Autoimmune disease systemic lupus erythematosus

Patients with the autoimmune disease systemic lupus erythematosus make autoantibodies directed against the Sm proteins of snRNP particles.552,553 Antibodies from different patients vary in tiieir specificities, making these antibodies a useful tool in the isolation and study of snRNAs and their protein complexes.552,554... 

A prime effect of ultraviolet radiation is on Langerhans cells in the skin, inducing them to leave the skin and affecting their functionality (Schwarz et al., 2000), resulting in dendritic cells that support tolerance rather than activation. Thus, ultraviolet radiation-induced damage in the skin plays a role in the stimulation of the autoimmune disease systemic lupus erythematosus. 

It has also been realized that histone modification patterns and levels are an important aspect when studying diseased gene expression states. For instance, it has recently been shown that certain aberrant posttranslational histone modifications are associated with the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) [381]. In this study, MS combined with stable isotope labeling was used to differentially analyze histone modifications in splenocytes from a mouse model of SLE. Compared to the control, the disease model showed a global site-specific hypermethylation, except for H3K4, and hypoacetylation in histone H3 and H4. 

One controlled, double-blind trial plus anecdotal evidence attest to the efficacy of chlorambucil in rheumatoid arthritis. Chlorambucil has also been used in Behef s disease, systemic lupus erythematosus, vasculitis, and other autoimmune disorders. 

There is also a significantly increased incidence of IgA deficiency in patients with autoimmune or potentially autoimmune disorders, and usually it is not clear which came first. It can be argued that autoimmunity is a complication of immune imbalance subsequent to inborn IgA deficiency (H24). With inborn absence of IgA, exposure to normal human colostrum, plasma, and saliva can result in the production of antibodies to IgA. By the time such patients are discovered the etiological mechanisms are often obscured and IgA treatment is out of the question. The incidence of IgA deficiency is known to be 1-4% in the following conditions Still s disease, systemic lupus erythematosus, rheumatoid arthritis, Sjogren s disease, warm hemolytic anemia, megaloblastic anemia, idiopathic pulmonary hemosiderosis, thyrotoxicosis, and cirrhosis. 

The interstitium of the kidney is also susceptible to injury from a variety of causes. Although acute interstitial nephritis is most commonly caused by medications (see Chap. 46), infections (e.g., streptococcal, leptospirosis, hantavirus, and human immimodeflciency virus), selected autoimmune disorders (systemic lupus erythematosus or mixed connective tissue disease) also may produce a similar syndrome. The presence of white blood cells (WBCs), WBC casts, and coarse granular casts in the urine aU suggest interstitial inflammation. The presence of eosinophUia and eosinophiluria also strongly suggest the presence of an interstitial nephritis. Occasionally low to moderate proteinuria can be seen on urinalysis. 

COPD, chronic obstructive pulmonary disease EAE, experimental autoimmune encephalomyelitis RSV, respiratory syncytial virus SLE, systemic lupus erythematosus. 

Besides anemia associated with cancer and CKD, anemia of chronic disease can result from inflammatory processes and occurs commonly in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. In treating these types of anemia of chronic disease, the most important principle is treating the underlying disease. These patients also may have iron deficiency and should be treated in the manner already discussed. Erythropoietin therapy such as epoetin-alfa therapy at a dose of 150 units/kg three times a week also may be used in these patients. 

Kovacic, P.J., J.D., Systemic lupus erythematosus and other autoimmune diseases from endogenous and exogenous agents unifying theme of oxidative stress, Mini Rev. Med Chem., 3, 568, 2003. 

Other studies describe similar beneficial effects for PUFA-enriched diets to treat Crohn s disease, other inflammatory bowel diseases such as ulcerative colitis, as well as psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis [57], Thus, immunomodulation by PUFAs appears to be a promising intervention for the treatment of many autoimmune and inflammatory diseases. 

McDonagh, J.E. and Isenberg, D.A., Development of additional autoimmune diseases in a population of patients with systemic lupus erythematosus, Ann. Rheum. Dis., 59, 230, 2000. 

A recent report by the National Institutes of Health estimated that at 14 to 22 million people in the United States are affected by an autoimmune disease.1 As a group, these diseases represent a leading cause of death among women under age 65, with systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes being the major sources of this impact on mortality.2 The autoimmune thyroid diseases, type 1 diabetes and rheumatoid arthritis are the most common of the autoimmune diseases (Table 25.1).3-5 Most autoimmune diseases disproportionately affect women. In the thyroid diseases, primary biliary cirrhosis, scleroderma, systemic lupus erythematosus, and Sjogren s syndrome, more than 85% of patients are female, but it is not known why the female predominance is so high in these specific diseases. 

For some autoimmune diseases, little is known about environmental factors involved in the initiation or progression of the disease. For other diseases, however, considerable research has been conducted on one or more types of exposures. Most epidemiologic studies of environmental influences have focused on multiple sclerosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and small vessel vasculitis, but experimental studies using murine models of these diseases is limited (Table 25.1). 

Strong mechanistic evidence from rodent models of autoimmune disease of viral or other infectious agents affecting autoimmunity or progression to overt disease, but harder to demonstrate in humans. Enterovirus (Coxsackie virus) focus of epidemiologic studies in type 1 diabetes, Epstein-Barr virus focus of epidemiologic studies in multiple sclerosis and systemic lupus erythematosus. 

Autoimmune disease There have been rare reports of various autoimmune diseases (eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis) in... 

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). 

Pathophysiologically, there is little difficulty in recognizing disseminated intravascular coagulation and then treating this on merit. Much more frequent are immunologically mediated mechanisms that may be secondary to underlying collagen-vascular diseases such as systemic lupus erythematosus or where the defect exists in isolation and the process is defined as primary, idiopathic or autoimmune. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

The main clinical uses of immunosuppressive drugs are suppression of organ and tissue rejection after transplant surgery and the treatment of diseases with an autoimmune component. Thses include renal diseases, e.g. glomerulonephritis, some nephrotic syndromes, connective tissue diseases, such as systemic lupus erythematosus rheumatoid arthritis, and systemic vasculitis. 

Azathioprine and mercaptopurine appear to be of definite benefit in maintaining renal allografts and may be of value in transplantation of other tissues. These antimetabolites have been used with some success in the management of acute glomerulonephritis and in the renal component of systemic lupus erythematosus. They have also proved useful in some cases of rheumatoid arthritis, Crohn s disease, and multiple sclerosis. The drugs have been of occasional use in prednisone-resistant antibody-mediated idiopathic thrombocytopenic purpura and autoimmune hemolytic anemias. 

---