Systemic Lupus Erythematosus

Introduction
Systemic Lupus Erythematosus (SLE) is an autoimmune disease that composes many factors that contribute to the manisfestations of SLE. These factors include genetic and epigenetic regulation of gene expression, environmental factors, hormones, and a dysfunction in the immune system. It is estimated that about 1.5 million patients, and many other patients worldwide, have lupus. The survival rate of SLE patients improved from 50 % to 90% over the last 40 years from an estimated 5-year survival rate5. Managing SLE controls the disease activity and helps to prevent organ damage from therapeutic treatment and comorbidities associated with SLE disease.
Causes
The etiology of SLE is unknown, although in some cases, it tends to be hereditary.
Lupus is known to be mostly observed in young and middle aged women, frequently starting at childbearing age. Lupus is a multi-staged chronic inflammatory autoimmune disease that is not only defined by altered genes, but also by other contributing factors that trigger the disease.
Signs and Symptoms
Triggers of Systemic Lupus Erythematosus (SLE) symptoms include viral infection, too much sunlight, and some people showing signs and symptoms for an unknown reason.
There are some medicines that can cause lupus-like symptoms used to treat high blood pressure, abnormal heat rhythms, Chron’s disease, or rheumatoid arthritis. When these medications are stopped, the symptoms go away. Lupus symptoms varies in everyone who has Lupus. Some people with lupus experience skin rashes. The stages of the rash vary from mild to severe with crusty and round patches that can lead to scars or cause one’s hair to fall out. These symptoms include painful swollen joints, unknown cause of fever, sensitivity to sunlight, rash on the face, Raynaud’s phenomenon, fatigue, hair loss, swollen glands, memory loss or trouble concentrating, chest pain when you take a deep breath, high blood pressure, and nose or mouth sores. Patients with SLE can later experience cardiovascular diseases such as congestive heart failure. In addition, there are times where patients with SLE will not experience any signs and symptoms. This is called a remission. Less common symptoms of SLE include, anemia, headaches, seizures, depression, and
confusion.
Pathogenesis and Pathophysiology
Systemic Lupus Erythematosus (SLE) involves abnormalities of immune cells such as T and B cells, and Natural Killer (NK) cells. Natural Killer cells express CD56 and lack CD3 cells that are important for the innate immune response fighting against infections and tumors in the immune system.
According to Lin et al, there are two subsets of the human peripheral blood NK cells that have been identified to play an important in the immuno-regulatory system. These have been identified as CD56dim CD16+ NK subset, being more cytotoxic and CD56bright subset that have capability to produce a large amount of cytokines1. In addition to the association of the disease, genetic influences of SLE have been linked to abnormal gene expression from the histocompatibility complex class II alleles HLA-DR2 and HLA-DR3. This gene expression is known to be regulated by DNA methylation and histone modifications2.
Environmental factors include first and second hand smoking. A toxic chemical known as, Hydrazine, is found in cigarettes effecting the immune system by providing a phototoxic response which elevates the titers of the anti-double stranded DNA antibodies. Ultraviolet light causes keratinocytes of the skin to release special material that can stimulate the immune system and autoantibody production from B cells. In addition, Epstein-Barr virus (EBV) is known as an environmental factor to trigger SLE due to titers of IgA antibodies against the viral capsid antigen’s association with disease flares. Vaccines, psychological stress, silica dust, petroleum, nail polish, metal cleaners, dyes, and pesticides are also contributing factors associated with SLE.
Hormones such as estrogen and progesterone are also known to trigger SLE with the presence of the X chromosome. SLE is increased in men with Klinefelter’s syndrome and is decreased in women with Turner’s XO syndrome. The association of genes to the environment and hormones in the body lead to abnormal immune responses that generate pathogenic autoantibodies and immune complexes deposited into body tissues. Complement activation will then induce inflammation, leading to an irreversible organ damage.
Interleukin – (IL) 15 is a pleiotropic common gamma chain signaling cytokine important for activating CD8+ T cells and NK cells. It is known that IL-15 plays a crucial role in NK differentiation and survival. SLE patients have high serum levels of IL-15 where T and B lymphocytes in SLE patients responds to IL-15, upregulating surface CD25. SLE lymphocytes also respond to IL-15 due to the increase of their intracellular Bcl-23. Data shows some concern of TNF levels that are found in SLE patients are associated with their disease activity. M. Aringer et al suggested that IL-15 is not directly associated with SLE activity but can promote autoimmunity. Moreover, Interleukin-15 activates monocytes and macrophages and produces lymphocyte-dependent effects on autoantibodies and causes apoptosis followed by organ death.
Conclusion
Systemic Lupus Erythematosus (SLE) is a multi-staged autoimmune disease due to an unknown cause.
There are many factors that trigger to the disease such as abnormalities in immune cells and genes, environmental, and hormonal factors. Abnormalities of immune cells and gene occurs in the T and B cells, as well as, in NK cells. Abnormal gene expression is regulated by DNA methylation and histone modification. This chronic inflammatory disease can also be a disabling autoimmune disease that occurs on the face that follows a relapsing and remitting course. In trajectory, with longer expectancy rates, many patients suffering from Lupus have a higher chance of living longer due to better research, diagnostic techniques, and effective management of the
disease.