Disease autoimmune

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

Latex agglutination immunoassays are easily formatted into simple kits which can provide yes/no and semiquantitative estimates of antigen (or antibody) in a sample. The first such assay was developed in 1957 for rheumatoid factor (15) and assays are on the market for the deterrnination of many species of bacteria, fungi. Mycoplasma, parasites, ckettsia, and vimses, as well as for the deterrnination of autoimmune disease, hormones (qv), dmgs (see Pharmaceuticals), and blood proteins (16). Latex agglutination is also the basis of many home pregnancy tests. 

Immunosuppression induced by sirolimus (36) appears to be mediated by a mechanism distincdy different from that of either cyclosporin or FK-506. Sirolimus markedly suppresses IL-2 or IL-4-driven T-ceU proliferation. The preclinical studies suggest that sirolimus is a potent immunosuppressive agent in transplantation and autoimmune disease models. The clinical potential of this agent depends on its toxicity profile (80). 

Vitamin D metaboUtes may therefore play an active role ia diseases related to these functions, ie, leukemia, cancer (breast, colon, prostate), and autoimmune diseases (AIDS, immune encephaUtis, and diabetes) (51, 141,193—197, 202, 203). 

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

R. Schindler, ed.. Cyclosporin in Autoimmune Diseases, Springer-Vedag, Berlin, 1985. 

Organ specific autoimmune disease Constitutively activating somatic mutation in TSH... 

Part of these T-lymphocytes transform into memory cells. These cells are different from their ancestors in that they are activated by a much lower antigen binding strength and also much less depend on signal 2. Now self-antigens can activate these T-lymphocytes. As during activation continuously new memory cells are formed, autoreactivity is sustained and autoimmune disease follows (Fig. 2). 

Autoimmune Disease. Figure 1 Mechanisms of self tolerance. DC, dendritic (antigen presenting) cell T, T-lymphocyte Th, T helper lymphocyte Treg, T regulatory lymphocyte. For details see text. 

Autoimmune Disease. Figure 2 Generation of autoreactivity. APC, antigen presenting cell IFN, interferon LPS, lipopolysaccharide MHC, major histocompatibility complex T, T-lymphocyte TCR, Tcell (antigen) receptor TLR, toll like receptors. For details see text. 

Autoimmune diseases may inflict on each organ or cell. Manifestations range from affecting a single cell type and its specific function (such as the (3-cell of the islands in the pancreas) to systemic diseases which have a detrimental effect on an entire organ system (e.g. the vasculature) of even many different organs. Table 1 summarizes some clinically important diseases. 

Autoimmune Disease. Table 1 Autoimmune diseases Organ-specific autoimmune diseases... 

The treatment of an autoimmune disease very much depends on the nature of the clinical outcome it causes. Although the formation of autoantibodies causes the inactivation of the gastric intrinsic factor, the subsequent shortage of vitamin B12 can be easily overcome by supplying it via an parenteral route. Lifelong immunosuppression (with all its side effects) thus is inappropriate. When, however, as in sympathetic ophtalmia, after damage of the first eye the second eye is endangered, an even drastic immunosuppression is mandatory. 

As discussed above, the vast majority of autoimmune diseases is associated with chronic inflammation. The therapy thus rests on two principles ... 

Erdmann J, Fathman CG (2001) Autoimmune disease genes, bugs and failed regulation. Nat Immunol 9 759... 

Calcineurin is involved in cardiac hypertrophy and in cognitive and behavioral defects in the brain. Inhibitors of calcineurin such as cyclosporine A and FK 506 are used clinically in transplant rejection and autoimmune diseases. 

Inflammatory and immune diseases Autoimmune disease (A,I), asthma (A), osteoarthritis (I), rheumatoid arthritis (I), septic shock (A,I), infections (A,I), familial cold auto-inflammatory syndrome (I), Muckle Wells syndrome (I), chronic infantile neurological cutaneous and articular syndrome/neonatal onset multisystemic inflammatory disease (CINCA/NOMID) (I), Crohn s disease (I), gout (I), acute renal failure (A,l)... 

Pepin et al. (1992) generated transgenic mice in which antisense RNA complementary to GR cDNA led to reduced expression mostly in neuronal tissues. Consequently, this was found to result in an impaired behavior, a defective response to stress as well as in obesity. King et al. (1995) generated transgenic mice where reduced GR expression was limited to the thymus. This leads to an altered thymocyte development, changes in the T-cell repertoire, and a reduced risk to develop autoimmune diseases. 

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