Lupus Flashcards
this is a systemic autoimmune rheumatic disease. it is characterized by
- chronic inflammation
- immune response, driven by self antigens
- affects multiple organ systems (skin, joints, kidneys, blood cell lines, serial surfaces, brain)
- episodic in nature, flares and remissions
- highly variable in severity
SLE (system lupus erythematous)
true or false: lupus is more prevalent in men
false
what is the cause of SLE?
- genetic deficiencies in the classical complement pathway (e.g. C1q, C1r, C1s, C2 and C4)
- mutations in the TREX1 on the X chromosome (Klinefelter’s syndrome)
- environmental factors (drugs, viral infections, tobacco, UV light)
what is a protective environmental factor against SLE
alcohol
during the initiation stage of SLE, the ______ response targets a highly specific group of self antigens. although this group of _________ does not share common features in healthy cells, these molecules are modified during apoptotic cell death, when they become clustered and structurally modified in apoptotic surface blebs.
autoantibodies
SLE may begin with the activation of ________ (innate/adaptive) immunity
innate
change in binding of antigen in SLE: plasmacytoid dendritic cells (pDCs) produce _____. up regulation of genes induced by ___ is a genetic “signature” in whole blood, peripheral blood cells, skin lesions, synovium and kidneys in SLE patients
IFNs
change in binding of antigen in SLE: __________ and ________ produce IL-12, TNF, BLYS/BAFF
monocytes and macrophages
change in binding of antigen in SLE: lupus phagocytic cells have a decreased ability to clear apoptotic cells and their auto-antigen containing (e.g. DNA/RNA/Rho/La & phospholipid) surface blebs. what is the result of this?
persistance of large quantities of auto antigens
change in binding of antigen in SLE: neutrophils release ________ which become less effective. results in:
- reduced ability of these cells to kill auto reactive T and B cells
- reduced ability to produce transforming growth factor (TGF-beta) needed for the development of regulatory T cells
NK cells
changes in APC (antigen presenting cells) interactions: peripheral naive activated and double-negative B cells not only present antigens but they also secrete these two interleukins which promotes auto reactive B cell survival
IL-6 and IL-10
changes in APC (antigen presenting cells) interactions: in SLE patients, after the peptides bind to the T cell receptor (TCR), T cell signalling is abnormal beginning with the complexing of TCR with FcR gamma rather than the usual CD3. what is the net production because of this?
decreased IL2 (needed for survival of T-lymphocytes and for generation of regulatory T cells) and increase of IL-17
changes in APC (antigen presenting cells) interactions: the change regarding the complexing of TCR with FcR gamma pushes the ________ (innate/adaptive) immune system toward generation of helper T cells (Th1, Thf and Th17) and away from down regulating regulatory T cells
adaptive
what are the two main things that happen with regard to apoptosis and apoptotic cells in SLE
- unique form of apoptosis in a pro-immune context (infections, sunlight, estradiol)
- impaired/delayed clearance of apoptotic cell tissues (C1q deficiency)
what are the signs and symptoms (clinical presentation) of SLE
- women (especially of child bearing age)
- flares
- butterfly rash
- joint pain
- fever
- weight loss
- anemia
*other synmptoms may depend on what organs/tissues are affected
what are some clinical manifestations of SLE if the musculoskeletal system is affected
- polyarthritis
- tendinitis
- joint pain (can lead to ischemic necrosis of the bone)
- myositis
what are some cutaneous clinical manifestations of SLE
- butterfly rash (photosensitivity of sun exposed body parts)
- scaly, red, psoriasis looking red lesions
- recurrent urticaria
- ulcers of mucosa (mouth and nose)
what are some renal manifestations of SLE
- nephritis (asymptomatic - but serious)
- proliferative glomerular damage (if not diagnosed ESRD develops in 2 yrs)
what are some CNS manifestations of SLE
- psychosis
- seizures
- cognition
what are some vascular/cardiac manifestations of SLE
- strokes
- MI
- endocarditis
- myocarditis (Libman sacks)
what are some pulmonary manifestations of SLE
- pleuritis
- interstitial inflammation leading to fibrosis or intra-alveolar hemorrhage
what are some hematologic (blood) manifestations of SLE
- normochromic normocytic anemia
- leukopenia
- lymphopenia
- thrombocytopenia
what are some GI manifestations of lupus
- N/V/D
- diffuse abdominal pain
- elevated AST and ALT if SLE is active
what are some ocular manifestations of SLE
- sicca (dry) syndrome
- conjunctivitis
- retinal vasculiitis
- optic neuritis
