The Phenomenon of Autoimmunity Dissertation Introduction

The phenomenon of autoimmunity was first described by Paul Ehrlich. He named it as horror autotoxicus. He explained that the immune system functions in recognizing foreign particles and mounting immunity against them. The immune system in its normalcy has the ability to differentiate between self and non-self molecules, and mounts immunity only against non-self molecules. When this balance goes wrong, autoimmune diseases occur (Bell and Bird, 2005). Autoimmune diseases are of two types, systemic and organ specific. Systemic lupus erythematosus is an example of a systemic autoimmune disease while diabetes mellitus is an example of an organ-specific autoimmune disease. Autoimmunity is a diseased condition where the immune system develops auto-antibodies to self-molecules. Autoimmune diseases are linked to various genetic factors. Some autoimmune diseases are caused due to mutations in a single gene. Examples are lymphoproliferative syndrome and polyglandular endocrinopathy with candidiasis and ectodermal dysplasia. However, many autoimmune diseases occur as a result of abnormalities in more than one gene, i.e. they are multigenic (Davidson and Diamond, 2001). There have been three main approaches to study autoimmune diseases. These are candidate gene analysis, linkage analysis and genome-wide association studies. Genome-wide association studies (GWAS) pose a novel and efficient technology to study autoimmune diseases and has revealed the complexity of such diseases by enlightening us of the underlying pathogenicity. Currently there are more than 80 autoimmune diseases known and various genes have been associated with them. Such studies have revealed different classes of genes like tyrosine phosphotases, tumor necrosis factor receptor and pattern recognition receptors that are associated with autoimmune diseases (Gregersen and Olsson, 2008). The links of autoimmune diseases with other pathogenic conditions like cancer and chronic inflammatory conditions further enhance their complexity. Recent studies have suggested that autoimmunity is a risk factor for the development of malignancy, and that some cancer can lead to the development of autoimmune diseases Franks and Slansky, 2012). A study conducted in 1998 suggested that patients with lupus, an autoimmune disease have increased risks of cancer. The glutathione S-transferases or GSTs are a family of proteins that catalyze the metabolism of potentially toxic compounds. Some genotypes of GSTs have been associated in autoimmune diseases like lupus. Interestingly, GSTs have also been associated with breast cancer. Women without the GSTM1 gene were found to have a double-fold risk for developing breast cancer whereas those without the GSTT1 gene were found to have a 1.5 fold risk (Volkers, 1999). A study conducted in mouse models found a relationship between autoimmune arthritis and breast cancer. Breast cacner survival was found to be lower in patients who also had autoimmune arthritis. The study found a relationship between mast cells and malignant metastatic tumors. Mast cells are immune cells that are responsible for inflammation. It had already been established in mouse models that metastases associated with breast cancer were more frequent and potent in mice with autoimmune arthritis than in control mice without arthritis in bone and lung cancer. Further study suggested that the number of mast cells is higher in arthritic mice when compared to non-arthritic controls. The present study suggests that there is a possible connection between a receptor called cKit receptor found on mast cells and the transmembrane stem cell factor (SCF) ligand found on metastatic breast cancer cells. In vivo interaction between the two proteins was found to have a direct role in cancer metastasis and malignancy. The study used two kinds of mice, one with spontaneous arthritis (SKG mice) and the other with spontaneous breast cancer (MMTV-PyV MT mice). The study pointed out that the number of mast cells in bone and lung of the mice with arthritis and breast cancer was higher than those without arthritis and breast cancer. The expression of SCF in breast cancer cells regulates the differentiation of mast cells from bone marrow. These mast cells in turn regulate the metastasis breast cancer to other areas, especially bone and lung (Roy et al, 2013). It has also been reported that there is a correlation between thyroid autoimmunity and breast cancer. In a study that analyzed thyroid autoimmunity in 102 patients with ductal infiltrating carcinoma, it was found that the incidence of thyroid autoimmunity was increased in patients with breast cancer. Further studies were conducted to correlate autoimmunity and breast cancer with lymphocytic infiltrates. However, lymphocytic infiltration was found to have no role in the connection of autoimmunity and breast cancer (Fibberacci et al, 2006). Likewise, patients with cancer have also been found to have increased risk for autoimmune diseases

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