846-850
CrossRef | Web of Science | Medline29
Vlachoyiannopoulos PG ,Kanellopoulos PG ,Ioannidis JPA ,Tektonidou MG ,Mastorakou I ,Moutsopoulos HM . Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Rheumatology 2003;42:645-651
CrossRef | Web of Science | Medline30
Roman MJ ,Shanker BA ,Davis A , et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003;349:2399-2406
Full Text | Web of Science | Medline31
Garred P ,Voss A ,Madsen HO ,Junker P . Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients. Genes Immun 2001;2:442-450
CrossRef | Web of Science | Medline32
Jacobsen S ,Baslund B ,Madsen HO ,Tvede N ,Svejgaard A ,Garred P . Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis. J Rheumatol 2002;29:2148-2153
Web of Science | Medline33
Danesh J ,Whincup P ,Lewington S , et al. Chlamydia pneumoniae IgA titres and coronary heart disease: prospective study and meta-analysis. Eur Heart J 2002;23:371-375
CrossRef | Web of Science | Medline34
Rugonfalvi-Kiss S ,Endresz V ,Madsen HO , et al. Association of Chlamydia pneumoniae with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin. Circulation 2002;106:1071-1076
CrossRef | Web of Science | Medline35
Nauta AJ ,Raaschou-Jensen N ,Roos A , et al. Mannose-binding lectin engagement with late apoptotic and necrotic cells. Eur J Immunol 2003;33:2853-2863
CrossRef | Web of Science | Medline36
Collard CD ,Vakeva A ,Morrissey MA , et al. Complement activation after oxidative stress: role of the lectin complement pathway. Am J Pathol 2000;156:1549-1556
CrossRef | Web of Science | Medline37
Garred P ,Pressler T ,Madsen HO , et al. Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest 1999;104:431-437
CrossRef | Web of Science | Medline
- Citing Articles (74)
Citing Articles
1
Angelica B.W. Boldt, Isabela Goeldner, Iara J.T. de Messias-Reason. 2012. Relevance of the lectin pathway of complement in rheumatic diseases. , 105-153.
CrossRef2
Costantino Iadecola, Josef Anrather. (2011) Reply to: Mannose-binding lectin—the forgotten molecule?. Nature Medicine 17:12, 1548-1548
CrossRef3
Paula Sandrin-Garcia, Lucas André Cavalcanti Brandão, Antônio Victor Campos Coelho, Rafael Lima Guimarães, João Alexandre Trés Pancoto, Ludovica Segat, Eduardo Antônio Donadi, José Luiz de Lima-Filho, Sergio Crovella. (2011) Mannose binding lectin gene (MBL2) functional polymorphisms are associated with systemic lupus erythematosus in southern Brazilians. Human Immunology 72:6, 516-521
CrossRef4
Tang Yongqing, Nicole Drentin, Renee C. Duncan, Lakshmi C. Wijeyewickrema, Robert N. Pike. (2011) Mannose-binding lectin serine proteases and associated proteins of the lectin pathway of complement: Two genes, five proteins and many functions?. Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics
CrossRef5
Roberta Gualtierotti, Martina Biggioggero, Pier Luigi Meroni. (2011) Cutting-Edge Issues in Coronary Disease and the Primary Antiphospholipid Syndrome. Clinical Reviews in Allergy & Immunology
CrossRef6
Arash Alipour, Manuel Castro Cabezas, Jan Willem F. Elte, Joan-Carles Vallvé, Josep Ribalta, Aeilko H. Zwinderman, Joep C. Defesche, J. Wouter Jukema. (2011) Mannose binding lectin 2 haplotypes do not affect the progression of coronary atherosclerosis in men with proven coronary artery disease treated with pravastatin. Atherosclerosis 215:1, 125-129
CrossRef7
Margherita Zen, Nicola Bassi, Carla Campana, Silvano Bettio, Elena Tarricone, Linda Nalotto, Anna Ghirardello, Andrea Doria. (2010) Protective molecules and their cognate antibodies: new players in autoimmunity. Autoimmunity Highlights 1:2, 63-72
CrossRef8
V. Scalzi, H. Abu Hadi, C. Alessandri, C. Croia, V. Conti, L. Agati, A. Angelici, V. Riccieri, C. Meschini, A. Al-Motarreb, A. Al-Ansi, G. Valesini. (2010) Anti-endothelial cell antibodies in rheumatic heart disease. Clinical & Experimental Immunology 161:3, 570-575
CrossRef9
Kathryn E McDougal, Deanna M Green, Lori L Vanscoy, M Daniele Fallin, Michael Grow, Suzanne Cheng, Scott M Blackman, J Michael Collaco, Lindsay B Henderson, Kathleen Naughton, Garry R Cutting. (2010) Use of a modeling framework to evaluate the effect of a modifier gene (MBL2) on variation in cystic fibrosis. European Journal of Human Genetics 18:6, 680-684
CrossRef10
M. Trendelenburg, P. Theroux, A. Stebbins, C. Granger, P. Armstrong, M. Pfisterer. (2010) Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. European Heart Journal 31:10, 1181-1187
CrossRef11
T.F. Mendonça, M.C.V.C. Oliveira, L.R.S. Vasconcelos, L.M.M.B. Pereira, P. Moura, M.A.C. Bezerra, M.N.N. Santos, A.S. Araújo, M.S.M. Cavalcanti. (2010) Association of variant alleles of MBL2 gene with vasoocclusive crisis in children with sickle cell anemia. Blood Cells, Molecules, and Diseases 44:4, 224-228
CrossRef12
Lawrence T. Lai, Daniel C. Lee, Wilson Ko, Ketan Shevde, Ming Zhang. (2010) Deficiency of complement factor MBL in a patient required cardiac surgery after an acute myocardial infarction with underlining chronic lymphocytic leukemia. International Journal of Cardiology 139:2, e24-e26
CrossRef13
Marietta Charakida, Ann E. Donald, Sam Leary, Julian P. Halcox, Malcolm W. Turner, Marina Johnson, Stavros P. Loukogeorgakis, Michael I. Okorie, George Davey Smith, John E. Deanfield, Nigel J. Klein. (2010) Endothelial response to childhood infection: The role of mannose-binding lectin (MBL). Atherosclerosis 208:1, 217-221
CrossRef14
Sibel Zehra Aydin, Pamir Atagunduz, Burak Erer, Cengiz Bahadir, Nevsun Inanc, Haner Direskeneli. (2010) Mannose binding lectin levels are not related to radiographic damage in ankylosing spondylitis. Rheumatology International 30:3, 415-417
CrossRef15
Jeremy B.M. Jowett. (2010) Interplay of genetic and environmental factors: Innate immunity genetic polymorphisms in MBL2 affect endothelial dysfunction and risk of atherosclerosis. Atherosclerosis 208:1, 32-33
CrossRef16
Lone N. Troelsen, Peter Garred, Buris Christiansen, Christian Torp-Pedersen, Ib J. Christensen, Eva Narvestad, Søren Jacobsen. (2010) Double role of mannose-binding lectin in relation to carotid intima–media thickness in patients with rheumatoid arthritis. Molecular Immunology 47:4, 713-718
CrossRef17
Paula I Burgos, Graciela S Alarcón. (2009) Thrombosis in systemic lupus erythematosus: risk and protection. Expert Review of Cardiovascular Therapy 7:12, 1541-1549
CrossRef18
Gaëlle Le Friec, Claudia Kemper. (2009) Complement: coming full circle. Archivum Immunologiae et Therapiae Experimentalis 57:6, 393-407
CrossRef19
A. Alipour, A.J.H.H.M. van Oostrom, J.P.H. Van Wijk, C. Verseyden, H.W.M. Plokker, J.W. Jukema, A.J. Rabelink, M. Castro Cabezas. (2009) Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in normolipidemic subjects. Atherosclerosis 206:2, 444-450
CrossRef20
H. David Pettigrew, Suzanne S. Teuber, M. Eric Gershwin. (2009) Clinical Significance of Complement Deficiencies. Annals of the New York Academy of Sciences 1173:1, 108-123
CrossRef21
I Kim, Y J Kim, K Kim, C Kang, C-B Choi, Y-K Sung, H-S Lee, S-C Bae. (2009) Genetic studies of systemic lupus erythematosus in Asia: where are we now?. Genes and Immunity 10:5, 421-432
CrossRef22
R.A. Matthijsen, J.P.M. Derikx, R. Steffensen, R.M. van Dam, C.H.C. Dejong, W.A. Buurman. (2009) Mannose-binding lectin null alleles are associated with preserved epithelial cell integrity following intestinal ischemia reperfusion in man. Molecular Immunology 46:11-12, 2244-2248
CrossRef23
Tomomitsu Tahara, Tomoyuki Shibata, Fang-Yu Wang, Masakatsu Nakamura, Hiromi Yamashita, Daisuke Yoshioka, Masaaki Okubo, Naoko Maruyama, Yoshio Kamiya, Masahiko Nakamura, Hiroshi Fujita, Mitsuo Nagasaka, Masami Iwata, Kazuya Takahama, Makoto Watanabe, Hiroshi Nakano, Ichiro Hirata, Tomiyasu Arisawa. (2009) Mannan-binding lectin B allele is associated with a risk of developing more severe gastric mucosal atrophy in Helicobacter pylori-infected Japanese patients. European Journal of Gastroenterology & Hepatology 21:7, 781-786
CrossRef24
Daniel L. Worthley, Douglas F. Johnson, Damon P. Eisen, Melinda M. Dean, Susan L. Heatley, John‐Paul Tung, Justin Scott, Robert T. A. Padbury, Hugh A. Harley, Peter G. Bardy, Peter W. Angus, Charles G. Mullighan. (2009) Donor Mannose‐Binding Lectin Deficiency Increases the Likelihood of Clinically Significant Infection after Liver Transplantation. Clinical Infectious Diseases 48:4, 410-417
CrossRef25
Milena Ivanova, Ju Ruiqing, Masaki Matsushita, Takahiro Ogawa, Shintaro Kawai, Naoya Ochiai, Velizar Shivarov, Etsuko Maruya, Hiroh Saji. (2008) MBL2 single nucleotide polymorphism diversity among four ethnic groups as revealed by a bead-based liquid array profiling. Human Immunology 69:12, 877-884
CrossRef26
M. Ramos-Casals, P. Brito-Zeron, N. Soria, N. Nardi, A. Vargas, S. Munoz, A. Bove, B. Suarez, F. Lozano. (2008) Mannose-binding lectin-low genotypes are associated with milder systemic and immunological disease expression in primary Sjogren's syndrome. Rheumatology 48:1, 65-69
CrossRef27
Fang-Yu Wang, Tomomitsu Tahara, Tomiyasu Arisawa, Tomoyuki Shibata, Hiromi Yamashita, Masakatsu Nakamura, Daisuke Yoshioka, Masaaki Okubo, Naoko Maruyama, Toshiaki Kamano, Yoshio Kamiya, Masahiko Nakamura, Hiroshi Fujita, Mitsuo Nagasaka, Masami Iwata, Kazuya Takahama, Makoto Watanabe, Hiroshi Nakano, Ichiro Hirata. (2008) Mannan-binding Lectin (MBL) Polymorphism and Gastric Cancer Risk in Japanese Population. Digestive Diseases and Sciences 53:11, 2904-2908
CrossRef28
Maria Gerosa, Cecilia Chighizola, Pier Luigi Meroni. (2008) Aspirin in asymptomatic patients with confirmed positivity of antiphospholipid antibodies? Yes (in some cases). Internal and Emergency Medicine 3:3, 201-203
CrossRef29
Sahena Haque, Hoda Mirjafari, Ian N Bruce. (2008) Atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Current Opinion in Lipidology 19:4, 338-343
CrossRef30
Odirlei André Monticielo, Tamara Mucenic, Ricardo Machado Xavier, João Carlos Tavares Brenol, José Artur Bogo Chies. (2008) The role of mannose-binding lectin in systemic lupus erythematosus. Clinical Rheumatology 27:4, 413-419
CrossRef31
Alanna C Morrison, Eric Boerwinkle, Stephen T Turner, Robert E Ferrell. (2008) Regional Association-based Fine-mapping for Sodium–Lithium Countertransport on Chromosome 10. American Journal of Hypertension 21:1, 117-121
CrossRef32
L. Jakab, J. Laki, K. Sallai, Gy. Temesszentandrási, T. Pozsonyi, L. Kalabay, L. Varga, T. Gombos, B. Blaskó, A. Bíró, H.O. Madsen, J. Radics, P. Gergely, G. Füst, L. Czirják, P. Garred, B. Fekete. (2007) Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene. Clinical Immunology 125:3, 230-236
CrossRef33
P. L. MERONI, F. PEYVANDI, L. FOCO, L. BERNARDINELLI, R. FETIVEAU, P. M. MANNUCCI, A. TINCANI, . (2007) Anti-beta 2 glycoprotein I antibodies and the risk of myocardial infarction in young premenopausal women. Journal of Thrombosis and Haemostasis 5:12, 2421-2428
CrossRef34
Martin Soubrier, Sylvain Mathieu, Jean-Jacques Dubost. (2007) Atheroma and systemic lupus erythematosus. Joint Bone Spine 74:6, 566-570
CrossRef35
Hee Jung Kang, Sun-Mi Lee, Hyeon-Hwa Lee, Ji Yeon Kim, Byung-Chul Lee, Jung-Sun Yum, Hong Mo Moon, Bok Luel Lee. (2007) Mannose-binding lectin without the aid of its associated serine proteases alters lipopolysaccharide-mediated cytokine/chemokine secretion from human endothelial cells. Immunology 122:3, 335-342
CrossRef36
Jamal Mikdashi. (2007) Inflammation, dyslipidemia and risks of ischemic strokes in systemic lupus erythematosus. Future Lipidology 2:5, 489-493
CrossRef37
Steffen Thiel. (2007) Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Molecular Immunology 44:16, 3875-3888
CrossRef38
Jessica Konstantou, Penelope C. Ioannou, Theodore K. Christopoulos. (2007) Genotyping of single nucleotide polymorphisms by primer extension reaction and a dual-analyte bio/chemiluminometric assay. Analytical and Bioanalytical Chemistry 388:8, 1747-1754
CrossRef39
Andrea Baccarelli, Lifang Hou, Paolo Grillo, Wong-Ho Chow. (2007) Reply to the letter to the Editor:Helicobacter pylori infection andMBL2 haplotypes: Lack of association or lack of evidence?. International Journal of Cancer 120:12, 2750-2750
CrossRef40
Lone Troelsen, Peter Garred, Hans O. Madsen, Søren Jacobsen. (2007) Reply. Arthritis & Rheumatism 56:6, 2097-2098
CrossRef41
Mary C. Walsh, Lisa A. Shaffer, Benjamin J. Guikema, Simon C. Body, Stanton K. Shernan, Amanda A. Fox, Charles D. Collard, Michael Fung, Ronald P. Taylor, Gregory L. Stahl. (2007) Fluorochrome-linked immunoassay for functional analysis of the mannose binding lectin complement pathway to the level of C3 cleavage. Journal of Immunological Methods 323:2, 147-159
CrossRef42
Sander I. van Leuven, Erik S. G. Stroes. (2007) Mannose-binding lectin and agalactosyl IgG and risk of ischemic heart disease in rheumatoid arthritis: Comment on the article by Troelsen et al. Arthritis & Rheumatism 56:6, 2097-2097
CrossRef43
Bevra H. Hahn, Jennifer Grossman, Weiling Chen, Maureen McMahon. (2007) The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: Roles of inflammation and dyslipidemia. Journal of Autoimmunity 28:2-3, 69-75
CrossRef44
Grith L. Sorensen, Inge Petersen, Steffen Thiel, Mogens Fenger, Kaare Christensen, Kirsten O. Kyvik, Thorkild I. A. Sørensen, Uffe Holmskov, Jens Christian Jensenius. (2007) Genetic influences on mannan-binding lectin (MBL) and mannan-binding lectin associated serine protease-2 (MASP-2) activity. Genetic Epidemiology 31:1, 31-41
CrossRef45
Lone N. Troelsen, Peter Garred, Hans Ole Madsen, Søren Jacobsen. (2007) Genetically determined high serum levels of mannose-binding lectin and agalactosyl IgG are associated with ischemic heart disease in rheumatoid arthritis. Arthritis & Rheumatism 56:1, 21-29
CrossRef46
Jean Sibilia. (2006) Treatment of systemic lupus erythematosus in 2006. Joint Bone Spine 73:6, 591-598
CrossRef47
Yuta KOCHI, Kenichi SHIMANE, Kazuhiko YAMAMOTO. (2006) The genetics of systemic lupus erythematosus: differences across ethnicities. APLAR Journal of Rheumatology 9:4, 353-358
CrossRef48
Iara Jose Messias Reason, Marcelo Derbi Schafranski, Jens Christian Jensenius, Rudi Steffensen. (2006) The Association Between Mannose-Binding Lectin Gene Polymorphism and Rheumatic Heart Disease. Human Immunology 67:12, 991-998
CrossRef49
Andrea Baccarelli, Lifang Hou, Jinbo Chen, Jolanta Lissowska, Emad M. El-Omar, Paolo Grillo, Sara M. Giacomini, Meredith Yaeger, Toralf Bernig, Witold Zatonski, Joseph F. Fraumeni, Stephen J. Chanock, Wong-Ho Chow. (2006) Mannose-binding lectin-2 genetic variation and stomach cancer risk. International Journal of Cancer 119:8, 1970-1975
CrossRef50
R. M. Dommett, N Klein, M. W. Turner. (2006) Mannose-binding lectin in innate immunity: past, present and future. Tissue Antigens 68:3, 193-209
CrossRef51
Olaf A. Bodamer, Georg Mitterer, Wolfgang Maurer, Arnold Pollak, Manfred W. Mueller, Wolfgang M. Schmidt. (2006) Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth. Genetics in Medicine 8:8, 518-524
CrossRef52
Jaime Calvo-Alén, Graciela S. Alarcón, Monty B. Tew, Filemon K. Tan, Gerald McGwin, Barri J. Fessler, Luis M. Vilá, John D. Reveille, . (2006) Systemic lupus erythematosus in a multiethnic US cohort: XXXIV. Deficient mannose-binding lectin exon 1 polymorphisms are associated with cerebrovascular but not with other arterial thrombotic events. Arthritis & Rheumatism 54:6, 1940-1945
CrossRef53
H Terence Cook, Marina Botto. (2006) Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nature Clinical Practice Rheumatology 2:6, 330-337
CrossRef54
Ana M. Bertoli, Mónica Fernández, Gerald McGwin, Graciela S. Alarcón, Filemon K. Tan, John D. Reveille, Luis M. Vilá. (2006) Systemic lupus erythematosus in a multiethnic US cohort: XXXVI. Influence of mannose-binding lectin exon 1 polymorphisms in disease manifestations, course, and outcome. Arthritis & Rheumatism 54:5, 1703-1704
CrossRef55
Lee H. Bouwman, Bart O. Roep, Anja Roos. (2006) Mannose-Binding Lectin: Clinical Implications for Infection, Transplantation, and Autoimmunity. Human Immunology 67:4-5, 247-256
CrossRef56
Esther J. Pavón, Pilar Muñoz, Antonio Lario, Victoria Longobardo, Montserrat Carrascal, Joaquín Abián, Ana B. Martin, Salvador A. Arias, José-Luis Callejas-Rubio, Ricardo Sola, Francisco Navarro-Pelayo, Enrique Raya-Alvarez, Norberto Ortego-Centeno, Mercedes Zubiaur, Jaime Sancho. (2006) Proteomic analysis of plasma from patients with systemic lupus erythematosus: Increased presence of haptoglobin α2 polypeptide chains over the α1 isoforms. PROTEOMICS 6:S1, S282-S292
CrossRef57
Panayotis G. Zerefos, Penelope C. Ioannou, Joanne Traeger-Synodinos, Gerasimos Dimissianos, Emmanuel Kanavakis, Theodore K. Christopoulos. (2006) Photoprotein aequorin as a novel reporter for SNP genotyping by primer extension–application to the variants of mannose-binding lectin gene. Human Mutation 27:3, 279-285
CrossRef58
S. Thiel, P.D. Frederiksen, J.C. Jensenius. (2006) Clinical manifestations of mannan-binding lectin deficiency. Molecular Immunology 43:1-2, 86-96
CrossRef59
A.G. Sjöholm, G. Jönsson, J.H. Braconier, G. Sturfelt, L. Truedsson. (2006) Complement deficiency and disease: An update. Molecular Immunology 43:1-2, 78-85
CrossRef60
Reiko Takahashi, Akito Tsutsumi, Katsuki Ohtani, Nobutaka Wakamiya, Takayuki Sumida. (2005) Lack of relationship between mannose-binding lectin variant alleles and risk of arterial thrombosis in Japanese patients with systemic lupus erythematosus. Modern Rheumatology 15:6, 459-460
CrossRef61
C. C. MOK. (2005) Can survival of systemic lupus erythematosus be further improved?. APLAR Journal of Rheumatology 8:3, 159-164
CrossRef62
Young Ho Lee, Torsten Witte, Tanja Momot, Reinhold E. Schmidt, Kenneth M. Kaufman, John B. Harley, Andrea L. Sestak. (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: Two case-control studies and a meta-analysis. Arthritis & Rheumatism 52:12, 3966-3974
CrossRef63
Martine Szyper Kravitz, Milena Pitashny, Yehuda Shoenfeld. (2005) Protective Molecules–C-Reactive Protein (CRP), Serum Amyloid P (SAP), Pentraxin3 (PTX3), Mannose-Binding Lectin (MBL), and Apolipoprotein A1 (Apo A1), and Their Autoantibodies: Prevalence and Clinical Significance in Autoimmunity. Journal of Clinical Immunology 25:6, 582-591
CrossRef64
Rikke Sørensen, Steffen Thiel, Jens C. Jensenius. (2005) Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Springer Seminars in Immunopathology 27:3, 299-319
CrossRef65
B. Fevang, T. E. Mollnes, A. M. Holm, T. Ueland, L. Heggelund, J. K. Damas, P. Aukrust, S. S. Froland. (2005) Common variable immunodeficiency and the complement system; low mannose-binding lectin levels are associated with bronchiectasis. Clinical and Experimental Immunology 0:0, 051018021550004
CrossRef66
Sander I van Leuven, John JP Kastelein, Michael R Hayden, David dʼCruz, Graham R Hughes, Erik S Stroes. (2005) Cardiovascular disease in systemic lupus erythematosus: has the time for action come?. Current Opinion in Lipidology 16:5, 501-506
CrossRef67
D. L. Worthley, P. G. Bardy, C. G. Mullighan. (2005) Mannose-binding lectin: biology and clinical implications. Internal Medicine Journal 35:9, 548-555
CrossRef68
Chi Chiu Mok, Sandy Shuk Kuen Tang, Chi Hung To, Michelle Petri. (2005) Incidence and risk factors of thromboembolism in systemic lupus erythematosus: A comparison of three ethnic groups. Arthritis & Rheumatism 52:9, 2774-2782
CrossRef69
Sahena Haque, Ian N Bruce. (2005) Therapy Insight: systemic lupus erythematosus as a risk factor for cardiovascular disease. Nature Clinical Practice Cardiovascular Medicine 2:8, 423-430
CrossRef70
G??ran J??nsson, Lennart Truedsson, Gunnar Sturfelt, Vivi-Anne Oxelius, Jean Henrik Braconier, Anders G. Sj??holm. (2005) Hereditary C2 Deficiency in Sweden. Medicine 84:1, 23-34
CrossRef71
Lieve Nuytinck, Fred Shapiro. (2004) Mannose-binding lectin: laying the stepping stones from clinical research to personalized medicine. Personalized Medicine 1:1, 35-52
CrossRef72
Laura E. Schanberg, Christy Sandborg. (2004) Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus. Current Rheumatology Reports 6:6, 425-433
CrossRef73
(2004) Arterial Thrombosis in Systemic Lupus Erythematosus. New England Journal of Medicine 351:18, 1910-1911
Full Text74
Peter Garred, Hans O. Madsen. (2004) Genetic susceptibility to sepsis: A possible role for mannose-binding lectin. Current Infectious Disease Reports 6:5, 367-373
CrossRef
- Letters
