Systemic lupus erythematosus etiology

The prevalence and etiology of ectopic calcification due to alfacalcidol and associated susceptibility factors have been examined in 60 patients with systemic lupus erythematosus (13). The prevalence of ectopic calcification was 40%. Localization of calcification was in peripheral arteries (6.7%), in periarticular areas (33%), and in other soft tissues (17%). The incidence of lupus nephritis and nephrotic syndrome were significantly higher in those with ectopic calcification. Total protein concentrations (70 g/1) in patients with ectopic calcification were significantly lower than in patients without calcification (75 g/1). 

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. 

Nodular lymphoid hyperplasia BALT has replaced the term pseudolymphoma and is characterized by reactive lymphoid proliferation that characteristically shows numerous lymphoid follicles with large germinal centers usually occurring in middle-aged people, most of whom are asymptomatic. Approximately 10% to 15% of patients have a collagen vascular disease such as systemic lupus erythematosus or an immune disease of uncertain etiology, and they frequently exhibit polyclonal gam-mopathy. Polytypic plasma cells are common. Marker studies show a mixed population of CD4- and CD8-positive T cells. Most cases occur as solitary nodules and reoccur in up to 15% of surgically excised cases. 

There has been considerable interest in the role of Epstein-Barr virus in the etiology of several autoimmune diseases, particularly systemic lupus erythematosus and multiple sclerosis. Epstein-Barr virus is a common infection. Most people (90% or more) are infected, without symptoms or with only mild, nonspecific symptoms, during childhood. When people are exposed as teenagers or as adults, however, infection may result in mononucleosis. Of importance with respect to autoimmune diseases, Epstein-Barr virus infects B cells and results in a latent infection. A close similarity between a peptide sequence in the Epstein-Barr nuclear antigen-1 and a sequence in the Sm autoantigen, one of the autoantibodies seen in systemic lupus erythematosus, has been reported (Sabbatini et al., 1993). In addition, several epidemiological studies have demonstrated strong associations between exposure to Epstein-Barr virus, as demonstrated by virus-specific IgG or IgA antibodies, and risk of systemic lupus erythematosus in children (James et al., 1997) and adults (James et al., 2001 Parks et al., 2005). 

Sjogren syndrome. Chronic inflammatory autoimmune disease of the exocrine glands of unknown etiology. Its primary symptoms are keratoconjunctivitis sicca and xerostomia. Two types of Sjogren syndrome are distinguished a primary (isolated) type and a secondary type associated with another underlying autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, autoimmune hepatitis, multiple sclerosis, thyroiditis, autoimmune, etc.). Ro/SS-A and La/SS-B autoantibodies are used as classification criteria. 

James JA, Kaufman KM, Farris AD, Taylor-Albert E, Lehman TJ, Harley JB (1997) An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest, 100 3019-3026. 

There are a number of other diseases that have been associated with aberrations of serum thymic hormone bioactivity, and these are listed in Table 1. It is noteworthy that serum thymic hormone bioactivity has been found to be low in 25% to 50% of patients with systemic lupus erythematosus (Bach et al., 1975 Twomey et al., 1979 Iwata et al., 1981 Lewis et al., 1981), Hodgkin s disease (Schulof et al., 1981), and acute lymphoblastic leukemia (Twomey et al., 1980). In all of these studies it has not been possible to correlate abnormalities of serum thymic hormone bioactivity with specific defects of T cell immunity. Thus, it remains to be established whether low serum thymic hormone levels in autoimmune or neoplastic disorders reflect an etiologic role for thymus dysfunction in these disease processes or merely a secondary manifestation of the diseases themselves. In patients with acute lymphoblastic leukemia it was demonstrated that the low bioactivity detected in the Twomey assay was related to a circulating inhibitor of thymopoietinlike bioactivity (Twomey et al., 1980). Thus, it is possible that other secondary immunodeficiencies that are associated with depressed serum thymic-hormonelike bioactivity may also reflect the presence of circulating inhibitors to thymic hormones rather than an absolute deficiency in their production. 

The role of both T and B lymphocytes in a variety of disease states beyond transplantation has become increasingly important in the past decade. This is especially true of those diseases frequently referred to as autoimmune in their etiology, such as rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and so on. In addition, several other major diseases are also known to have a component of T- or B-cell-mediated pathogenesis, for example, atopic dermatitis, psoriasis, and asthma. Until very recently, the mainstay of therapy for these diseases was the corticosteroids, which were often less than satisfactory in efficacy and often associated with undesirable side effects, especially in growing children and the elderly. Thus, the search for new agents with different mechanisms of action and which did not have the same adverse event profile as conventional corticosteroids led to the subsequent evaluation of drugs such as tacrolimus and sirolimus to treat several of these diseases. 

James, J.A., Kaufman, KM., Farris, A.D., Taylor-Albert, E., Lehman, T.J., and Harley, J.B. (1997) An Increased Prevalence of Epstein-Barr Virus Infection in Young Patients Suggests a Possible Etiology for Systemic Lupus Erythematosus, J. Clin. Investig. 100,3019-3026. 

The connective tissue diseases (CTDs) are a heterogeneous group of immuno-logically mediated inflammatory conditions of unknown etiology, accompanied by diverse autoantibodies and affecting multiple organ systems. In adults, the more frequent CTDs comprise rheumatoid arthritis (RA), systemic sclerosis (SSc), Sjogren s syndrome (SjS), systemic lupus erythematosus (SLE), polymyositis/ dermatomyositis (PM/DM), and mixed CTD (MCTD). 

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