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Flashcards in Lupus Deck (41):
1

definition of systemic lupus erythematosus

a systemic autoimmune disease characterized by the production of antibodies to the components of a cell nucleus in association with protean clinical manifestations

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criteria for SLE

>4 criteria fulfilled. Must have at least one clinical and one lab OR biopsy proven lupus nephritis with positive ANA or anti-DNA

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clinical criteria for SLE

malar rash, discoid rash, oral/nasal ulcers, non-scarring alopecia, arthritis, serositis, renal, neurologic, hemolytic anemia, thrombocytopenia, leucopenia

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immunologic criteria for SLE

ANA (anti nuclear antibody), anti-dsDNA, Anti-Smith, anti phospholipid antibodies, low complement levels (C3,4), positive direct coombs test

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malar rash

acute cutaneous lupus, butterfly rash die to photosensitivity. Cheeks and nose. Non-scarring.

6

Discoid lupus

chronic cutaneous lupus, red raised disc shaped patches. can be anywhere on body. scarring.

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alopecia in lupus

diffuse thinning or hair fragility with visible broken hairs, in the absence of other causes

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arthritis in lupus

tends to be non-erosive (jacoud's: erosion of MC heads and ulnar deviation)

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serositis in lupus

inflammation around the lining of the lung or heart that causes chest pain when taking a deep breath. Lung=pleuritis, heart=pericarditis

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nephritis in lupus

protein in urine (>500mg/24hrs) &/or red cell casts

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red cell casts

red cells from the glomerulus of the kidney surrounded by a proteinacious matrix, indicative of inflammation and damage to the kidney

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neurologic symptoms of lupus

seizures, psychosis, myelitis (cerebritis)

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hematologic symptoms of lupus

hemolytic anemia (coombs positive), leukopenia or lymphopenia, thrombocytopenia

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lupus epidemiology

females:male=15:1, can present at any age. children/men tend to be more severe, uncommon in europeans/africans,

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why are women more affected by lupus?

X chromosome may contribute? pregnant lupus patients have less of an estrogen/progesterone surge during late trimesters, UNKNOWN

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genetics of lupus

cumulative effect of several genes is necessary, very heterogenous

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environmental factors for lupus

viruses like EBV (molecular mimicry?), UV light (increased cytokines?), smoking

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autoantibodies

antibodies that recognize self antigens generated during antibody assembly and pass through defective check point system. LOSS OF SELF TOLERANCE

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pathway of self antigen presentation

APCs are hyper activated by environmental, viral or other trigger, so they phagocytose self antigen and are activated. They then present self-antigen to host lymphocytes which should have been killed during development

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ANA

anti-nuclear antibodies that bind to antigens found in the nucleus of the cell.

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how to measure ANAs?

indirect immunofluorescence & ELISA. HEp2 cells are coated with patient serum and Ab:Ag complexes are detected via anti-human fluorescence labeled antibodies. Serial dilutions tested to determine titer volume of antibodies

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HEp2 cells

immortalized laryngeal epidermoid carcinoma cells

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anti dsDNA

specific for SLE and titer fluctuates with disease activity. associated with active glomerulonephritis, perinuclear ANA fluorescent pattern

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Anti Smith (SM)

specific for SLE, Speckled ANA fluorescent pattern

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anti-RNP

seen in both SLE and mixed connective tissue disease

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Anti-Ro/La (SSA/SSB)

seen in SLE and with Sjogrens Syndrome and pathogenic in neonatal lupus.

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antiphospholipid antibodies

antibody to phospholipid part of cell membrane thought to make blood more susceptible to clotting, causing clots in arteries, veins, and increased risk of miscarriage

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possible pathogenic mechanisms for SLE

apoptosis, immune complex deposition, cytokine production, T cells

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abnormal apoptosis in SLE

self antigens are normally recognized when cells apoptose, but in SLE phagocytosis and IC clearing is defective due to deficient Fc and complement receptors

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when do nuclear antigens present?

appear within apoptotic blebs or are released during blebbing. impaired phagocytosis leads to persistence of antigen and immune complexes

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apoptotic blebbing

main phagocytic targets

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neonatal lupus

mother's anti-Ro/La crosses the placenta and gets into the fetal circulation and binds fetal myocardiocyte after blebs containing Ro antibody are exposed, causing inflammation and cell death. manifests as conduction abnormality and causes death in utero.

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immune complex deposition

IC activates complement system, which causes recruitment of inflammatory cells, IC gets phagocytosed and additional mediators of inflammation are released.

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where do ICs deposit?

depends on size and charge

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complement levels in SLE

the lower the complement (C3/4), the higher the disease activity because consumption indicates IC clearing

36

cytokines important in lupus

Interferon and BLyS

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TLRs of SLE

7/9. activated by ICs to stimulate dendritic cells, which then release type 1 interferons

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type 1 IFNs

first responder to infection, potent promoter of inflammatory response and promotes survival of auto reactive B cells. higher level=increased disease activity

39

BLyS (BAFF)

B lymphocyte stimulator, promotes increase B cell survival.

40

anti-BLyS antibody?

Belimumab (Benlysta). targeted monoclonal antibody that binds to soluble BLyS, allowing more B cells to undergo apoptosis, preventing survival of auto reactive B cells

41

how t cells cause damage in lupus

stimulate autoreactive b cells via cytokines, can also directly damage tissues (CTL)