systemic lopus emosis or SLE for short is an autoimmune disease mediated by Auto antibodies and immune complexes which Target nearly every organ in the body SLE is a chronic multi-stem disorder that most commonly affects women during their reproductive years the pathophysiology of SLE involves injury to the body's own cells leading to damage cell proteins and their DNA injury to a group of cells can subsequently lead to organ injury the pathophysiology of SLE is thought to involve an interplay between genetics for example El is seen in mono zygotic twins and there's also influences of epigenetics Immunology factors hormonal factors such as estrogen and mainly environmental factors environmental factors is thought to be the initial trigger for SLE these environmental factors include UV light infection such as Epstein B virus smoking and even potentially certain drugs that increases oxidative stress damage that will lead to the cells being damaged damaged important to note that these environmental risk factors are agents which humans are commonly exposed to suggesting that people who develop SLE has to have some sort of genetic susceptibility when cells are damaged they can try to repair themselves if they can't they undergo programed cell death called apoptosis when cells undergo apoptosis internal proteins are displayed on their Sur surface blbs a normal response is when our immune system clears up these apoptotic cells this is done by phagocytes such as macrofagos and monocytes however if apoptotic cells are not cleared efficiently nuclear material is exposed to the immune system which may then become sensitized and eventually the immune system will mount an attack on our own proteins and nuclear material some people who develop SLE are seen to have deficiency in some complement proteins such as C1 C2 and C3 and C4 these proteins are important to help macrofagos clear up certain cells such as these apoptotic cells we mentioned earlier through opsonization for example deficiency in these early complement proteins mean apoptotic cells are not cleared effici efficiently when proteins and nuclear material are not cleared properly they are exposed to the immune system the immune system is start to become sensitized to these materials so next time they encounter such a material their body will mount an immune response towards their own proteins and nuclear material the process of sensitization begins when an immature antigen presenting cell such as an immature maccrage or dendritic cell notices and picks up proteins and nuclear material from the apoptotic cells through special receptors such as tolik receptor the antigen picked up by the antigen presenting cells include nuclear proteins cytoplasmic proteins and membrane components of the cell nuclear antigens include histone core double stranded DNA and ribonuclear protein complexes including SM n rnp and row cytoplasmic components also include row a small variant and cell membrane antigens including cardiol lipen found in mitochondria and may be platelet membranes or red blood cell membrane components as well regardless the antigens that are picked up by the antigen presenting cell are then displayed on the surface of the antigen presenting cell the antigens are presented to naive t- helper cells in nearby lymph nodes the naive t- helper when activated can become a number of different types of t- helper cells in the case of systemic lupus arthis where antibodies play the main role interlan 4 secreted favors t-h helper 2 cell maturation T helper 2 cells promotes the humoral immune response and so the antibody mediated immune response T helper 2 cells stimulate B Cell Activation and B cell proliferation activated B cells become plasma cells the cells responsible for producing the antibodies in this case oo antibodies which are the antibodies towards a person's own antigens remember the antibodies produced Target the antigens which the antigen presenting cell picked up such as the double stranded DNA the histone the SM the row the cardiol lipen therefore the antibodies produced are AO antibodies because they target self antigens most of these AO antibodies Target the nuclear proteins of the cells which are collectively known as Ana now these autoantibodies can also form immune complexes when exposed to their target antigens the antigen targeted are found in all cells and so these Auto antibodies can easily Target any cell in the body when the auto antibodies come in contact with nuclear proteins for example a few mechanisms of inflammation can occur firstly through immune complex formation and then deposition to organs resulting in complement activation augmenting the inflammatory response the immune complexes can bind onto FC receptors of immune cells which will trigger the release of pro-inflammatory cyto kindes promoting inflammation the Oto antibodies May bind on antigens on the cell surface or directly into the internal proteins resulting in complement activation and release of cyto from the cell finally the immune cells around the area are eventually sensitized to the antigens and so when the tolch recepta detects nuclear antigens for example they will release cyto kindes promoting the inflammation the inflam response these different mechanisms cause inflammation to the surrounding area causing further organ injury and damage this will further cause a Cascade of damaged cells and the cycle continues once the inflammation settles through the intrinsic regulation of the immune system the body will slowly recover however SLE is an ongoing chronic illness a feature of SLE are its flareups flareups or flares in SLE appears to reflect immunologic memory flare up occurs in response to another exposure of the antigen so really any precipitating factor that causes cell or mass cell apoptosis can trigger flareups and apoptosis exposes the nuclear materials to the immune cells precipitating factors include sun exposure infections stress surgery and pregnancy patients with SL generally have higher numbers of B cells plasma cells plasma blasts which are the immature plasma cells and higher proportions of activated t- cells than normal individuals cyto kindes which stimulate B Cell Activation include inter Lucan 6 and Inter Lucan 10 at least 50% of patients with have increased levels of B lymphocytic body production and differentiation into plasma cells risk factors for SLE is up to 20 times more common in women than men and most likely to develop between the ages of 15 to 40 years female sex is a risk factor due to the role of hormones which increases the susceptibility to develop SLE one characteristic of the immune response is the ability of our body to create immunological or immunologic memory that is memory immune cells that are ready to mount a response when they encounter the same antigen again flares in SLE as mentioned appear to reflect immunologic memory occurring in response to exposure of the antigens again the long lived plasma cells as the name suggests are plasma cells which live longer and typically reside in the bone marrow long- lived plasma cells can remember the same antigen when exposed to it again and begin secreting more AO antibodies to help finally to complete the diagram we talked about t helper 2 cells which help mount the humoral IM immune response then there's a t- helper one cells is the other arm of the t- helper activation however t- helper one cells promote the cell mediated immune response and so do not play a big role in the pathophysiology of SLE there are many signs and symptoms of SLE most complain of constitutional symptoms such as fatigue myalgia weight loss and fever the most common symptom or sign is a UV sensitive butterfly rash over the nasal bridge and malib Bones which occur in 50% of people individuals can also be sensitive to light the other cutaneous feature uh include discoid rash neurological involvement is very is common and include cognitive impairment which is very common headaches seizures uh which is and seizures are these uncontrolled electrical firing in the brain delirium and psychosis as well as peripheral neuropathies pulmonary involvement include interstitial fibrosis and Pulmonary vasculitis pulmonary puitis and plal fusions are seen in onethird of patients and are usually small cardiovascular involvement include pericardial disease which tend to be asymptom unless pericard Fusion becomes so big it will cause symptoms of chest pain and difficulty breathing asymptomatic myocarditis is also common and there's also risk of valvular heart disease hypertension is a common complication of slle and has to be well managed hypertension is probably due to uh complications of renal involvement seen in SLE renal involvement is seen in at least onethird of uh SLE patients and this is called lupus nephritis where the antibodies and the antibody complexes deposits at the glomerulus the functional units of the kidneys um and longterm this can lead to renal failure gastrointestinal involvement include these non-specific abdominal pain nausea vomiting that can be hepatomegaly and ulcerations as well which tend to be from medications hematological involvement occurs in about half the patients and include chronic anemia and leucopenia also can have complications uh from the immunosuppressive drugs used to treat asy which can also cause the same things muscular scal findings include arthralgia and arthritis which is common morning stiffness and polyarticular symmetrical arth arthis or arthritis occur in 90% of the cases patients with SLE can experience rods phenomenon which is an episodic power or sinosis of the fingers due to Vasa constriction of the arterials in the fingers in response to cold or emotional stress finally osteopenia and osteoporosis is important part of SLE and is a multifactorial cause in SLE which we will learn about later investigations for work up for SLE include a full blood count electrolyte Ura creatinine to look for kidney function lfts liver involvement and C r p ESR for inflammation a urine tests which involve urine analysis urine microscopy and urinary alamin cranin ratio is very important to monitor kidney function SLE serum markers must be ordered these serological markers are essentially antibodies detected against uh self antigens the antigens we discussed which include nuclear proteins cytoplasmic and cell membrane components these serologic iCal markers include antibodies against double stranded DNA you you can find anti-histamine anti-sm anti- row anti NR uh nrnp all these antibodies Target different nuclear proteins anti-nuclear antibody or Ana is another test to order which really encompasses all these antibodies Ana should be ordered in someone suspected of having s or any connective tissue disease then there's other tests such as Ena antii lipin an anti- rheumatoid Factor serum markers associated with disease flareups include reduced compliment 3 and complement four an increase in um anti-double stranded DNA remember to think about drug induced systemic lupus emosis for someone with no history of SLE someone who also recently began a new drug and has a positive uh Ana management of SLE involves just general principles such as avoiding UV light exposure vitamin D and calcium supplements reduce the cardiovascular risk through weight loss stop smoking stop alcohol and also managing the cholesterol now to understand how the pharmacological drugs help in SLE let's quickly revise the immune response again so remember antigen presenting cells presents a self antigen to to the t- helper cell interlan 2 is a cyto kind which stimulates t- helper activation and proliferation the interlukin four is one that helps uh produce T helper 2 cells which then activates and promotes B Cell Activation activated B cells become plasma cells which produce oo antibodies a whole Mark of SLE examples of pharmaceutical used inle include Tech which is a calci urine inhibitor inhibiting inter Lucan 2 production and function this will suppress T cell activity mop phenolate and as ayop purine are drugs which reduce lymphocyte activity both the B and T cells suppressing the immune system bab is a monoclonal antibody that blocks the B overexpressed in people with lupus promotes the survival and differentiation of B cells inhibiting it therefore aims to reduce antibody producing B cells during the inflammatory process in SLE specifically during the flare Ops immune cells and damaged cells release pro-inflammatory cyto kindes glucocorticoids are a main state for El and help suppress this inflammatory response nids are also useful especially for muscular scal pain associated with SLE controlled blood pressure as mentioned is important in SLE anti-hypertensives are therefore important the complications of SLE include osteoporosis and this is due to many factors low vitamin D from low sun exposure in patients with SLE renal osteodystrophy from renal impairment steroid use which increases risk of osteoporosis age and being female as low fluctuating estrogen levels increases the risks of osteoporosis other complications include antiphospholipid syndrome occurring in onethird of patients with SLE remember also that increases the risk of non- hodkin Loma