Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by self-reactive lymphocytes that mount an immune response against the body’s own tissues. It is an example of a type III hypersensitivity, which is linked with defects in the immune system’s ability to develop self-tolerance. The condition typically arises in the second decade of life and can give rise to a wide variety of symptoms which can cause both physical and psychological difficulties for those affected. Although there is no cure for the condition there are treatments available which can improve the quality of life for these patients.

Pathogenesis

1)      Environmental insults such as UV radiation lead to increased apoptosis of cells.

2)      Nuclear material leaks out of blebs on the surface of apoptotic cells. Defects in C1q of complement lead to inadequate clearance of circulating nuclear antigens, causing them to accumulate in the circulation.

3)      There are defects in self-tolerance, leading to the presence of self-reactive T and B cells.

4)      Dendritic cells with MHC capable of recognising self-antigen, uptake nuclear antigens and carry them to regional lymph nodes, where they present them to self-reactive lymphocytes. B cells are stimulated to produce autoantibodies against DNA.

5)      Complexes of antigen and antibody bind to Fc receptors on B cells and dendritic cells. They are internalised and antigen binds to intracellular TLRs (TLR7 and 9) which leads to the production of interferons and other cytokines (TNF-a, IL-10, IL-17, BAFF) which recruits more immune cells such as NK cells (which respond to IFN-a following viral infection) and sustains the inflammatory response and causes more apoptosis.

6)      The end result is a cycle of antigen release and immune activation, resulting in the production of high-affinity autoantibodies.

7)      Immune complexes accumulate and are deposited in organs, particularly those of high blood flow such as the joints and kidneys. Complement deposition induces the recruitment of cells such as neutrophils and mast cells which degranulate and damage local tissues. Chronic inflammation leads to the release of growth factors, which leads to fibrosis and widespread tissue damage.

People with SLE generate autoantibodies against many targets, such as double-stranded DNA, histones, red blood cells, platelets and phospholipids. These can cause many widespread symptoms.

–          Anti-RBC antibodies – Haemolytic anaemia

–          Anti-WBC antibodies – Leukocytopaenia

–          Anti-platelet antibodies – Thrombocytopaenia

–          Anti-phospholipid antibodies – vasculitis, arteriosclerosis which can lead to ischemia, stroke-like symptoms, cardiovascular disease

–          Specifically, anti-phospholipid antibodies can bind to prothrombin and paradoxically cause a hypercoaguable state which increases the likelihood of thrombus formation -> increased risk of stroke, miscarriage (eg. Anticardiolipin-Ab). In miscarriage, antibodies interfere with the growth and differentiation of trophoblasts leading to failure of placentation.

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