Systemic Lupus Erythematosus SLE

SLE is a chronic autoimmune connective tissue disease characterized by inflammation and injury to the joints, tendons, and other connective tissues. Organs affected include the lungs, heart, blood vessels, brain, kidneys, and skin. SLE onset is associated with exposure to silica. Though earlier studies have suggested that organic solvent exposure can also be causative for SLE, more recent studies have refuted thisJ2,3,9 No literature references were found associating SLE onset with exposures to chemical mixtures. 

Exposures to toxic chemicals can adversely impact the bones as well as the soft tissues of the body. Osteoporosis and osteomalacia are two examples of this effect. 

Osteoporosis is a condition characterized by a loss of bone mass and density that has been causally related to exposure to cadmium, a toxic heavy metal that is widely distributed in the ambient environment. In a Chinese study, a dose-response relationship between cadmium exposure and osteoporosis was demonstrated. M Other studies have demonstrated that 

Osteomalacia is a condition in which the bones are softened because of impaired mineralization. Exposure to cadmium has been found to be causative for osteomalacia. 20,22,23 Other chemicals associated with osteomalacia are aluminum, lead, and fluoride. 24  

Only a very few studies have documented the toxic effects of chemical mixtures on the musculoskeletal system. Almost all of these studies address the effects of tobacco smoking and organic solvent exposure. The following studies are illustrative of those reported. 

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In infectious disease compounds such as ANA975 (phase I trials) and Resiquimod (phase II trails) have been developed to target Hepatitis C and genital herpes, respectively. DRS954 is a TLR-7 and 9 antagonist in pre-clinical trials for Systemic Lupus Erythematosus (SLE). 

Kilbum KH, Warshaw RH. 1992. Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. Environ Res 57 1-9. 

SLE Systemic lupus erythematosus SLe Sialyl Lewis X antigen SLO Streptolysin-O SLPI Secretory leucocyte protease inhibitor... 

OCs do not increase the risk of flare among women with stable systemic lupus erythematosus (SLE) and without antiphospholipid/anticardiolipin antibodies. 

Rheumatoid arthritis (RA), multiple sclerosis (MS) and systemic lupus erythematosus (SLE)... 

As a high incidence of arteriovenous thrombosis is described in patients with systemic lupus erythematosus (SLE), Matsuda et al. (Ml8) tried to demonstrate a relationship between the presence of anti-phospholipid antibodies and Lp(a) concentrations. They found that serum Lp(a) concentrations were increased in patients with SLE independent of the presence of anti-phospholipid antibodies. Borba et al. (B18) confirmed these findings and also could not correlate Lp(a) concentrations with anti-cardiolipid antibodies. 

Azathioprine is used in the treatment of several rheumatic diseases, including systemic lupus erythematosus (SLE) and RA. About 10-30% of RA patients discontinue AZA because of side effects (40). AZA is a prodrug that after oral intake is... 

Outcomes of in vitro methods or simple in vivo methods such as the PLNA, only indicate whether a compound can sensitize the immune system. They do not predict whether a compound can induce an autoimmune disease. For that disease models are warranted. However, most disease models, as mentioned, will often require predisposed animal strains such as systemic lupus erythematosus (SLE)-prone mice [81, 82]. Often models using autoimmune-prone mice or rats (including the BN rat) are considered too sensitive and are for that reason undesired by various stakeholders (i.e., pharmaceutical industries, regulatory agencies). 

The autoimmune rheumatic diseases consists of Rheumatoid Arthritis (RA), Spondylarthritis (SpA), Systemic Lupus Erythematosus (SLE), Polymyositis, Dermatomyositis, Polymyalgia Rheumatica, Acute Temporal Arteritis, Giant Cell Arteritis, Behcet s Disease, Sjorgren s Syndrome, Felty s Syndrome and Mixed Connective Tissue Disease (MCTD). Spondylarthritis (SpA) can be subdivided in Reactive Arthritis (ReA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Arthritis associated with the inflammatory bowel diseases are Crohn s disease and Ulcerative Colitis (IBD), Undifferentiated SpA (UspA) and Sacro-ilitis, Juvenile SpA and Acute Anterior Uveitis (AAU). 

The spectrum of Systemic Lupus Erythematosus (SLE) includes latent lupus, discoid lupus, drug-induced lupus, neonatal lupus, lupus profundus, neuropsychiatric lupus, lupus vasculitis, pulmonary lupus, etc. The disease course is characterized by unpredictable exacerbations, drug-induced remissions and spontaneous remissions. SLE is characterized by a wide range of variable individual clinical manifestations which are controllable at early stages. 

The drug hydralazine is a vasodilator used for the treatment of hypertension. In a significant proportion of individuals, it causes a serious adverse effect, drug-induced systemic lupus erythematosus (SLE). This is a systemic kind of toxic effect, as there is no particular target organ or tissue. It is an example of immune-media ted toxicity that involves autoimmunity and shows a number of interesting features. 

Naked pDNA delivery of cytokines has also been evaluated in a number of mouse models of autoimmune disease. Naked pDNA delivery of TGF/3 to a murine model of systemic lupus erythematosus (SLE) led to lower serum IgG levels, decreased glomerulonephritis and increased survival (Raz et al., 1995). The pDNA (100 gg) was injected i.m. at 6, 10, 14, 18 and 22 weeks. Administration of IL-2 encoding pDNA had the opposite effect, resulting in increased semm IgG, increased glomerulonephritis, and decreased survival, demonstrating that a disease course could be significantly modulated by naked pDNA therapy. The pDNA (100 gg) was injected once in every two weeks for a total of five injections. Circulating semm levels of either IL-2 or TGF 0 w ere detected up to two weeks after the final pDNA injection into the muscle. 

The anti-phospholipid syndrome refers to a range of autoimmune conditions which are characterised by venous or arterial thrombosis, recurrent strokes, pulmonary embolism, recurrent pregnancy loss or obstetric complications and the presence of circulating antibodies with specificity to a range of phospholipids including phosphatidylserine and cardiolipin. The syndrome is the leading cause of vascular thrombosis in children. It sometimes accompanies other autoimmune conditions such as systemic lupus erythematosus (SLE). 

Immunoadsorption, an advanced therapeutic modality, focuses on detoxification of patient blood rich in high-molecular-weight pathogenic substances, mostly abnormal autoantibodies such as rheumatoid factors in rheumatoid arthritis (RA) and anti-DNA autoantibodies in systemic lupus erythematosus (SLE). Detoxification of these pathogens will be accomplished through extracorporeal perfusion of the patient plasma or whole blood over an affinity column made of immunoadsorbents. These adsorbents perform their function through the same mechanism as conventional affinity adsorption, where proteins in the liquid phase are adsorbed on the specific ligands immobilized onto an insoluble support. 

A different approach to measuring EC damage has been circulating ECs (CECs). CECs have been described in patients with cardiovascular disease namely, in myocardial infarction [72], in unstable angina [73, 74], and postangioplasty [75]. In addition, CECs have also been found to be elevated in Rickettsia Conorii infection [76] and hematological disorders such as sickle cell disease [77, 78], TTP [79], and systemic lupus erythematosus (SLE) [80],... 

V3. Viallard, J. F., Pellegrin, J. L., Ranchin, V., Schaeverbeke, T., Dehais, J., Longy-Boursier, M., Ragnaud, J. M., Leng. B., and Moreau, J. F., Thl (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin. Exp. Immunol. 115, 189-195... 

Systemic lupus erythematosus (SLE) is a multisystemic disease characterized by a wide variety of autoantibodies leading to highly heterogeneous clinical manifestations. The target antigens of these autoantibodies include autoantigens in... 

L21. Lloyd, W., and Schur, P. H., Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus (SLE). Medicine (Baltimore) 60, 208-217 (1981). 

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