Systemic lupus erythematosus. N Engl J Med

Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom.
New England Journal of Medicine (Impact Factor: 54.42). 03/2008; 358(9):929-39. DOI: 10.1056/NEJMra071297
Source: PubMed

ABSTRACT Pathogenic autoantibodies are the primary cause of tissue damage in patients with lupus. The production of these antibodies arises by means of complex mechanisms involving every key facet of the immune system. Many different elements of the system are potential targets for therapeutic drugs in patients with lupus.

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    • "It can lead to enhanced processing and presentation of selfantigens, which induces the expansion or spreading of immune response toward different selfantigens (Gershwin 2008; Sfriso et al. 2010). SLE is a multifactorial systemic autoimmune disorder which affects multiple organs including the skin, lung, joints, kidneys, and heart (Rahman and Isenberg 2008). The cause of SLE is unknown, however many abnormalities in cellular and humoral immune responses including autoantibody production by dysregulated B cells, aberrant immune cell activation due to abnormal antigen presenting cells (APC) function, and autoantigen production have been reported in SLE patients (Steinberg 1992; Wozniacka et al. 2006). "
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    ABSTRACT: Although many patients with SLE also have allergies, the immunological events triggering the onset and progression of the clinical manifestations of SLE by allergens have yet to be clarified. A total of three autoantigens, phosphoglycerate kinase 1 (PGK-1), triosephosphate isomerase (TIM) and enolase were identified by autologous serum in B cell lysate derived from HDM allergic SLE patients after Der p 2 stimulation. Autoantigen, TRIM-21 expression were also significantly increased in B cells derived from HDM allergic SLE patients. In PBMCs derived from SLE patients, the concentration of anti-PGK-1 was significantly upregulated after Der p 2 stimulation compared to HDM allergic without SLE patients and healthy subjects. Inflammatory related cytokines and chemokines include IL-1β, IL-6, IL-8, CXCL5 could be upregulated after Der p 2 stimulation in PBMCs derived from HDM allergic SLE patients. In conclusion, our data demonstrated that long-term allergen exposure could be a contributing factor in the development of SLE.
    Immunobiology 08/2014; 219(12). DOI:10.1016/j.imbio.2014.07.018 · 3.18 Impact Factor
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    • "Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to progressive end-organ damage and is characterized by the presence of autoantibodies directed against nuclear and cytoplasmic antigens [1] [2] [3]. Globally, the incidence rate of SLE varies from 1 to 10 per 100,000 person-years and the prevalence rate varies from 20 to 70 per 100,000 person-years [4]. "
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    ABSTRACT: Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF functions in a positive feedback loop with TNF-α that could perpetuate the inflammatory process in systemic lupus erythematosus (SLE). In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with SLE as well as with MIF and TNF- α serum levels in a Mexican-Mestizo population. Genotyping of the -794CATT5-8(rs5844572) and -173G>C(rs755622) MIF polymorphisms was performed by PCR and PCR-RFLP respectively in186 SLE patients and 200 healthy subjects. MIF and TNF- α serum levels were determined by ELISA. A significant increase of MIF and TNF- α levels was found in SLE patients. According to a genetic model, we found a significant association of genotypes carrying the -794CATT7 and -173∗C risk alleles with susceptibility to SLE and with a significant increase of TNF-α. In conclusion, MIF gene polymorphisms are associated with SLE susceptibility and with an increase of TNF-α serum levels in a Mexican-Mestizo population.
    Human immunology 05/2014; DOI:10.1016/j.humimm.2014.02.014 · 2.28 Impact Factor
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    • "Anti-Ro60 (Ro60) and anti-Ro52 (Ro52) autoantibodies are associated with different clinical situations [3]. The former is clearly associated with systemic lupus erythematosus (SLE) [4] and Sjögren's syndrome (SS) [5], whereas the clinical significance of Ro52 is more wide-ranging. More than 10 years ago Ro52 was found to be associated with idiopathic inflammatory myopathy (IIM) [6], and since then it has also been related with other autoimmune diseases [7] [8]. "
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    ABSTRACT: Anti-Ro52 (Ro52) and anti-Ro60 (Ro60) antibodies are associated with different clinical entities. We investigated their relationship with the presence of anti-SS-B/La (SSB) antibody, the pattern and titer of antinuclear antibody (ANA), and the variations in antibody profiles related with anti-SS-A/Ro (SSA) positivity. Our aim was to develop a strategy to increase the efficiency of anti-extractable nuclear antigen (ENA) determinations. Statistical analyses were based on the chi-squared test for categorical variables, the Mann-Whitney U test to compare profiles, and the odds ratio (OR) and 95% confidence interval (95% CI) to estimate the risk of variability. We analyzed 800 SSA-positive samples with Ro52 or Ro60 reactivity. The most frequent profiles were Ro52+Ro60+SSB (n=349, 43.6%); Ro52+Ro60 (n=126, 15.8%); Ro52 (n=121, 15.1%) and Ro60 (n=71, 8.9%). In samples positive only for SSA and an ANA titer ≤1:640, the most likely profile was positivity for either Ro52 or Ro60, whereas when the ANA titer was >1:640, positivity for both Ro52 and Ro60 simultaneously was more likely (p<0.001). In samples positive for both SSA and SSB, the most likely profile was Ro52+Ro60+SSB regardless of the ANA titer (p=0.001). When only SSA was positive and the ANA staining pattern was nucleolar, centromeric or cytoplasmic, Ro52 positivity was most likely (p<0.001). When both SSA and SSB were positive, both Ro52 and Ro60 were likely to be positive regardless of the ANA staining pattern. In 28.7% of the patients the profile was variable. Variability was significantly greater in those with the SSA profile (23/67) than with the SSA+SSB profile (15/105; OR=1.9 95% CI=1.1-3.3; p=0.025), and the difference in variability was greatest between the Ro52+Ro60 profile (8/23) and the Ro52+Ro60+SSB profile (8/68; OR=4.2 95% CI=1.9-9.5; p<0.001). We conclude that to increase efficiency in the immunology laboratory, positivity for Ro52 and Ro60 individually or simultaneously can be deduced from SSB status and the ANA pattern and titer. In general, for the most frequent anti-ENA findings, priority should be given to retesting autoantibodies not detected in the initial analysis.
    Immunology letters 04/2014; 161(1). DOI:10.1016/j.imlet.2014.04.009 · 2.37 Impact Factor
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