Patients with lupus produce abnormal antibodies in their blood that target tissues within their own body

rather than foreign infectious agents. Because the antibodies and accompanying cells of inflammation can affect tissues anywhere in the body, lupus has the potential to affect a variety of areas.

More recently, research has demonstrated evidence that a key enzyme's failure to dispose of dying cells may contribute the development of SLE. The enzyme, DNase1, normally eliminates what is called "garbage DNA" and other cellular debris by chopping them into tiny fragments for easier disposal. Researchers turned off the DNase1 gene in mice. The mice appeared healthy at birth, but after six to eight months, the majority of mice without DNase1 showed signs of SLE. Thus, a genetic mutation in a gene that could disrupt the body's cellular waste disposal may be involved in the initiation of SLE. An immune complex is the combination of an epitope with an
antibody directed against that epitope. The bound antigen and the binding antibody are referred to as a single entity in this state. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying C3b-receptors transport C3b-decorated immune complexes to the phagocytes, leave their charge there, mostly in liver and spleen, and return back to the general circulation. Immune complexes may themselves cause disease when they are deposited in organs, e.g. in certain forms of vasculitis. This is the third form of hypersensitivity in the Gell-Coombs classification, called Type III hypersensitivity.

Transmission
In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. SLE is triggered by environmental factors that are unknown. "All the key components of the immune system are involved in the underlying mechanisms" of SLE, according to Rahman, and SLE is the prototypical autoimmune disease. The immune system must have a balance (homeostasis) between being sensitive enough to protect against infection, and being too sensitive and attacking the body's own proteins (autoimmunity). From an evolutionary perspective, according to Crow, the population must have enough genetic diversity to protect itself against a wide range of possible infection; some genetic combinations result in autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus. Because of genetic variations in different components of the immune system, in some people the immune system attacks these nuclear-related proteins and produces antibodies against them. In the end, these antibody complexes damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins

they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links. [2][39][40] SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement.[41]

[edit] Abnormalities in apoptosis

Apoptosis is increased in monocytes and keratinocytes Expression of Fas by B cells and T cells is increased There are correlations between the apoptotic rates of lymphocytes and disease activity.

Tingible body macrophages (TBMs) are large phagocytic cells in the germinal centers of secondary lymph nodes; they express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation. In some people with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells that may have randomly acquired self-specificity through somatic hypermutation.[42]

[edit] Clearance deficiency

Clearance deficiency The exact mechanisms for the development of SLE are still unclear, since the pathogenesis is a multifactorial event. Beside discussed causation's, impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes deficient phagocytic activity and scant serum components in addition to increased apoptosis. Monocytes isolated from whole blood of SLE sufferers show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBM), which are found in the germinal centres of lymph nodes, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement factors, CRP, and some

glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient. The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens as well as internal danger signals, inducing maturation of dendritic cells (DC), since they have lost their membranes' integrity. Increased appearance of apoptotic cells also simulates inefficient clearance. That leads to maturation of DC and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules. Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE).